CONTRAINDICATIONS / PRECAUTIONS
General Information
Lidocaine application to oral mucosa can interfere with swallowing and increase the risk of aspiration. Patients should not ingest food for at least 1 hour after the use of anesthetic agents in the mouth or throat.
Local anesthetics, like lidocaine, should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death.
Amide local anesthetic hypersensitivity, epidural anesthesia
Lidocaine is contraindicated in patients with amide local anesthetic hypersensitivity. Parenteral preparations containing preservatives should not be used for spinal or epidural anesthesia. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. There have been no reports of cross-sensitivity between lidocaine and either procainamide or quinidine.[32857]
Collagen-vascular disease
Lidocaine does not provide adequate anesthesia in patients with collagen-vascular disease, such as Ehlers Danlos Type III. Lidocaine is relatively contraindicated in these conditions.
Cardiac disease, G6PD deficiency, methemoglobinemia, pulmonary disease
Methemoglobinemia has been reported with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), preexisting (congenital or idiopathic) methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), those younger than 6 months, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing methemoglobinemia. Monitor such patients closely for signs and symptoms of methemoglobinemia if a local anesthetic must be used. Signs of methemoglobinemia may occur immediately or may be delayed hours after exposure. Immediately discontinue the local anesthetic to avoid serious central nervous system and cardiovascular adverse events, as methemoglobin concentrations may continue to rise. Patients may require supportive care such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.[43368] [43370] [43383]
Geriatric, heart failure, hepatic disease
Use lidocaine with caution in patients at increased risk of adverse events. Conditions that reduce hepatic blood flow such as hepatic disease and congestive heart failure may reduce hepatic metabolism and lead to drug accumulation, increasing the risk of developing systemic toxicity, particularly with parenteral, prescription topical jelly, or transdermal patch use. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated, particularly by those who are debilitated, pediatric patients, geriatric patients, or the acutely ill. Excessive dosing by applying lidocaine transdermal patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious systemic adverse effects. Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of transdermal application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.
Hypotension, pregnancy
Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women. Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure. When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary. A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.
Breast-feeding
According to the manufacturers, caution should be exercised when lidocaine is administered to breast-feeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breast-feeding women. The American Academy of Pediatrics lists lidocaine as usually compatible with breast-feeding. When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.
Adams-Stokes syndrome, atrial fibrillation, atrial flutter, AV block, bradycardia, cardiogenic shock, hemorrhagic shock, hypovolemia, shock, Wolff-Parkinson-White syndrome
Although specific forms of parenteral lidocaine are indicated for the treatment of some cardiac arrhythmias, it can worsen others. Intravenous (IV) lidocaine for the treatment of ventricular arrhythmias is contraindicated in patients with Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, or with severe SA block, AV block, or intraventricular heart block. The administration of IV lidocaine for the elimination of ventricular ectopic beats to patients with bradycardia or incomplete heart block without prior acceleration of heart rate may cause a more serious ventricular arrhythmia or complete heart block. Lidocaine can increase the ventricular rate in patients with atrial fibrillation or atrial flutter. Use lidocaine with caution in patients with hypovolemia. Monitor blood pressure and the electrocardiogram during IV lidocaine administration. Promptly discontinue the infusion if signs of excessive depression of cardiac conductivity occur, such as prolongation of the PR interval, widening of the QRS interval, or appearance or aggravation of arrhythmias. Use both parenteral and topical formulations of lidocaine with caution in patients with severe shock (including cardiogenic shock and hemorrhagic shock) and heart block. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged AV conduction (i.e., PR or QT prolongation) caused by local anesthetics. Topical ocular application of lidocaine is not expected to result in systemic exposure.
Renal disease, renal failure, renal impairment
No lidocaine dosage adjustment needed in patients with renal impairment. However, the elimination of glycine xylidide (major active metabolite) is eliminated renally, and accumulation of the metabolite in severe renal failure (renal disease) theoretically could result in neurotoxicity.
Burns, eczema, heating pad, occlusive dressing, skin abrasion
Applying dermal, transdermal, or oromucosal lidocaine preparations to severely traumatized skin (e.g., mucosal or skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., exercise, or application of thermal heat wraps or a heating pad immediately before or during topical lidocaine use) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of lidocaine or using an occlusive dressing (skin wraps) can increase absorption. Topical burn pads may be applied over burns and covered with tape or gauze while avoiding application of large quantities, particularly over raw surfaces or blistered areas. Patches and administration via Zingo injection system should only be used on intact skin, and transoral delivery systems should only be applied to intact mucosa. Excessive dosing by applying patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine. Application of one additional Zingo at a new location is acceptable after a failed attempt at venous access. However, multiple administrations of Zingo at the same location are not recommended. Multiple Zingo applications could result in plasma concentrations that could produce systemic toxicity. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly, and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.
Cataracts, ocular exposure, ocular trauma
Avoid unintended ocular exposure of lidocaine dermal, oromucosal, and transdermal products. Severe eye irritation has been reported in animals treated with similar products. If eye contact occurs, immediately wash the eye with water or saline and protect the eye until sensation returns. Lidocaine ophthalmic gel is intended for application to the eye surface under the direct supervision of a health care provider; it is NOT intended for patient self-administration. Prolonged use may produce permanent corneal opacification and ulceration with accompanying visual loss. Use with caution in patients with pre-existing cataracts or ocular trauma or ulceration.
Accidental exposure
To avoid accidental exposure and/or ingestion, advise patients and/or their caregivers to store and dispose of all lidocaine products out of the reach of any pediatric-age person and pets. It is important to note that whether new or used, lidocaine patches contain a large amount of lidocaine (at least 665 mg post-use). The potential exists for small kids or pets to suffer serious adverse reactions from unintended lidocaine exposure including chewing or ingesting a new or used lidocaine patch.
Intraarterial administration, intrathecal administration, intravenous administration
When parenteral lidocaine is intended as a local anesthetic, avoid intravenous administration, intraarterial administration, or intrathecal administration. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. Further, do not administer preservative-containing parenteral lidocaine via intrathecal routes. To avoid intravascular administration of lidocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. During epidural administration, a test dose should be administered initially and the patient should be monitored for CNS and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration (see Adverse Reactions). Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.
Head and neck anesthesia
Patients receiving local head and neck anesthesia including retrobulbar, stellate ganglion, and dental blocks, are at increased risk of CNS toxicity similar to the systemic toxicity seen with unintentional intravascular injections of large doses of lidocaine. These reactions may be due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.
Ocular surgery
When local anesthetics, like lidocaine, are used for retrobulbar block during ocular surgery, lack of corneal sensation should not be relied upon to determine whether or not the patient is ready for surgery. Lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.
Anticoagulant therapy, bleeding, coagulopathy, infection, neurological disease, requires a specialized care setting, requires an experienced clinician, sepsis, spinal anesthesia, thrombocytopenia
Parenteral use of lidocaine requires an experienced clinician and requires a specialized care setting. Lidocaine preparations containing preservatives should not be used for epidural or spinal anesthesia. Patients with the following conditions should receive spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis; pediatric patients younger than 16 years, or elderly patients; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard textbooks for specific techniques and precautions for spinal anesthetic procedures. Epidural, local, nerve block and spinal administration of lidocaine are contraindicated in patients with the following: infection or inflammation at the injection site, bacteremia (sepsis), platelet abnormalities, thrombocytopenia less than 100,000/mm3, increased bleeding time, uncontrolled coagulopathy or bleeding, or anticoagulant therapy. Lumbar and caudal epidural anesthesia should be used with extreme caution in patients with existing neurological disease, spinal deformities, sepsis, and severe hypertension. Use caution when applying topical lidocaine to mucous membranes in the presence of sepsis due to the potential for rapid systemic absorption. Patients with platelet disorders or those with bleeding tendencies may be at risk for superficial dermal bleeding when lidocaine is administered intradermally for topical anesthesia.
Fetal distress, labor, obstetric delivery, pudendal nerve block
During labor and obstetric delivery, local anesthetics, like lidocaine, can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Appropriate patient positioning during obstetric delivery may decrease maternal hypotension that can result from regional anesthesia. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, spinal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Electronic fetal monitoring for signs of fetal distress is highly recommended.
Continuous intraarticular infusion administration
Lidocaine is not approved for continuous intraarticular infusion administration. Infusion of local anesthetics into a joint space may have caused chondrolysis. Local anesthetics are not indicated for continuous intraarticular postoperative infusions or for use with infusion devices such as elastomeric pumps.
Fetal prematurity, paracervical nerve block
Physicians should weigh the possible risks versus benefits when considering obstetrical paracervical nerve block with parenteral lidocaine in situations of fetal prematurity, toxemia of pregnancy, and fetal distress. Adherence to the recommended dosage is critical during obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. The recommended dose of the local anesthetic should not be exceeded. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between administration to each side.
Malignant hyperthermia
Use lidocaine with caution in patients with a genetic predisposition to malignant hyperthermia. Although it is unknown whether lidocaine triggers this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments.
Children, infants, neonates, teething pain
Lidocaine dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition. When multiple formulations of lidocaine are used at once, the amount systemically absorbed from all formulations must be considered. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated by pediatric patients, particularly by those who are debilitated or the acutely ill. Similar increases in systemic exposure are possible with repeat topical application. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients. Non-prescription (OTC) products should not be used without healthcare professional advice in those under 2 years of age, or as directed on the product label. Do not use lidocaine viscous solution for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death. The FDA reviewed 22 cases of serious adverse events that occurred in infants and young children between 5 months and 3.5 years of age after receiving lidocaine viscous solution for the treatment of mouth pain due to teething or stomatitis or who had accidental ingestions. Of the 22 cases, 6 cases resulted in death, 3 were categorized as life-threatening, 11 required hospitalization, and 2 required medical intervention without hospitalization. The FDA recommends against the use of topical pain relievers for teething pain due to the fact that they wash out of the mouth within minutes of application and can cause serious adverse reactions if they are swallowed in excessive amounts. Advise parents and caregivers with teething pain concerns to follow the American Academy of Pediatrics recommendations for the management of teething pain, which include using a teething ring chilled in the refrigerator (not frozen) and gently rubbing or massaging the gums with a finger. For other conditions, the use of viscous lidocaine in neonates, infants, and children 3 years of age and younger should be limited to those situations where safer alternatives are not available or have failed. To ensure safety, doses should be measured by an accurate device, administered no more often than every 3 hours, used only for the prescribed indication, and stored safely out of the reach of children immediately after use. When topical anesthetics are used in the mouth, the topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.
DRUG INTERACTIONS
Acebutolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Codeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Dextromethorphan: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Diphenhydramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Hydrocodone: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Ibuprofen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Oxycodone: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Pentazocine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Adagrasib: (Moderate) Monitor for lidocaine toxicity if coadministration with adagrasib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Adapalene; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Aldesleukin, IL-2: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
Alfentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Ambenonium Chloride: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Coadministration of lidocaine with oxidizing agents, such as aminosalicylic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Amiodarone: (Major) Concomitant administration of lidocaine with amiodarone has been reported to cause sinus bradycardia and seizure. Amiodarone and its main metabolite, N-monodesethylamiodarone (DEA), appear to inhibit the metabolism of lidocaine by competitively inhibiting CYP3A4. Furthermore, DEA inhibits lidocaine metabolism in a concentration-dependent manner. Also, the metabolism of amiodarone to DEA appears to be competitively inhibited by lidocaine. Close correlations between amiodarone N-monodesethylase activities and the amounts of CYP3A4 and the rates of lidocaine N-monodesethylation have been observed from analyses of in vitro data. Inhibition of lidocaine metabolism is supported by in vivo data from 6 adults. The mean systemic concentration of lidocaine over 300 minutes after receipt of lidocaine hydrochloride 1 mg/kg intravenously before amiodarone treatment is 111.7 +/- 23.2 mcg/minute/mL. In contrast, the mean systemic concentration of lidocaine over 300 minutes after cumulative amiodarone doses of 3 g and 13 g is 135.3 +/- 34.6 and 131.7 +/- 25.5 mcg/minute/mL, respectively. As expected, the systemic exposure of the lidocaine metabolite, monoethylglycinexylidide, decreases from 19.2 +/- 6.5 to 15.8 +/- 8.3 mcg/minute/mL after 3 g of amiodarone. In addition, the systemic clearance of lidocaine decreases from 7.86 +/- 1.83 to 6.31 +/- 2.21 mL/minute/kg body weight. As compared with values before amiodarone administration, the lidocaine elimination half-life and the distribution volume at steady state remain relatively unchanged. Due to the long half-life of amiodarone, clinicians should use caution when administering lidocaine to patients who are receiving or who have recently discontinued amiodarone.
Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Atorvastatin: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Benazepril: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Celecoxib: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Olmesartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Valsartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
Amyl Nitrite: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Anagrelide: (Moderate) Anagrelide has been shown to inhibit CYP1A2. In theory, coadministration of anagrelide with substrates of CYP1A2, including lidocaine, could lead to increases in the serum concentrations of lidocaine and, thus, adverse effects. Patients receiving anagrelide and lidocaine concomitantly should be monitored for increased toxicity of lidocaine.
Apalutamide: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with apalutamide is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Major) Use caution if lidocaine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in lidocaine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. This interaction is not expected with topical preparations of lidocaine. Lidocaine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of systemic lidocaine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. (Moderate) Use articaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Asciminib: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aspirin, ASA; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Atazanavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Atazanavir; Cobicistat: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity. (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Atenolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Atenolol; Chlorthalidone: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Atropine; Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Avacopan: (Moderate) Monitor for lidocaine toxicity if coadministration with avacopan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and avacopan is a weak CYP3A inhibitor.
Belladonna; Opium: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Belumosudil: (Moderate) Monitor for lidocaine toxicity if coadministration with belumosudil is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor.
Bendroflumethiazide; Nadolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Benzalkonium Chloride; Benzocaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzocaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzocaine; Butamben; Tetracaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Clindamycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Erythromycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Sulfur: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Berotralstat: (Moderate) Monitor for lidocaine toxicity if coadministration with berotralstat is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor.
Beta-adrenergic blockers: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Betaxolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Bexarotene: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
Bicalutamide: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Bisoprolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Brimonidine; Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Bupivacaine Liposomal: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Calamine; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Cannabidiol: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Capmatinib: (Moderate) Monitor for an increase in lidocaine-related adverse reactions if coadministration with capmatinib is necessary. Monitor lidocaine concentrations if clinically indicated and lidocaine is being given intravenously. Lidocaine is a CYP1A2 substrate and capmatinib is a weak CYP1A2 inhibitor. Concomitant use may increase lidocaine exposure.
Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
Carbamazepine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes.
Carteolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Carvedilol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Ceritinib: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
Chloramphenicol: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
Chlordiazepoxide; Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Chloroprocaine: (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroquine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as chloroquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroxylenol; Hydrocortisone; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Chlorpheniramine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlorpheniramine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cholinesterase inhibitors: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Cimetidine: (Moderate) Concomitant use of systemic lidocaine and cimetidine may increase lidocaine plasma concentrations. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP1A2 and CYP3A4 substrate; cimetidine inhibits both of these isoenzymes. Concomitant use of lidocaine with a weak CYP1A2 and CYP3A4 inhibitor has reportedly increased lidocaine plasma concentrations by 24% to 75%.
Ciprofloxacin: (Moderate) Concomitant use of systemic lidocaine and ciprofloxacin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ciprofloxacin inhibits both of these isoenzymes. In a study of healthy volunteers (n = 9), concomitant use of lidocaine (1.5mg/kg IV) and ciprofloxacin (500 mg twice daily) resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Citalopram: (Moderate) Concomitant use of systemic lidocaine and citalopram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; citalopram is a weak CYP1A2 inhibitor.
Clarithromycin: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
Clomipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Cobicistat: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Phenylephrine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Colesevelam: (Moderate) Colesevelam may decrease the absorption of lidocaine. To minimize potential for interactions, consider administering lidocaine at least 1 hour before or at least 4 hours after colesevelam.
Colistin: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Conivaptan: (Moderate) Monitor for lidocaine toxicity if coadministration with conivaptan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for lidocaine-related adverse reactions and toxicities if coadministration with crizotinib is necessary. Lidocaine is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclophosphamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as cyclophosphamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Cyclosporine: (Moderate) Concomitant use of systemic lidocaine and cyclosporine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; cyclosporine inhibits CYP3A4.
Dabrafenib: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
Dalfopristin; Quinupristin: (Moderate) Coadministration of lidocaine with dalfopristin; quinupristin may result in elevated lidocaine plasma concentrations. If these drugs are used together, closely monitor for signs of lidocaine-related adverse events. Lidocaine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
Dapsone: (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Daratumumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Darunavir: (Major) Darunavir can inhibit CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and darunavir should be carefully monitored due to the potential for serious toxicity.
Darunavir; Cobicistat: (Major) Darunavir can inhibit CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and darunavir should be carefully monitored due to the potential for serious toxicity. (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Darunavir can inhibit CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and darunavir should be carefully monitored due to the potential for serious toxicity. (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Deferasirox: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
Delavirdine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as lidocaine, should be expected with concurrent use of delavirdine.
Desipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Dexamethasone: (Moderate) Concomitant use of systemic lidocaine and dexamethasone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dexamethasone induces CYP3A4.
Dextromethorphan; Quinidine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
Dibucaine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Diltiazem: (Moderate) Concomitant use of systemic lidocaine and diltiazem may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; diltiazem inhibits CYP3A4.
Disopyramide: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
Disulfiram: (Moderate) Concomitant use of systemic lidocaine and disulfiram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; disulfiram inhibits CYP1A2.
Dofetilide: (Contraindicated) Concurrent exposure of systemic lidocaine with dofetilide could increase the risk of dofetilide-induced proarrhythmias. Before switching from lidocaine to dofetilide therapy, lidocaine generally should be withheld for at least three half-lives prior to initiating dofetilide. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
Donepezil: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Donepezil; Memantine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Dorzolamide; Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Doxepin: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Dronedarone: (Moderate) Concomitant use of systemic lidocaine and dronedarone may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; dronedarone inhibits CYP3A4.
Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Efavirenz: (Moderate) Efavirenz induces cytochrome P450 (CYP) 3A4 and thus, may decrease serum concentrations of lidocaine. Caution is recommended when administering efavirenz with CYP3A4 substrates that have a narrow therapeutic range (e.g., systemic lidocaine).
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces cytochrome P450 (CYP) 3A4 and thus, may decrease serum concentrations of lidocaine. Caution is recommended when administering efavirenz with CYP3A4 substrates that have a narrow therapeutic range (e.g., systemic lidocaine).
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces cytochrome P450 (CYP) 3A4 and thus, may decrease serum concentrations of lidocaine. Caution is recommended when administering efavirenz with CYP3A4 substrates that have a narrow therapeutic range (e.g., systemic lidocaine).
Elagolix: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Elbasvir; Grazoprevir: (Moderate) Administering lidocaine with elbasvir; grazoprevir may result in elevated lidocaine plasma concentrations. Lidocaine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Enzalutamide: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with enzalutamide is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Eslicarbazepine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
Esmolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Ethotoin: (Moderate) Lidocaine is a substrate for the cytochrome P450 isoenzymes 1A2 and 3A4. Ethotoin may enhance lidocaine clearance by inducing cytochrome P-450 enzymes.
Ethyl Chloride: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Etravirine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
Everolimus: (Moderate) Monitor for lidocaine toxicity if coadministration with everolimus is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor.
Famotidine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Felbamate: (Moderate) Concomitant use of systemic lidocaine and felbamate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; felbamate induces CYP3A4.
Fentanyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for epidural analgesia or additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Flecainide: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Fluconazole: (Moderate) Concomitant use of systemic lidocaine and fluconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluconazole inhibits CYP3A4.
Fluoxetine: (Moderate) Concomitant use of systemic lidocaine and fluoxetine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluoxetine inhibits CYP3A4.
Flutamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Fluvoxamine: (Moderate) Concomitant use of systemic lidocaine and fluvoxamine increases lidocaine exposure by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine plasma clearance is decreased by 41% to 60% and the mean half-life prolonged by 1 hour when used in combination with fluvoxamine. Lidocaine is a CYP1A2 and CYP3A4 substrate; fluvoxamine inhibits both of these hepatic isoenzymes.
Food: (Major) Advise patients to avoid cannabis use during lidocaine treatment due to decreased exposure of lidocaine which may alter its efficacy. Cannabis use induces CYP1A2 and lidocaine is a CYP1A2 substrate. The induction potential of cannabis is greatest with chronic inhalation. Other routes of administration or sporadic use may have less of an effect.
Fosamprenavir: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Moderate) Concomitant use of systemic lidocaine and fosphenytoin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; fosphenytoin induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as fosphenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Galantamine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Homatropine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Ibuprofen: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocortisone; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Hydromorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydroxyurea: (Moderate) Coadministration of lidocaine with oxidizing agents, such as hydroxyurea, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ibuprofen; Famotidine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Ibuprofen; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as ifosfamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Imatinib: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate.
Imipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Indinavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Isoniazid, INH: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4. (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
Isoniazid, INH; Rifampin: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4. (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Isosorbide Mononitrate: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Itraconazole: (Moderate) Concomitant use of systemic lidocaine and itraconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; itraconazole inhibits CYP3A4.
Ketoconazole: (Moderate) Concomitant use of systemic lidocaine and ketoconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ketoconazole inhibits CYP3A4.
Labetalol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
Lapatinib: (Major) Monitor for lidocaine toxicity if coadministration with lapatinib is necessary. Concomitant use of systemic lidocaine and lapatinib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Lidocaine is a CYP3A4 substrate and lapatinib is a weak CYP3A4 inhibitor.
Lenacapavir: (Moderate) Monitor for lidocaine toxicity if coadministration with lenacapavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Leniolisib: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lesinurad: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
Lesinurad; Allopurinol: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
Letermovir: (Moderate) An increase in the plasma concentration of lidocaine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Lidocaine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Levobetaxolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Levobunolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Levoketoconazole: (Moderate) Concomitant use of systemic lidocaine and ketoconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ketoconazole inhibits CYP3A4.
Levorphanol: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lidocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lidocaine; Prilocaine: (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lonafarnib: (Moderate) Monitor for lidocaine toxicity if coadministration with lonafarnib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Mafenide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Maribavir: (Moderate) Monitor for lidocaine toxicity if coadministration with maribavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and maribavir is a weak CYP3A inhibitor.
Menthol; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Meperidine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Meperidine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Mepivacaine: (Moderate) Use mepivacaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Methadone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Metoclopramide: (Moderate) Coadministration of lidocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metoprolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Mexiletine: (Major) Mexiletine is chemically and pharmacologically similar to lidocaine; cardiac and toxic effects may be additive. In addition, concurrent use may increase plasma lidocaine concentrations due to the displacement of lidocaine from tissue binding sites by mexiletine. If used together, monitor lidocaine plasma concentrations and adjust the dosage as required.
Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
Mitotane: (Major) Use caution if mitotane and lidocaine are used concomitantly, and monitor for decreased efficacy of lidocaine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and lidocaine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of lidocaine.
Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Modafinil: (Moderate) Concomitant use of systemic lidocaine and modafinil may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; modafinil induces both isoenzymes.
Monoamine oxidase inhibitors: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Morphine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nadolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Nebivolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Nebivolol; Valsartan: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Nefazodone: (Moderate) Concomitant use of systemic lidocaine and nefazodone may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; nefazodone inhibits CYP3A4.
Nelfinavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Neostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Concomitant use of systemic lidocaine and netupitant may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; inhibition of CYP3A4 by netupitant can last for multiple days after a single dose.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nevirapine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval. Systemic lidocaine has been established to have a causal association with QT prolongation and torsade de pointes. Additionally, nilotinib is a moderate CYP3A4 inhibitor and lidocaine is a CYP3A4 substrate; administering these drugs together may result in increased lidocaine levels. If the use of lidocaine is required, hold nilotinib therapy. If the use of nilotinib and lidocaine cannot be avoided, a lidocaine dose reduction may be necessary; close monitoring of the QT interval is recommended.
Nirmatrelvir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Nitrates: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitrofurantoin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrofurantoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitroglycerin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nortriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as lidocaine. Lidocaine is extensively metabolized in the liver into two active compounds, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4. Therapeutic monitoring is recommended with coadministration.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of systemic lidocaine and fluoxetine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluoxetine inhibits CYP3A4.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Concomitant use of systemic lidocaine and rifabutin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; rifabutin induces CYP3A4.
Oritavancin: (Moderate) Lidocaine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of lidocaine may be reduced if these drugs are administered concurrently.
Osilodrostat: (Moderate) Monitor for lidocaine toxicity if coadministration with osilodrostat is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 and CYP3A4 substrate; osilodrostat is a moderate CYP1A2 inhibitor and weak CYP3A4 inhibitor.
Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxymorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Pacritinib: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
Palbociclib: (Moderate) Concomitant use of systemic lidocaine and palbociclib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; palbociclib inhibits CYP3A4.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
Peginterferon Alfa-2b: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
Penbutolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as lidocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as lidocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Perindopril; Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Perphenazine; Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Pertuzumab; Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Phenelzine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Phenobarbital: (Moderate) Concomitant use of systemic lidocaine and phenobarbital may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of systemic lidocaine and phenobarbital may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Phentermine; Topiramate: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4.
Phenytoin: (Moderate) Concomitant use of systemic lidocaine and phenytoin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenytoin induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Physostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Pindolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Pirtobrutinib: (Moderate) Monitor for lidocaine toxicity if coadministration with pirtobrutinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and pirtobrutinib is a weak CYP3A inhibitor.
Posaconazole: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events.
Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Pramoxine; Zinc Acetate: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
Prilocaine: (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primaquine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as primaquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primidone: (Moderate) Concomitant use of systemic lidocaine and primidone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital, the active metabolite of primidone, induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Procainamide: (Major) Concurrent use of systemic lidocaine and other antiarrhythmic drugs such as procainamide may result in additive or antagonistic cardiac effects and additive toxicity. Patients receiving more than one antiarrhythmic drug must be carefully monitored; dosage reduction may be necessary.
Procarbazine: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
Propafenone: (Major) There is limited experience with the use of propafenone with Class IB antiarrhythmics. No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, the concomitant use of propafenone and lidocaine has been reported to increase the risks of central nervous system side effects of lidocaine. When propafenone is coadministered, the dose of lidocaine should be titrated to the desired therapeutic effects.
Propofol: (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
Propranolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Protriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Pyridostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Quinidine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
Quinine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ranolazine: (Major) Ranolazine is an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A, and lidocaine is a substrate for this pathway. Thus, ranolazine may theoretically reduce lidocaine clearance. If concurrent therapy with ranolazine is necessary, administer lidocaine parenteral infusions with caution and monitor lidocaine serum concentrations.
Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Rasburicase: (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Remifentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Ribociclib: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with ribociclib is necessary. Lidocaine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with ribociclib is necessary. Lidocaine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifabutin: (Moderate) Concomitant use of systemic lidocaine and rifabutin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; rifabutin induces CYP3A4.
Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
Rifapentine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Rivastigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Ropivacaine: (Moderate) Use lidocaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rucaparib: (Moderate) Monitor for an increase in lidocaine-related adverse reactions if coadministration with rucaparib is necessary. Lidocaine is a CYP1A2 substrate and rucaparib is a moderate CYP1A2 inhibitor. Coadministration may increase lidocaine plasma concentrations.
Saquinavir: (Contraindicated) The concurrent use of systemic lidocaine and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used together may result in large increases in lidocaine serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as lidocaine.
Selpercatinib: (Moderate) Monitor for lidocaine toxicity if coadministration with selpercatinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and selpercatinib is a weak CYP3A4 inhibitor.
Simeprevir: (Moderate) Simeprevir, a mild CYP1A2 inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of lidocaine, which is a CYP1A2 and CYP3A4 substrate. Monitor patients for adverse effects of lidocaine, such as CNS and cardiovascular effects.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with taurursodiol is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and taurursodiol is a CYP1A2 inducer.
Spironolactone: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
St. John's Wort, Hypericum perforatum: (Moderate) Concomitant use of systemic lidocaine and St. John's Wort may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; St. John's Wort induces CYP3A4.
Streptogramins: (Moderate) Coadministration of lidocaine with dalfopristin; quinupristin may result in elevated lidocaine plasma concentrations. If these drugs are used together, closely monitor for signs of lidocaine-related adverse events. Lidocaine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sufentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Sulfadiazine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfasalazine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfonamides: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tacrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Telmisartan; Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
Teriflunomide: (Moderate) As teriflunomide is a weak inducer of CYP1A2, exposure to lidocaine, a CYP1A2 substrate, may be reduced. Caution should be exercised with concurrent use. Patients should be monitored for loss of antiarrhythmic effect if teriflunomide therapy is initiated. Conversely, lidocaine doses may need adjustment if teriflunomide treatment is discontinued.
Tetracaine: (Moderate) Use tetracaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ticagrelor: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4.
Ticlopidine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Tipranavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
Topiramate: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4.
Tramadol; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Trandolapril; Verapamil: (Moderate) Concomitant use of systemic lidocaine and verapamil may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; verapamil inhibits both hepatic isoenzymes.
Tranylcypromine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Tretinoin; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Tricyclic antidepressants: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Trimipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
Trofinetide: (Moderate) Monitor for lidocaine toxicity if coadministration with trofinetide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Moderate) Monitor for lidocaine toxicity if coadministration with tucatinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of lidocaine with oxidizing agents, such as valproic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Verapamil: (Moderate) Concomitant use of systemic lidocaine and verapamil may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; verapamil inhibits both hepatic isoenzymes.
Viloxazine: (Moderate) Monitor for lidocaine toxicity if coadministration with viloxazine is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 and CYP3A substrate and viloxazine is a strong CYP1A2 and weak CYP3A inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Vonoprazan; Amoxicillin: (Moderate) Monitor for lidocaine toxicity if coadministration with vonoprazan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4. (Moderate) Monitor for lidocaine toxicity if coadministration with vonoprazan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with voriconazole is necessary. Lidocaine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Monitor for lidocaine toxicity if coadministration with voxelotor is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lidocaine.