CONTRAINDICATIONS / PRECAUTIONS
General Information
Ketamine is contraindicated in patients with a hypersensitivity to ketamine or any excipients.[43431]
Obtain baseline and periodic liver function tests, including alkaline phosphatase and gamma-glutamyl transferase, in patients receiving ketamine as part of a treatment plan that utilizes recurrent dosing. Recurrent ketamine use is associated with hepatobiliary dysfunction (most often a cholestasis pattern).[43431]
Aneurysm, angina, cardiac disease, coronary artery disease, glaucoma, head trauma, heart failure, hypertension, increased intracranial pressure, increased intraocular pressure, intracranial bleeding, intracranial mass, ocular surgery, ocular trauma, pulmonary hypertension, stroke, thyroid disease, thyrotoxicosis
Ketamine is contraindicated in patients for whom a significant elevation of blood pressure would constitute a serious hazard, such as those with uncontrolled hypertension, aneurysm, thyrotoxicosis, or a history of stroke. Monitor patients with increased intracranial pressure in a setting with frequent neurologic assessments. Use ketamine with great caution in any patient with the potential for increased intracranial pressure, including those with head trauma, intracranial mass lesions or abnormalities, intracranial bleeding, and hydrocephalus. Alternative agents may be preferable in patients with known structural barriers to normal cerebrospinal fluid flow. Similarly, use ketamine with caution in patients with increased intraocular pressure (e.g., glaucoma), ocular trauma, or those undergoing ocular surgery. Ketamine can have direct negative inotropic properties and should be titrated cautiously in patients with poor ventricular function. The sympathomimetic effect of ketamine can produce elevations in blood pressure, heart rate, and cardiac output, which are typically mild-to-moderate. Ketamine increases coronary perfusion, enhancing myocardial contraction and increasing myocardial oxygen consumption. Hence, ketamine should also be used with caution in patients with cardiac disease, especially coronary artery disease (e.g., angina). Ketamine raises pulmonary arterial pressures somewhat more than systemic pressures and may exacerbate preexisting pulmonary hypertension or congestive heart failure. Monitor vital signs and cardiac function during ketamine administration. In addition, cardiac monitoring may be prudent in patients with thyroid disease requiring thyroid replacement therapy. Ketamine-induced hypertension and tachycardia can be attenuated with the administration of a benzodiazepine, a barbiturate, or a synthetic opioid.
Driving or operating machinery
Advise patients to avoid driving or operating machinery within 24 hours of receiving ketamine due to the residual anesthetic effects and potential for drowsiness.
Requires a specialized care setting, requires an experienced clinician
Ketamine administration requires an experienced clinician trained in the use of general anesthetics, airway maintenance, and assisted ventilation as well as requires a specialized care setting where resuscitation equipment is readily available. Continuously monitor vital signs in patients receiving ketamine.
Females, psychosis, schizophrenia
Emergence reactions (e.g., dream-like states, vivid imagery, hallucinations, delirium), sometimes accompanied by confusion, excitement, and irrational behavior may occur during ketamine recovery. Emergence reactions typically last no more than a few hours; however, adverse psychiatric events have occurred and/or persisted days to weeks after ketamine exposure. Incidence can be reduced by using lower recommended doses of ketamine in conjunction with an intravenous benzodiazepine during anesthesia, as well as minimizing verbal, tactile, and visual patient stimulation during recovery. Emergence reactions appear to be less common with intramuscular administration. Reported risk factors include age older than 10 years, females, rapid intravenous administration, preexisting psychosis (e.g., schizophrenia), or patients who normally dream frequently. The use of alternative agents is recommended for procedural sedation in patients with a history of psychosis. Strong psychological factors appear to influence the severity; avoid ketamine in hallucination-prone individuals. Upsetting reactions are much less common in children 10 to 15 years compared to adults and are rare in children younger than 10 years, presumably because a naive child with few life experiences is less likely to interpret unusual dreams or hallucinations as unpleasant. For older children and adults, advanced planning of a pleasant topic to dream about may decrease the incidence of a distressing reaction.
Substance abuse
Ketamine has the potential for substance abuse, psychological dependence, and/or criminal diversion. Illicit use of ketamine for its psychological effects (i.e., similar to PCP) and 'date rape' use due to its amnestic effects have been reported. Physical dependence, tolerance, and a withdrawal syndrome may occur with long-term use.
Porphyria
The use of ketamine in patients with porphyria is controversial due to contradictory evidence. Many experts consider ketamine anesthesia safe in porphyria patients; safe use in dormant acute intermittent porphyria and hereditary coproporphyria crisis have been reported. Most animal and cell culture models suggest it is non-inducing at clinical concentrations. However, increases in delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and other porphyrins after ketamine anesthesia have been reported and some experts consider porphyria a relative contraindication to its use.
Head and neck anesthesia, infants, neonates, pulmonary disease, respiratory infection
Avoid ketamine as a sole agent for head and neck anesthesia during procedures of the pharynx, larynx, or bronchial tree, including mechanical stimulation of the pharynx; muscle relaxants may be required. Ketamine does not suppress pharyngeal and laryngeal reflexes.[43431] Clinicians using ketamine for procedures involving the pharynx (e.g., endoscopy) should make every effort to avoid vigorous stimulation of the posterior pharynx while still preventing accumulation of secretions or blood in the area.[57147] Neonates and infants younger than 3 months have a higher incidence of ketamine-induced respiratory complications (e.g., laryngospasm, apnea, coughing spells, aspiration), most likely attributable to differences in airway anatomy and age-associated laryngeal excitability. Because of these age-related differences, avoid ketamine in non-intubated patients younger than 3 months and use with caution in those younger than 1 year. Ketamine use is relatively contraindicated in patients with an unsupported airway who have a history of airway instability, tracheal surgery, tracheal stenosis, tracheomalacia, laryngomalacia, pulmonary disease, or an acute pulmonary infection including upper respiratory infection.[41115] [45333] [56732] [57147] Ketamine can increase oral secretions, influencing airway patency and further compromising respiratory function, particularly in unsupported patients. Administration of an anticholinergic prior to or concurrently with ketamine may help limit secretions; however, prophylaxis is not routinely recommended during procedural sedation.[41115] [43431] [45333] [56732] [57147] Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in pediatric patients younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in a young child against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.[61572]
Children
Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in neonates, infants, and children younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.[61572] Animal data has suggested ketamine can induce apoptosis when administered in high doses or for prolonged periods. Neurotoxicity in the developing brain may correlate to learning and behavioral abnormalities later in life. Concern about potential human neurotoxicity has prompted investigation, but current evidence is lacking.[57147] [57152] Results from a small prospective study conducted in 49 young pediatric patients (3 to 22 months, ASA I) undergoing outpatient laser surgery have suggested that repeated exposure to anesthetic ketamine has the potential to negatively impact neurodevelopment. In the study, Bayley Scales of Infant Development-Second Edition scores, a tool used to predict neurodevelopmental outcomes after surgery, were significantly lower after the third exposure to ketamine (each dose = 8 mg/kg IM) compared to baseline in the group with 3 total exposures. In addition, concentrations of the S100B protein were significantly higher after the last procedure compared to baseline in groups with 1, 2, and 3 exposures; elevation of this protein in blood reliably occurs in clinical scenarios associated with central nervous system (CNS) injury.[60974] Although the study designs were much different, these results conflict with those from a study evaluating 24 infant patients treated randomly with either a single dose of ketamine 2 mg/kg IV or placebo prior to cardiopulmonary bypass surgery for ventricular septal defect repair, where no significant differences in markers of CNS injury (including S100B expression and Bayley scores) were noted after ketamine exposure.[60975]
Geriatric
In general, dose selection for a geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Labor, obstetric delivery, pregnancy
Ketamine administration is not recommended during pregnancy, labor, or obstetric delivery because safe use has not been established. Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures during the third trimester of pregnancy may have negative effects on fetal brain development. Consider the benefits of appropriate anesthesia in pregnant women against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required prior to delivery. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child and/or mother. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.
Breast-feeding
Use ketamine with careful monitoring in breast-feeding mothers; alternate agents are preferred. Minimal data indicate that ketamine use in breast-feeding mothers may not affect the breast-fed infant or lactation.
DRUG INTERACTIONS
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of dihydrocodeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Acetaminophen; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Acetaminophen; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Acrivastine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Alfentanil: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when alfentanil is given concurrently with ketamine. Monitor for CNS depression, hypotension, and respiratory depression during use together. Prolonged recovery time may occur. Postoperative confusional states may occur during the recovery period during use of ketamine. The patient should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.
Aliskiren: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
Ambrisentan: (Minor) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with ambrisentan may increase the risk of developing hypotension.
Amikacin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
Amiodarone: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone. For example, when fentanyl was administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl.
Amobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Amoxapine: (Moderate) Because amoxapine can cause sedation, an enhanced CNS depressant effect may occur during combined use with general anesthetics such as enflurane.
Amphetamine; Dextroamphetamine Salts: (Moderate) Closely monitor vital signs when ketamine and amphetamine; dextroamphetamine salts are coadministered; consider dose adjustment individualized to the patient's clinical situation. Amphetamine; dextroamphetamine salts may enhance the sympathomimetic effects of ketamine.
Angiotensin II receptor antagonists: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Angiotensin-converting enzyme inhibitors: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as general anesthetics.
Articaine; Epinephrine: (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Aspirin, ASA; Carisoprodol: (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with ketamine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azelastine: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Azelastine; Fluticasone: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Bacitracin: (Moderate) General anesthetics should be used cautiously in patients receiving systemic bacitracin. Systemic bacitracin may act synergistcally to increase or prolong skeletal muscle relaxation produced by neuromuscular blocking agents and/or general anesthetics. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade.
Baclofen: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
Barbiturates: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Belladonna; Opium: (Major) Concomitant use of opium with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Concomitant administration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
Benzphetamine: (Moderate) Closely monitor vital signs when ketamine and benzphetamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Benzphetamine may enhance the sympathomimetic effects of ketamine.
Beta-adrenergic blockers: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Brompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Bupivacaine Liposomal: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Bupivacaine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Bupivacaine; Epinephrine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
Bupivacaine; Lidocaine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Bupivacaine; Meloxicam: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Buprenorphine: (Major) If general anesthetics are required during treatment with buprenorphine, consider the potential for additive pharmacological effects during dose selection. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) If general anesthetics are required during treatment with buprenorphine, consider the potential for additive pharmacological effects during dose selection. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Monitor patients for sedation or respiratory depression.
Buspirone: (Moderate) General anesthetics potentiate the effects of CNS depressants.
Butabarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Butalbital; Acetaminophen: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Calcium-channel blockers: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ketamine. CNS depressants can potentiate the effects of cannabidiol.
Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
Capsaicin; Metaxalone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Carbinoxamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Carbinoxamine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Carbinoxamine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Carisoprodol: (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cenobamate: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving cenobamate closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Central-acting adrenergic agents: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Cetirizine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Chlophedianol; Dexbrompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorcyclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chloroprocaine: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
Chlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of dihydrocodeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpromazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Chlorzoxazone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Cholinesterase inhibitors: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Clemastine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Potentiation of CNS effects (i.e., increased sedation or respiratory depression) may occur when clobazam is combined with other CNS depressants such as general anesthetics.
Clozapine: (Moderate) Clozapine can potentiate the actions of other CNS depressants such as the general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Codeine; Promethazine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Colistin: (Moderate) General anesthetics 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.
COMT inhibitors: (Major) Additive CNS depression and hypotension may occur when general anesthetics and COMT inhibitors are used together. Monitor patients closely for additive effects that may prolong recovery.
Cyclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Cyproheptadine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dantrolene: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with ketamine due to the potential for increased ketamine exposure which may increase the risk of toxicity. Ketamine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Desloratadine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Dexbrompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dexchlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dexmedetomidine: (Moderate) Coadministration of dexmedetomidine with general anesthetics is likely to lead to an enhancement of anesthetic, sedative, or cardiovascular effects. Due to possible pharmacodynamic interactions, when co-administered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant anesthetic may be required. Specific studies have confirmed these pharmacodynamic effects with sevoflurane, isoflurane, and propofol. No pharmacokinetic interactions between dexmedetomidine and isoflurane or propofol have been demonstrated.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Diethylpropion: (Moderate) Closely monitor vital signs when ketamine and diethylpropion are coadministered; consider dose adjustment individualized to the patient's clinical situation. Diethylpropion may enhance the sympathomimetic effects of ketamine.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Ibuprofen: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Naproxen: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with ketamine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dobutamine: (Moderate) Closely monitor vital signs when ketamine and dobutamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Dobutamine may enhance the sympathomimetic effects of ketamine.
Donepezil; Memantine: (Moderate) Ketamine is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of ketamine with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Dopamine: (Moderate) Closely monitor vital signs when ketamine and dopamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Dopamine may enhance the sympathomimetic effects of ketamine.
Doxazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Doxylamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Doxylamine; Pyridoxine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants like general anesthetics can potentiate the effects of dronabinol on respiratory depression.
Droperidol: (Major) Central nervous system (CNS) depressants (e.g., general anesthetics) have additive or potentiating effects with droperidol. Following administration of droperidol, the dose of the other CNS depressant should be reduced.
Dyphylline: (Moderate) Methylxanthines and inhaled general anesthetics have been associated with adverse cardiovascular effects. Concurrent use may increase the risk of such effects including cardiac arrhythmias.
Dyphylline; Guaifenesin: (Moderate) Methylxanthines and inhaled general anesthetics have been associated with adverse cardiovascular effects. Concurrent use may increase the risk of such effects including cardiac arrhythmias.
Ephedrine: (Moderate) Closely monitor vital signs when ketamine and ephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Ephedrine may enhance the sympathomimetic effects of ketamine.
Ephedrine; Guaifenesin: (Moderate) Closely monitor vital signs when ketamine and ephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Ephedrine may enhance the sympathomimetic effects of ketamine.
Epinephrine: (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
Eplerenone: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Epoprostenol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Esketamine: (Major) Although CNS depression is a desired effect of general anesthetics, patients also receiving esketamine should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic. If possible, avoid scheduling a treatment session with esketamine on the same day that general anesthesia is required. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Eszopiclone: (Moderate) A temporary dose reduction of eszopiclone should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and general anesthetics. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of fentanyl with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Fexofenadine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Gentamicin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
Guaifenesin; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Guaifenesin; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Guaifenesin; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Haloperidol: (Major) Haloperidol can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Hydromorphone: (Major) Concomitant use of hydromorphone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydroxyzine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Ibuprofen; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Iloprost: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ionic Contrast Media: (Moderate) General anesthesia may be indicated in the performance of some procedures in young or uncooperative children and in selected adult patients; however, a higher incidence of adverse reactions has been reported to ionic contrast media in these patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia, which can prolong the circulation time and increase the duration of contact of the contrast agent.
Isoproterenol: (Moderate) Closely monitor vital signs when ketamine and isoproterenol are coadministered; consider dose adjustment individualized to the patient's clinical situation. Isoproterenol may enhance the sympathomimetic effects of ketamine.
Lasmiditan: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Lemborexant: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Levorphanol: (Major) Concomitant use of levorphanol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of respiratory depression and sedation.
Levothyroxine: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Levothyroxine; Liothyronine (Porcine): (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Lidocaine; Epinephrine: (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
Lidocaine; Prilocaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Liothyronine: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Lisdexamfetamine: (Moderate) Closely monitor vital signs when general anesthetics and lisdexamfetamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Lisdexamfetamine may enhance the sympathomimetic effects of general anesthetics.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and ketamine. Lofexidine can potentiate the effects of CNS depressants
Loop diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Lopinavir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with ketamine due to the potential for increased ketamine exposure which may increase the risk of toxicity. Ketamine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Loratadine; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Loxapine: (Moderate) Loxapine can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and general anesthetics. Concurrent use may result in additive CNS depression. Monitor patients closely for additive effects that may prolong recovery after use of a general anesthetic.
Maprotiline: (Moderate) General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
Mecamylamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Meclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Memantine: (Moderate) Ketamine is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of ketamine with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Meperidine: (Major) Concomitant use of meperidine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Meperidine; Promethazine: (Major) Concomitant use of meperidine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Meprobamate: (Moderate) The effects of CNS depressant drugs, such as meprobamate, may increase when administered concurrently with general anesthetics. A temporary dose reduction of meprobamate should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Metaxalone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Methadone: (Moderate) Concomitant use of methadone with another CNS depressant can lead to additive respiratory depression, hypotension, profound sedation, or coma; examples include general anesthetics. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; in opioid-naive adults, use an initial methadone dose of 2.5 mg every 12 hours. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression
Methamphetamine: (Moderate) Closely monitor vital signs when general anesthetics and methamphetamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Methamphetamine may enhance the sympathomimetic effects of general anesthetics.
Methocarbamol: (Moderate) The use of general anesthetics with other CNS depressants, including skeletal muscle relaxants, can potentiate CNS depression and/or increase the risk of developing respiratory depression.
Methohexital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Methylphenidate Derivatives: (Moderate) Closely monitor vital signs when ketamine and methylphenidate derivatives are coadministered; consider dose adjustment individualized to the patient's clinical situation. Methylphenidate derivatives may enhance the sympathomimetic effects of ketamine.
Midodrine: (Moderate) Closely monitor vital signs when ketamine and midodrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Midodrine may enhance the sympathomimetic effects of ketamine.
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 general anesthetics. Caution should be exercised when using these agents concurrently. Additionally, the concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. Use caution when administering other tetracyclines.
Mirtazapine: (Moderate) Consistent with the pharmacology of mirtazapine and the CNS depression that may occur, additive effects may occur with other CNS depressants, including ketamine. Close monitoring is recommended in patients receiving mirtazapine and requiring an anesthetic.
Monoamine oxidase inhibitors: (Major) Discontinue monoamine oxidase inhibitors (MAOIs) at least 10 days prior to elective surgery requiring use of general anesthetics due to the potential for significant hypotension. If this is not possible, carefully consider the risk of agents and techniques (e.g., epidural or spinal anesthesia) that increase the risk for hypotension.
Morphine: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nabilone: (Major) Concomitant use of nabilone with other CNS depressants like general anesthetics can potentiate the effects of nabilone on the central nervous system. Additive drowsiness and CNS depression can occur.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Naproxen; Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
Nirmatrelvir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with ketamine due to the potential for increased ketamine exposure which may increase the risk of toxicity. Ketamine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Norepinephrine: (Moderate) Closely monitor vital signs when ketamine and norepinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Norepinephrine may enhance the sympathomimetic effects of ketamine.
Oliceridine: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general 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.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with ketamine due to the potential for increased ketamine exposure which may increase the risk of toxicity. Ketamine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxymorphone: (Major) Concomitant use of oxymorphone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxytocin: (Major) Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics, especially in those with preexisting valvular heart disease. Cyclopropane, when administered with or without oxytocin, has been implicated in producing maternal sinus bradycardia, abnormal atrioventricular rhythms, hypotension, and increases in heart rate, cardiac output, and systemic venous return. In addition, halogenated anesthetics decrease uterine responsiveness to oxytocics (e.g., oxytocin) and, in high doses, can abolish it, increasing the risk of uterine hemorrhage. Halothane is a potent uterine relaxant. Enflurane displaces the myometrial response curve to oxytocin so that at lower concentrations of enflurane oxytocin will restore uterine contractions. However, as the dose of enflurane progresses (somewhere between 1.5 to 3% delivered enflurane) the response to oxytocin is inhibited. It is not clear if other halogenated anesthetics would interact with oxytocics in this manner.
Papaverine: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Pentobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Phendimetrazine: (Moderate) Closely monitor vital signs when ketamine and phendimetrazine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phendimetrazine may enhance the sympathomimetic effects of ketamine.
Phenobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Phenoxybenzamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Phentermine: (Moderate) Closely monitor vital signs when ketamine and phentermine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phentermine may enhance the sympathomimetic effects of ketamine.
Phentermine; Topiramate: (Moderate) Closely monitor vital signs when ketamine and phentermine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phentermine may enhance the sympathomimetic effects of ketamine.
Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Polymyxin B: (Moderate) Systemic polymyxin B can increase the neuromuscular blockade effects of neuromuscular blockers, general anesthetics, and skeletal muscle relaxants. Polymyxin B affects both pre- and post-synaptic myoneural areas by inhibiting release of acetylcholine pre-synaptically and/or blocking acetylcholine activity post-synaptically. Thus, polymyxin B acts synergistically with these agents.
Potassium-sparing diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Prazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pregabalin: (Major) Concomitant use of general anesthetics with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Prilocaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Prilocaine; Epinephrine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine.
Primidone: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Procaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to procaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Procarbazine: (Major) Patients receiving drugs that possess MAOI properties, such as procarbazine, may have an increased risk of hypotension after administration of general anesthetics. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
Prochlorperazine: (Moderate) Additive CNS effects may occur if prochlorperazine is administered concomitantly with general anesthetics.
Promethazine; Phenylephrine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
Pseudoephedrine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine.
Pseudoephedrine; Triprolidine: (Moderate) Closely monitor vital signs when ketamine and pseudoephedrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Pseudoephedrine may enhance the sympathomimetic effects of ketamine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Racepinephrine: (Moderate) Closely monitor vital signs when ketamine and racepinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Racepinephrine may enhance the sympathomimetic effects of ketamine.
Rasagiline: (Moderate) Patients receiving drugs that possess MAOI properties, such as rasagiline, may have an increased risk of hypotension after administration of general anesthetics, although specific studies are not available. Combined hypotensive effects are also possible with the combined use of MAOIs and spinal anesthetics.
Remifentanil: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when remifentanil is given concurrently with ketamine. Monitor for CNS depression, hypotension, and respiratory depression during use together. Prolonged recovery time may occur. Postoperative confusional states may occur during the recovery period during use of ketamine. The patient should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.
Ritonavir: (Moderate) Use caution if ritonavir is coadministered with ketamine due to the potential for increased ketamine exposure which may increase the risk of toxicity. Ketamine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Secobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Sedating H1-blockers: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Selegiline: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Sotalol: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Streptomycin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
Sufentanil: (Major) Both the magnitude and duration of central nervous system and cardiorespiratory effects may be potentiated when sufentanil is given concurrently with ketamine. Monitor for CNS depression, hypotension, and respiratory depression during use together. Prolonged recovery time may occur. Postoperative confusional states may occur during the recovery period during use of ketamine. The patient should be cautioned that driving an automobile, operating hazardous machinery or engaging in hazardous activities should not be undertaken for 24 hours or more (depending upon the dosage of ketamine and consideration of other drugs employed) after anesthesia.
Suvorexant: (Moderate) CNS depressant drugs, including general anesthetics, may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of either suvorexant or the CNS depressant may be needed in some cases.
Tapentadol: (Major) Concomitant use of tapentadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Terazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Tetracaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to tetracaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
Theophylline, Aminophylline: (Major) Consider using an alternative to ketamine in patients receiving aminophylline; concomitant use may lower the seizure threshold. (Major) Consider using an alternative to ketamine in patients receiving theophylline; concomitant use may lower the seizure threshold.
Thiazide diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Thioridazine: (Moderate) The use of ketamine with other CNS depressants, such as phenothiazines, can potentiate CNS depression and/or increase the risk of developing respiratory depression.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Thyroid hormones: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Tobramycin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
Tramadol: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Treprostinil: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Tricyclic antidepressants: (Moderate) General anesthetics, including ketamine, may generally produce additive CNS depression when used in patients taking tricyclic antidepressants (TCAs). Specific interactions between ketamine and TCAs are not certain.
Triprolidine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Vasodilators: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Vasopressin, ADH: (Moderate) Closely monitor vital signs when ketamine and vasopressin are coadministered; consider dose adjustment individualized to the patient's clinical situation. Vasopressin may enhance the sympathomimetic effects of ketamine.
Zaleplon: (Moderate) Coadministration of zaleplon and general anesthetics may result in additive CNS depressant effects. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. A similar interaction may occur with zaleplon and other CNS depressants including general anesthetics. If concurrent use is necessary, monitor for additive side effects. A temporary dose reduction of zaleplon should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Zolpidem: (Moderate) The effects of CNS depressant drugs, such as zolpidem, may increase when administered concurrently with general anesthetics. A temporary dose reduction of the CNS depressant should be considered following administration of general anesthetics. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.