CONTRAINDICATIONS / PRECAUTIONS
General Information
Caffeine with sodium benzoate injection is not recommended for use in premature neonates because the benzoate may displace bilirubin and induce kernicterus. Elevated serum concentrations of benzoate, similar to benzyl alcohol, have also been associated with neurological disturbances, hypotension, gasping respiration, and metabolic acidosis (i.e., 'gasping syndrome') in neonates. Clinicians should use Cafcit, which does not contain sodium benzoate, or use an extemporaneously compounded caffeine citrate injection in newborns and premature neonates. The safety and efficacy of the prescription use of caffeine in neonates and infants for longer than 12 days, prophylaxis of sudden infant death syndrome (SIDS), or for use prior to extubation in mechanically ventilated infants has not been established.
Children
The OTC use of caffeine products is not recommended in children under the age of 12 years.
Anxiety, insomnia, panic disorder, seizure disorder
Caffeine is a central nervous system stimulant. Caffeine should be used cautiously in patients with anxiety disorders and/or panic disorder because it can aggravate these conditions. Patients suffering from insomnia should not consume caffeine, nor should caffeine be consumed prior to retiring because it can cause insomnia. In overdoses, caffeine has been associated with seizures and it should be prescribed cautiously to those patients with a seizure disorder.
Cardiac arrhythmias, cardiac disease, hypertension, myocardial infarction
Caffeine should be used cautiously in those patients, including neonates, with cardiac disease. Caffeine can stimulate the force of contraction and can increase heart rate. It may increase left ventricular output and stroke volume. Patients who have angina or a history of cardiac arrhythmias should not receive or should minimize their intake of caffeine. Caffeine should not be taken in the first few days—weeks after a myocardial infarction. Patients with hypertension should minimize their intake of caffeine.
Hepatic disease, premature neonates, renal impairment
Caffeine should be used cautiously in those with hepatic disease or hepatic impairment. Caffeine clearance may be delayed, leading to toxicity. Renal impairment or renal failure may also delay caffeine clearance. It should be noted that caffeine elimination is more dependent on renal clearance in premature neonates and term neonates than in older infants or adults, due to the underdeveloped hepatic metabolism and renal elimination of drugs in general. Thus monitoring of serum caffeine concentrations is recommended in neonates or premature neonates, especially those with renal or hepatic impairment.
Diabetes mellitus, hyperglycemia, hypoglycemia
Although the effects are mild, caffeine can either raise or decrease blood sugar; use with caution in patients with diabetes mellitus. In clinical studies reported in the literature, cases of hypoglycemia and hyperglycemia have been observed in neonates receiving caffeine citrate. Therefore, blood glucose may need to be periodically monitored in infants receiving caffeine citrate.
Thyroid disease
Patients with thyroid disease, especially hyperthyroidism, should not receive or should minimize their intake of caffeine. The stimulatory effects of caffeine can be augmented in hyperthyroidism.
Gastroesophageal reflux disease (GERD), necrotizing enterocolitis
In neonates, there are reports in the literature suggesting a possible association between the use of methylxanthines like caffeine and the development of necrotizing enterocolitis. In a clinical trial (n = 85 neonates) evaluating the use of caffeine citrate in apnea of prematurity, necrotizing enterocolitis was reported in 6 patients, 5 of whom were administered caffeine. Three of the infants died. In a much larger clinical trial (n = 2,000 neonates) evaluating the use of caffeine citrate in apnea of prematurity, necrotizing enterocolitis was not more common in caffeine treated patients compared to placebo. Preterm neonates treated with caffeine should be monitored for the development of gastric side-effects (i.e., abdominal distension, vomiting, bloody stools, and lethargy). Caffeine can stimulate gastric secretions and may aggravate gastroesophageal reflux disease (GERD). Clinical trial data are conflicting regarding the limitation of caffeine as an effective strategy to control GERD symptoms; however, recommended lifestyle modifications for patients with GERD often include moderation of caffeine intake.
Infertility, pregnancy
Caffeine citrate is used for neonatal apnea so concerns for teratogenicity are not relevant when administered to infants, however, when 50 mg/kg of sustained-release pellets were administered to pregnant mice during the period of organogenesis, a low incidence of cleft palate and exencephaly have been noted in the fetuses. Caffeine easily crosses the placenta; fetal blood and tissue concentrations approximate maternal concentrations. There are no large, well-controlled studies of caffeine administration in pregnant women; it is generally recommended that the intake of caffeine-containing beverages, like coffee, teas, and sodas, be limited in pregnancy (usually no more than 1 to 2 caffeine-containing beverages/day) or avoided if possible. Caffeine-containing medications should likewise, be limited to use only when absolutely necessary. Low to moderate caffeine intake does not appear to increase the risk of congenital malformation, spontaneous abortion, pre-term birth or low birth weight. The association between high daily intake (more than 500 mg/day) of caffeine and increased rates of low birth weight, spontaneous abortion, difficulty in getting pregnant or infertility is still controversial, as some studies have not controlled for concomitant cigarette smoking. There are no adequate and well-controlled studies of caffeine administration in pregnant women. Neonatal arrhythmias (e.g., tachycardia, premature atrial contractions) and tachypnea have been reported when caffeine was consumed during pregnancy in amounts > 500 mg/day; caffeine withdrawal after birth may account for these symptoms.
Breast-feeding
Although the American Academy of Pediatrics has considered the use of mild to moderate use of caffeinated beverages to be compatible with lactation, mothers who are breast-feeding should limit their intake of caffeinated beverages if possible. Caffeine-containing drug-products should be used cautiously during lactation due to their high caffeine contents. Mothers who are breast-feeding infants who have been prescribed caffeine for apnea should generally avoid additional caffeine use. The CYPP450 hepatic metabolism of caffeine is inhibited in infants who are breastfed; formula feeding does not appear to affect the pharmacokinetics of caffeine in infants. Peak caffeine milk levels usually occur within 1 hour after the maternal ingestion of a caffeinated beverage; with milk: plasma ratios of 0.5 to 0.7 reported. Although only small amounts are secreted in breast milk, caffeine can accumulate in the neonate if maternal ingestion is moderate to high. Higher caffeine intake (more than 500 mg/day) by a nursing mother may cause irritability or poor sleeping patterns in the infant who is breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
Tobacco smoking
Tobacco smoking (cigarettes) has been shown to increase the clearance of caffeine. Passive smoke exposure may also cause an increase in caffeine clearance. This may help to explain why tobacco smokers often have concomitantly high caffeine intakes. Tobacco smoke contains hydrocarbons that induce hepatic CYP450 microsomal enzymes. Because the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco, sudden smoking cessation may result in a reduced clearance of caffeine, despite the initiation of nicotine replacement. Caffeine dosage may need to be reduced at the cessation of smoking.
Geriatric
Caffeine can usually be ingested in normal amounts found in food or beverages (e.g., coffee) in the elderly; however, geriatric patients should be aware of the effects of caffeine on sleep and other physiologic functions, such as urination. Excessive caffeine intake, such as intake of non-prescription caffeine dietary supplements/medicines, should generally be avoided, as excessive use can cause tremor, insomnia, palpitations, and gastrointestinal complaints. Because caffeine is an ingredient in some non-prescription products, patients should be advised to read labels carefully or check with their prescriber or pharmacist if they are unsure if the medication contains caffeine.
MAOI therapy
Caffeine intake should be limited along with MAOI therapy.
DRUG INTERACTIONS
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Acetaminophen; Caffeine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Acetaminophen; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Aclidinium; Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acrivastine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Adenosine: (Major) Larger doses of adenosine may be required or adenosine may not be effective in the presence of methylxanthines. The effects of adenosine are antagonized by methylxanthines. When used for diagnostic purposes, instruct patients to avoid caffeine-containing foods/beverages for at least 5 half-lives prior to the imaging study.
Albuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Alprazolam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Amantadine: (Major) Amantadine used concomitantly with psychostimulants, such as caffeine, can result in increased stimulant effects, such as nervousness, irritability, or insomnia, and can lead to seizures or cardiac arrhythmias. Close monitoring of the patient is recommended.
Amiodarone: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
Amobarbital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Amphetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Amphetamine; Dextroamphetamine Salts: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Amphetamine; Dextroamphetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Anagrelide: (Moderate) Anagrelide has been shown to inhibit CYP1A2. In theory, coadministration of anagrelide with substrates of CYP1A2, including caffeine, could lead to increases in the serum concentrations of caffeine and, thus, adverse effects.
Arformoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Armodafinil: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with psychostimulants such as armodafinil. Patients taking armodafinil may need to be cautioned to avoid excessive intake of caffeine.
Articaine; Epinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Aspirin, ASA; Caffeine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Aspirin, ASA; Dipyridamole: (Major) Methylxanthines, through antagonism of adenosine and thus pharmacologic-induced coronary vasodilation, have been associated with false-negative results during dipyridamole-thallium 201 stress testing. It is recommended that caffeine be discontinued for at least 24 hours prior to stress testing. An interaction is not expected when methylxanthines are used concomitantly with the chronic dipyridamole therapy.
Barbiturates: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Barium Sulfate: (Major) Avoid caffeine containing products for at least 48 hours before myelography and for at least 24 hours postprocedure.
Benzodiazepines: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Benzphetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Beta-agonists: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Brompheniramine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Brompheniramine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Budesonide; Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Bupivacaine; Epinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Bupropion: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Bupropion; Naltrexone: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Butabarbital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Butalbital; Acetaminophen: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Caffeine; Sodium Benzoate: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Cannabidiol: (Moderate) Coadministration of cannabidiol and caffeine-containing foods/beverages may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a substrate of CYP1A2; cannabidiol may inhibit and/or induce CYP1A2 at clinically relevant concentrations.
Capmatinib: (Moderate) Reduction or limitation of the caffeine dosage in medications or caffeine in beverages and food may be necessary during concurrent capmatinib therapy. Monitor for an increase in caffeine-related adverse reactions if coadministration with capmatinib is necessary. Caffeine is a sensitive CYP1A2 substrate and capmatinib is a weak CYP1A2 inhibitor. Coadministration with capmatinib increased caffeine exposure by 134%.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Carbinoxamine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Carbinoxamine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Cetirizine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlordiazepoxide: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Chlordiazepoxide; Amitriptyline: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Chlordiazepoxide; Clidinium: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Chlorpheniramine; Dextromethorphan: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chlorpheniramine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Chromium: (Major) Some green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with green tea. Avoid this combination. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Cimetidine: (Minor) Inhibitors of CYP1A2, such as cimetidine, may inhibit the hepatic oxidative metabolism of caffeine. In patients who complain of caffeine-related side effects caffeine dosage or intake may need to be reduced.
Ciprofloxacin: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Clonazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Clorazepate: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Clozapine: (Major) Caffeine may inhibit clozapine metabolism via CYP1A2. Clozapine clearance has been decreased by roughly 14 percent during coadministration of caffeine, and a documented increase in clozapine serum concentrations has occurred in selected patients. In addition, a single case report associates the appearance of psychiatric symptoms with caffeine ingestion in one patient taking clozapine. Until more data are available, caffeine consumption should be minimized during clozapine treatment.
Codeine; Dexchlorpheniramine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Codeine; Phenylephrine; Promethazine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Darifenacin: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Caffeine may aggravate bladder symptoms and counteract the effectiveness of darifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements (e.g., guarana), or beverages (e.g., green tea, other teas, coffee, colas).
Desloratadine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Desogestrel; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dexmethylphenidate: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Dextroamphetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Dextromethorphan; Bupropion: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Diazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Diethylpropion: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Diphenhydramine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dipyridamole: (Major) Methylxanthines, through antagonism of adenosine and thus pharmacologic-induced coronary vasodilation, have been associated with false-negative results during dipyridamole-thallium 201 stress testing. It is recommended that caffeine be discontinued for at least 24 hours prior to stress testing. An interaction is not expected when methylxanthines are used concomitantly with the chronic dipyridamole therapy.
Disulfiram: (Moderate) Disulfiram has been shown to inhibit caffeine elimination. Caffeine elimination decreased by 30 percent in those patients that were not recovering alcoholics and by 24 percent in those patients that were recovering alcoholics. During disulfiram therapy, patients may need to limit their caffeine intake if nausea, nervousness, tremor, restlessness, palpitations, or insomnia complaints occur. Adverse events were not noted during this pharmacokinetic study; however, the decrease could be significant in some patients, including some patients with cardiovascular disease.
Dobutamine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dopamine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Drospirenone; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Dyphylline: (Major) The concurrent administration of caffeine to patients taking dyphylline may produce excessive caffeine-like side effects such as nausea, irritability, or nervousness. Adverse effects such as tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently with methylxanthine drugs. Patients taking dyphylline; guaifenesin should avoid medications containing caffeine when possible. Patients may also need to limit their intake of caffeine-containing beverages or foods (e.g., coffee, green tea, other teas, guarana, colas, or chocolate) to avoid caffeine-like side effects.
Dyphylline; Guaifenesin: (Major) The concurrent administration of caffeine to patients taking dyphylline may produce excessive caffeine-like side effects such as nausea, irritability, or nervousness. Adverse effects such as tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently with methylxanthine drugs. Patients taking dyphylline; guaifenesin should avoid medications containing caffeine when possible. Patients may also need to limit their intake of caffeine-containing beverages or foods (e.g., coffee, green tea, other teas, guarana, colas, or chocolate) to avoid caffeine-like side effects.
Echinacea: (Moderate) Echinacea may inhibit the metabolism of caffeine. Monitor patients for signs of increased caffeine serum concentrations if these drugs are coadministered until more data are available.
Ephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Ephedrine; Guaifenesin: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Epinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Ergotamine; Caffeine: (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Erythromycin: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Esketamine: (Moderate) Patients who regularly consume caffeine-containing foods or beverages may need to limit caffeine intake during esketamine treatment. Blood pressure should be closely monitored in patients treated with esketamine who regularly consume caffeine. Esketamine can increase blood pressure at all recommended doses and caffeine is a stimulant that may cause additive effects on blood pressure when combined with esketamine.
Estazolam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Eszopiclone: (Moderate) In general, patients taking medications for insomnia should not use caffeine-containing products including medications, dietary supplements (e.g., guarana), and beverages (e.g., coffee, green tea, other teas, or colas) prior to going to bed as these products, theoretically, may pharmacodynamically antagonize the sedative effects of eszopiclone.
Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Ethinyl Estradiol; Norelgestromin: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Ethinyl Estradiol; Norgestrel: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ethotoin: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Etonogestrel; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Fexofenadine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Fluconazole: (Moderate) Fluconazole has been shown to inhibit the clearance of caffeine by 25 percent. The clinical significance of these interactions has not been determined.
Flurazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Fluticasone; Salmeterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Fluticasone; Vilanterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Fluvoxamine: (Moderate) Inhibitors of CYP1A2, such as fluvoxamine, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine-related side effects. In such patients, the dosage of caffeine-containing medications or the ingestion of caffeine-containing products may need to be reduced.
Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Formoterol; Mometasone: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Fosphenytoin: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Givosiran: (Major) Avoid concomitant use of givosiran and caffeine due to the risk of increased caffeine-related adverse reactions. If use is necessary, consider decreasing the caffeine dose. Caffeine is a sensitive CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glycopyrrolate; Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Grapefruit juice: (Minor) Data are limited and conflicting as to whether grapefruit juice significantly alters the serum concentrations and/or AUC of caffeine. Caffeine is primarily a CYP1A2 substrate, and grapefruit juice appears to have but a small effect on this enzyme in vivo. One report suggests that grapefruit juice decreases caffeine elimination by inhibition of flavin-containing monooxygenase, a P450 independent system. This interaction might increase caffeine levels and mildly potentiate the clinical effects and common side effects of caffeine. If side effects appear, patients may need to limit either caffeine or grapefruit juice intake.
Green Tea: (Major) Some green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with green tea. Avoid this combination. (Moderate) Certain foods that contain high amounts of caffeine or theobromine should be limited during the therapeutic use of caffeine in order to limit additive methylxanthine effects. While taking Caffeine-containing medicines, limit the use of foods, beverages (examples: coffee, tea, colas), herbs (examples: guarana, green tea) and other products that contain additional caffeine, such as chocolate and some non-prescription medications or dietary supplements for headache, insomnia, or weight loss. Too much Caffeine can cause effects like nausea, nervousness, or sleeplessness. Some drug products for adults that contain caffeine have about as much caffeine as a cup of coffee.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Guaifenesin; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Guaifenesin; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Hydantoins: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Hydrocodone; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Ibritumomab Tiuxetan: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Ibuprofen; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Indacaterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Indacaterol; Glycopyrrolate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ipratropium; Albuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Isocarboxazid: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
Isoniazid, INH: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
Isoniazid, INH; Rifampin: (Moderate) Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ketoconazole: (Minor) Ketoconazole has been shown to inhibit the clearance of caffeine by 11 percent. The clinical significance of this interaction has not been determined.
Levalbuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Levoketoconazole: (Minor) Ketoconazole has been shown to inhibit the clearance of caffeine by 11 percent. The clinical significance of this interaction has not been determined.
Levonorgestrel; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Lidocaine; Epinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Linezolid: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
Lisdexamfetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Lithium: (Major) Caffeine appears to reduce serum lithium concentrations. In 11 coffee-drinking patients stabilized on lithium, serum lithium concentrations increased during 2 weeks when coffee was withheld and fell when coffee was resumed. Lithium ADRs have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. Clinicians should note, however, that coffee, not pure caffeine, was the variable in this study. Other beverages that contain significant amounts of caffeine include green tea, other teas, and cola. Because guarana contains a substantial caffeine content, this herb should be avoided in patients taking lithium.
Loratadine; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Lorazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Metaproterenol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Methamphetamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
Methenamine; Sodium Acid Phosphate: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Methohexital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Methylphenidate Derivatives: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Methylphenidate: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Midazolam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Midodrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Modafinil: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Monoamine oxidase inhibitors: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
Naproxen; Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Caffeine and caffeine containing products should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours post-procedure.
Norepinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Norethindrone; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Norgestimate; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as caffeine. Concomitant administration of 200 mg caffeine as a single dose with obeticholic acid 10 mg once daily resulted in a 42% increase in caffeine AUC and a 6% increase in caffeine Cmax. Therapeutic monitoring is recommended with coadministration. No specific management is recommended except in patients who complain of caffeine-related side effects like nausea, tremor, or palpitations. In such patients, the dosage of caffeine-containing medications or the ingestion of caffeine-containing products may need to be reduced.
Olodaterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Oxazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Oxybutynin: (Minor) Consuming greater than 400 mg/day caffeine has been associated with the development of urinary incontinence. Caffeine may aggravate bladder symptoms and counteract the effectiveness of drugs used to treat overactive bladder such as oxybutynin.
Oxymetazoline: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Caffeine should be avoided or used cautiously with oxymetazoline.
Pentobarbital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Phendimetrazine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phenelzine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
Phenobarbital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Phentermine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phentermine; Topiramate: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phenytoin: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Potassium Phosphate; Sodium Phosphate: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Prilocaine; Epinephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Primidone: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Procarbazine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
Promethazine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Promethazine; Phenylephrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Pseudoephedrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Pseudoephedrine; Triprolidine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Quazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Racepinephrine: (Moderate) Patients who are using racepinephrine inhalation are advised to avoid foods and beverages that contain caffeine. They should also avoid dietary supplements containing ingredients, such as caffeine, that are reported or claimed to have a stimulant effect. If a patient is taking prescribed medications containing caffeine, then they should seek health care professional advice prior to the use of racepinephrine. Additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate may be additive. Consider alternatives to racepinephrine for the treatment of asthma.
Regadenoson: (Major) Regadenoson may cause an increased coronary blood flow without regard to prior caffeine ingestion. Patients should avoid consumption of any products containing caffeine (including caffeine from foods and beverages such as coffee, green tea, other teas, colas, and chocolate) for at least 12 hours before regadenoson administration.
Remimazolam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Rucaparib: (Moderate) Monitor for an increase in caffeine-related adverse reactions if coadministration with rucaparib is necessary. Some patients may need to reduce or limit their caffeine intake. Caffeine is a sensitive CYP1A2 substrate and rucaparib is a weak CYP1A2 inhibitor. Concomitant use increased the AUC of caffeine by 2.55-fold.
Salmeterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Secobarbital: (Moderate) Caffeine has been reported to increase the metabolism of barbiturates, and barbiturates increase caffeine elimination. Higher caffeine doses may be needed after barbiturate administration.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Serum concentrations of caffeine may be increased during concurrent administration with ethinyl estradiol. Patients may desire to limit products that contain high amounts of caffeine in an effort to minimize caffeine-related side effects such as nausea or tremors.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Sodium Oxybate: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Solifenacin: (Minor) Beverages containing caffeine may aggravate bladder symptoms and counteract the effectiveness of solifenacin to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
Solriamfetol: (Moderate) Patients who regularly consume caffeine-containing foods or beverages may need to limit caffeine intake during solriamfetol treatment. Blood pressure and heart rate should be closely monitored in patients treated with solriamfetol who regularly consume caffeine. Solriamfetol can increase blood pressure and heart rate; caffeine is a stimulant that may cause additive effects on blood pressure or heart rate when combined with solriamfetol.
Tacrine: (Moderate) Inhibitors of CYP1A2, such as tacrine, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine-related side effects like nausea, tremor, or palpitations. In such patients, the dosage of caffeine-containing medications or the ingestion of caffeine-containing products may need to be reduced.
Temazepam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Terbinafine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Terbutaline: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Theophylline, Aminophylline: (Major) Caffeine is a CNS stimulant. The concurrent administration of caffeine to patients taking aminophyllinemay produce excessive caffeine-like side effects, such as nausea, irritability or nervousness. Adverse effects such as tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently. Patients should avoid medications containing caffeine when possible. Patients may also need to limit their intake of caffeine-containing beverages or foods (e.g., coffee, green tea, other teas, colas, or chocolate) to avoid caffeine-like side effects. (Moderate) Caffeine is a CNS stimulant. The concurrent administration of caffeine to patients taking theophylline may produce excessive caffeine-like side effects, such as nausea, irritability or nervousness. Adverse effects such as tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently with theophylline. Patients taking theophylline should avoid medications containing caffeine when possible. Patients may also need to limit their intake of caffeine-containing beverages or foods (e.g., coffee, green tea, other teas, colas, or chocolate) to avoid caffeine-like side effects.
Tiotropium; Olodaterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Tobacco: (Major) Advise patients who are taking caffeine to avoid smoking tobacco. Smoking tobacco has been observed to increase caffeine clearance by 50% to 70%. Caffeine is a CYP1A2 substrate and smoking tobacco induces CYP1A2.
Tolterodine: (Minor) Beverages containing caffeine may aggravate bladder symptoms and counteract the effectiveness of tolterodine to some degree. Patients may wish to limit their intake of caffeinated drugs, dietary supplements, or beverages.
Trandolapril; Verapamil: (Minor) Verapamil reduces the clearance of caffeine and increases serum caffeine concentrations, presumably via inhibition of hepatic metabolism. During concomitant therapy with verapamil, it may be prudent to advise patients to limit or minimize the intake of caffeinated products to minimize caffeine-related side effects.
Tranylcypromine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
Triazolam: (Minor) Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.
Trospium: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Caffeine may aggravate bladder symptoms and counteract the effectiveness of drugs used to treat overactive bladder, like trospium, to some degree. Patients with overactive bladder may wish to limit their intake of caffeine including caffeine from drugs, dietary supplements (i.e., guarana), beverages (i.e., teas, coffee, colas), or foods (i.e., chocolate).
Umeclidinium; Vilanterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Vemurafenib: (Minor) Coadministration of vemurafenib and caffeine increased the caffeine AUC by 2.6-fold. Vemurafenib is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate. The manufacturer of vemurafenib suggests that concomitant use with agents with narrow therapeutic windows that are metabolized by CYP1A2 is not recommended. Theophylline (or aminophylline), another methylxanthine, is also primarily a CYP1A2 substrate with a narrow therapeutic index. If coadministration cannot be avoided, the manufacturer recommends considering a dose reduction of the concomitant drug; it may also be prudent to monitor for signs and symptoms of theophylline toxicity during coadministration. Some patients may need to reduce intake of caffeine from non-drug sources (e.g., beverages) during treatment to avoid caffeine-related side effects.
Verapamil: (Minor) Verapamil reduces the clearance of caffeine and increases serum caffeine concentrations, presumably via inhibition of hepatic metabolism. During concomitant therapy with verapamil, it may be prudent to advise patients to limit or minimize the intake of caffeinated products to minimize caffeine-related side effects.
Vincristine Liposomal: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
Zileuton: (Moderate) Inhibitors of CYP1A2, such as zileuton, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine-related side effects like nausea, tremor, or palpitations. In such patients, the dosage of caffeine-containing medications or the ingestion of caffeine-containing products may need to be reduced.
Zolpidem: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages within the hours close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep. However, in healthy subjects (without insomnia) in a pharmacokinetic study, coadministration of caffeine at a dosage of 150 to 300 mg with zolpidem did not counteract the sedative effects of a single 10 mg dose of zolpidem.