Ergotamine; caffeine are used in combination as an abortive treatment for migraine and cluster headaches. This medication is still considered a primary treatment option by many clinicians because of its efficacy in controlling up to 70% of migraine attacks in adults and its relative cost advantage compared to other anti-migraine medications. Prolonged use or excessive dosage of this drug combination can lead to ergotism, dependence, and/or rebound headaches. Ergotamine; caffeine should be prescribed in strict accordance with the manufacturer's guidelines. Maximum daily and weekly dosage limits should not be exceeded. A suppository formulation of the drug is available for those who cannot tolerate oral administration due to nausea/vomiting during migraine attacks. Ergotamine was first used medically to treat migraines in the 1920s, and was approved by the FDA in 1960.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Ergotamine; caffeine is more effective if taken early in the migraine attack.
-Do not to exceed maximum daily or weekly dosage limits.
Rectal Administration
-Instruct patient on the proper use of suppositories.
-Remove the wrapper. Moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over the suppository before removing the wrapper.
-Do not to exceed maximum daily or weekly dosage limits.
Nausea/vomiting are common gastrointestinal complaints in patients receiving ergotamine; caffeine. This reaction is the result of the potent emetic properties of ergotamine, which originate in the chemoreceptor trigger zone. The frequency and/or severity of this adverse reaction may be reduced by the concomitant administration of an antiemetic agent with caffeine; ergotamine combinations. Diarrhea may also be a reported side effect. Ischemic colitis (bowel ischemia) due to ergot alkaloid-induced vasospasm has been reported.
Effects related to the vasoconstrictive properties of ergotamine include ischemia, cyanosis, absence of pulse, myalgia, paresthesias, and weakness or coldness in the extremities. Peripheral vasoconstriction of the arteries may result in tissue necrosis, which may lead to gangrene. Ergotamine may also cause coronary vasospasm; patients who report chest pain (unspecified) may require evaluation. Angina and ECG changes may occur. Transient sinus tachycardia, bradycardia, and hypertension have been reported. Vasoconstrictive effects are more likely to occur with long-term use with relatively high doses; however, they have also been reported with short-term use or normal doses. Prolonged administration or excessive dosages of ergotamine; caffeine may result in ergotamine toxicity. While ergot-toxicity has occurred in patients taking less than 5 mg of ergotamine, toxicity is more likely to occur in those patients taking more than 15 mg/24 hours or 40 mg within a few days. Muscle cramps (claudication) have also occurred. Other potential serious complications include severe abdominal pain with mesenteric ischemia or artery thrombosis, myocardial infarction, and renal stenosis or renal tubular necrosis. Symptoms such as confusion, drowsiness, and seizures rarely occur, and have been noted primarily in overdose. Overuse of the suppository formulation of the drug may cause the above symptoms as well as rectal or anal ulcerations. Patients should report any of the described symptoms promptly to their prescriber and the drug should be discontinued.
The caffeine component of ergotamine; caffeine combinations is a CNS stimulant. At therapeutic or nontoxic doses, caffeine can cause heightened attentiveness, sinus tachycardia, and tremor. Caffeine is also a mild diuretic; polyuria can occur.
Vertigo has been observed with ergotamine; caffeine use.
Do not prescribe ergotamine; caffeine for use in pregnant patients. Although specific effects of ergotamine are not attributable to teratogenesis, it is known that the drug may induce fetal harm. Retarded fetal growth and an increase in intrauterine fetal death, including spontaneous fetal abortion, have been seen in animals. Ergotamine stimulates uterine contractions and is a potent vasoconstrictor of the placental vascular bed. Caffeine does cross the placenta.
Long-term use of ergot alkaloids such as ergotamine in ergotamine; caffeine has been associated with the development of cardiac valvulopathy. Such effects have included aortic and/or mitral regurgitation, mitral stenosis, severe tricuspid regurgitation, and pulmonary regurgitation. Chronic use of ergotamine preparations has caused fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves. Retroperitoneal fibrosis and pulmonary fibrosis have occurred in rare instances.
Drug dependence may occur in some individuals after prolonged use of ergotamine; caffeine. Withdrawal symptoms such as dysphoria and/or rebound headaches have been reported after abrupt discontinuation of ergotamine. Monitor patients for possible physiological dependence and/or withdrawal while receiving ergotamine; caffeine. In addition, a caffeine withdrawal syndrome has been described in patients who have consumed or received caffeine daily for several weeks. Withdrawal symptoms include notable physical and psychiatric responses such as anxiety, dizziness, headache, or lethargy. Overuse of drugs for treating acute headaches, including ergotamine; caffeine, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of ergotamine; caffeine or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use.
Hypersensitivity reactions including urticaria, pruritus, and face edema are associated with ergotamine; caffeine use.
Ergotamine; caffeine is contraindicated in patients with known ergot alkaloid hypersensitivity because they may develop an allergic or otherwise serious adverse reaction. Patients should be advised not to exceed the recommended dosage of ergotamine during use. Patients should report any of the following symptoms: abdominal pain, anxiety, chest pain, myalgia, severe nausea and vomiting, numbness, tingling, or vision changes. If signs and symptoms of impaired circulation occur, the medication should be discontinued, and affected extremities should be kept warm.
Ergotamine; caffeine use should be avoided in basilar/hemiplegic migraine because safety and efficacy have not been established. Treatment for migraine-induced stroke has not been formally evaluated and ergot alkaloids for abortive therapy of the migraine should be avoided because they may further reduce cerebral blood flow to the ischemic area. Ergotamine; caffeine is not recommended for migraine prophylaxis.
Ergotamine; caffeine is contraindicated in peripheral vascular disease (including thromboangiitis obliterans (Buerger's disease), luetic arteritis, severe arteriosclerosis, thrombophlebitis, and Raynaud's phenomenon), coronary artery disease (including unstable or vasospastic angina, or predisposition to vasospastic reactions), sepsis or uncontrolled hypertension. Ergotamine should not be given to patients with a history of myocardial infarction or in whom unrecognized coronary artery disease (CAD) is predicted by the presence of cardiac disease risk factors (e.g., hypertension, hypercholesterolemia, current tobacco smoking, obesity, diabetes mellitus, strong family history of CAD, postmenopausal females, or males over 40 years of age), unless a cardiovascular evaluation provides sufficient evidence that the patient is reasonably free of ischemic heart disease. Geriatric patients may be more susceptible to vasoconstrictive effects of ergot alkaloids, and in general, dosing should be more cautious in the elderly, starting at the lower end of the dose range to account for differences in renal, hepatic, or cardiac systems as well as concomitant disease states and medications. Coadministration of ergotamine with potent inhibitors of CYP3A4 is contraindicated due to the risk of acute ergot toxicity. Serious and/or life-threatening peripheral vasoconstriction or ischemia has been associated with the coadministration of ergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics, with some cases resulting in limb amputation. Cerebral ischemia has occurred rarely in patients taking ergotamine with protease inhibitors (one case fatal). Because CYP3A4 inhibition elevates serum ergotamine concentrations, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased.
Ergotamine is extensively metabolized in the liver and excreted in the bile. Hepatic impairment is considered a contraindication to ergotamine; caffeine use by the manufacturer. Those with hepatic disease may be at increased risk for developing ergot toxicity due to systemic accumulation of the drug. Use in severe pruritus (i.e., biliary tract disease or cholestasis) should be avoided.
Renal impairment, including renal failure, is considered a contraindication to ergotamine; caffeine use by the manufacturer. Patients with severe renal impairment who receive ergotamine may develop symptoms of ergot poisoning because of impaired elimination. Use with caution in any patient with renal disease due to the vasoconstrictive effects of the drug.
Ergotamine; caffeine should be used with caution in children, including adolescents. Safe and effective use has not been established. While older children have been treated for severe migraine headaches with ergotamine, limited clinical data reveal a poor efficacy rate. Use in older children should be reserved for cases where less toxic medications have failed to provide relief. Do not give ergotamine to young children or infants.
Ergotamine; caffeine is classified as FDA pregnancy risk category X. Ergotamine and other ergot alkaloids are contraindicated during pregnancy because the potent oxytocic and uterine stimulant properties of this drug class will likely cause harm to the fetus. Ergotamine is also contraindicated in labor and obstetric delivery due to its oxytocic effect which is maximal in the third trimester. Although ergotamine is not an established human teratogen, limited data indicate that in utero exposure to ergotamine or ergotamine-containing products during pregnancy may be associated with fetal malformations, primarily consistent with ischemic injury. Until further information becomes available, the possibility of teratogenic potential in humans cannot be ruled out, particularly during prolonged administration or use of high doses. Patients with eclampsia or preeclampsia should not receive ergot alkaloids; these conditions may be exacerbated and patients may be more likely to experience ergot-related side effects. Animal studies indicate that ergotamine inhibits fetal growth, and increases intrauterine deaths and resorption. Prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone leading to reduced myometrial and placental blood flow may contribute to the inhibition of fetal growth observed in animals. Caffeine is known to cross the placenta and has been shown to be teratogenic in animals. Women of child-bearing potential should be counseled on the potential risks to the fetus should pregnancy occur during use of caffeine; ergotamine.
Ergot derivatives should generally be avoided during breast-feeding. According to the manufacturer of ergotamine; caffeine, a decision should be made to discontinue nursing or discontinue the drug due to the potential for serious adverse reactions in the nursing infant. Ergotamine is excreted in breast milk and may cause symptoms indicative of ergot toxicity including vomiting, diarrhea, seizures, weak pulse, and unstable blood pressure in nursing infants. Ergotamine is classified by the American Academy of Pediatrics (AAP) as a drug that has been associated with significant effects on some nursing infants and should be given to nursing mothers with caution. Ergot derivatives are known to inhibit prolactin, and thus, interference with proper lactation is possible. Sumatriptan, a serotonin receptor agonist indicated for the treatment of migraines, is classified by the AAP as usually compatible with breast-feeding. Sumatriptan may be considered as an alternative to caffeine; ergotamine for the acute treatment of migraines in breast-feeding mothers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Ergotamine; caffeine preparations should be used cautiously in those with pulmonary disease or valvular heart disease. Long-term use of ergot alkaloids such as ergotamine has been associated with abnormal heart valve findings including aortic and/or mitral regurgitation, mitral stenosis, severe tricuspid regurgitation, and pulmonary regurgitation. Chronic use of ergotamine preparations has caused fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves. Retroperitoneal fibrosis and pulmonary fibrosis have occurred in rare instances.
Ergotamine may cause vasoconstriction, thus, patients should be advised to inform their health care provider of ergotamine; caffeine usage prior to any surgeries or related procedures. Ergotamine may cause problems with plastic, cosmetic, or reconstructive surgery in particular; cyanosis, ischemia and vasoconstriction in the skin or other tissues may occur if ergotamine has been ingested within 48 hours of the surgical procedure.
For the acute treatment of migraine:
Oral dosage (tablets containing 1 mg of ergotamine and 100 mg of caffeine):
Adults: 2 mg ergotamine/100 mg caffeine PO at the start of attack, followed by 1 mg ergotamine/100 mg caffeine PO every 30 minutes if needed for full relief. Max: 6 mg/attack ergotamine/600 mg/attack caffeine and 10 mg/week ergotamine/1,000 mg/week caffeine. Guidelines classify oral caffeine; ergotamine as having probable efficacy for the treatment of acute migraine.
Rectal dosage (suppositories containing 2 mg of ergotamine and 100 mg of caffeine):
Adults: 2 mg ergotamine/100 mg caffeine PR at the start of attack, followed by 2 mg ergotamine/100 mg caffeine PR 1 hour later if needed for full relief. Max: 4 mg/attack ergotamine/200 mg/attack caffeine and 10 mg/week ergotamine/500 mg/week caffeine.
Maximum Dosage Limits:
-Adults
6 tablets/24 hours or per attack PO and not to exceed 10 tablets/week PO; or 2 suppositories/24 hours or per attack PR and not to exceed 5 suppositories/week PR.
-Elderly
6 tablets/24 hours or per attack PO and not to exceed 10 tablets/week PO; or 2 suppositories/24 hours or per attack PR and not to exceed 5 suppositories/week PR.
-Adolescents
Safety and efficacy have not been established.
-Children
>= 10 years: Safety and efficacy have not been established.
< 10 years: Not recommended.
Patients with Hepatic Impairment Dosing
Use contraindicated. Those with hepatic disease may be at increased risk for developing ergot toxicity due to systemic accumulation of ergotamine.
Patients with Renal Impairment Dosing
Use contraindicated. Patients with severe renal impairment may develop symptoms of ergot toxicity because of impaired ergot elimination.
Intermittent hemodialysis
Contraindicated to use ergotamine; caffeine in patients on intermittent hemodialysis therapy. However, ergotamine is hemodialyzable.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Aspirin: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Dextromethorphan; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Acetaminophen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Aclidinium; Formoterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acrivastine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Acyclovir: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Adagrasib: (Contraindicated) Concomitant use of ergotamine with adagrasib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
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 consumption of methylxanthine-containing products, including caffeinated beverages, for at least 5 half-lives prior to the imaging study.
Albuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Albuterol; Budesonide: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Allopurinol: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of allopurinol is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and allopurinol is a CYP1A2 inhibitor.
Almotriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor 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: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of amiodarone is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and amiodarone is a CYP1A2 inhibitor. (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and amiodarone. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and amiodarone is a moderate CYP3A inhibitor.
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.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Amphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (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 Salts: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (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: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (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.
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.
Angiotensin II: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and aprepitant/fosaprepitant. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor.
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 armodafinil. Caffeine should be used cautiously with armodafinil. Intake of caffeine should be limited. Excessive intake may cause nervousness, irritability, insomnia, or other side effects.
Articaine; Epinephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Aspirin, ASA: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
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. (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
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 methylxanthines (caffeine, caffeinated beverages and foods, theophylline, etc.) be discontinued for at least 24 hours prior to stress testing. An interaction is not expected when methylxanthines are used concomitantly with chronic dipyridamole therapy. (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Omeprazole: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Oxycodone: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Atazanavir: (Contraindicated) Concomitant use of ergotamine with atazanavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of ergotamine with atazanavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
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.
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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and methylene blue. Both medications enhance serotonergic activity.
Benzphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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.
Berotralstat: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and berotralstat. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Beta-agonists: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Bromocriptine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Brompheniramine; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Brompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (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.
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.
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.
Butalbital; Aspirin; 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. (Minor) Caffeine has been reported to increase the metabolism of aspirin.
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.
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) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Capmatinib: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of capmatinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and capmatinib is a CYP1A2 inhibitor. Coadministration with capmatinib increased caffeine exposure by 134%.
Carbamazepine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Ceritinib: (Contraindicated) Concomitant use of ergotamine with ceritinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Cetirizine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Chloramphenicol: (Contraindicated) Concomitant use of ergotamine with chloramphenicol is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
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; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Chlorpheniramine; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Chlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and ciprofloxacin. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. (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.
Citalopram: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and citalopram. Both medications enhance serotonergic activity.
Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
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.
Cobicistat: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Cocaine: (Contraindicated) Concomitant use of ergotamine with cocaine is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Conivaptan: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and conivaptan. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and crizotinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and cyclosporine. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cyclosporine is a moderate CYP3A inhibitor.
Danazol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and danazol. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Darifenacin: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Caffeine may aggravate bladder symptoms, increase urination, 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).
Darunavir: (Contraindicated) Concomitant use of ergotamine with darunavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Contraindicated) Concomitant use of ergotamine with darunavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Contraindicated) Concomitant use of ergotamine with darunavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Delavirdine: (Contraindicated) Concomitant use of ergotamine with delavirdine is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Desloratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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 to minimize caffeine-related side effects such as nausea or tremors.
Desvenlafaxine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
Dexbrompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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 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.
Dextroamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (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.
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: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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; Guaifenesin; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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.
Diltiazem: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and diltiazem. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor.
Diphenhydramine; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
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 methylxanthines (caffeine, caffeinated beverages and foods, theophylline, etc.) be discontinued for at least 24 hours prior to stress testing. An interaction is not expected when methylxanthines are used concomitantly with 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 in caffeine clearance could be significant in some patients, including some patients with cardiovascular disease.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Dopamine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Doxapram: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants, like doxapram. CNS stimulants and sympathomimetics are associated with adverse effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias, and the concomitant use of these drugs increases the risk of developing such adverse reactions. Coadminsitration should be avoided or used cautiously.
Dronedarone: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and dronedarone. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
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 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 to minimize caffeine-related side effects such as nausea or tremors.
Droxidopa: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Duloxetine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
Duvelisib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and duvelisib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Echinacea: (Moderate) Echinacea may inhibit the metabolism of caffeine. Echinacea reduces the oral clearance of caffeine by 27 percent and increases the mean AUC by 129 percent. Monitor patients for signs of increased caffeine serum concentrations if these drugs are coadministered until more data are available.
Eletriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Enasidenib: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of enasidenib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and enasidenib is a CYP1A2 inhibitor.
Ephedrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants like ephedrine. Adverse effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently with ephedrine. 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.
Ephedrine; Guaifenesin: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants like ephedrine. Adverse effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias are also possible when excessive dosages of caffeine are taken concurrently with ephedrine. 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.
Epinephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
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. (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and erythromycin. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Escitalopram: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and escitalopram. Both medications enhance serotonergic activity.
Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and caffeine. Coadministration of psychostimulants, such as caffeine, with esketamine may increase blood pressure.
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: (Minor) Patients taking eszopiclone for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime, as well as excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep. Limit use of caffeine-containing products including medications, dietary supplements (e.g., guarana), and beverages (e.g., coffee, green tea, other teas, or colas).
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 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 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 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 post-procedure.
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 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 to minimize caffeine-related side effects such as nausea or tremors.
Fedratinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and fedratinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Fesoterodine: (Minor) Beverages containing caffeine or ethanol may aggravate bladder symptoms and counteract the effectiveness of fesoterodine 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) and alcoholic beverages.
Fexinidazole: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of fexinidazole is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and fexinidazole is a CYP1A2 inhibitor.
Fexofenadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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. (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and fluconazole. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Fluoxetine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and fluoxetine. Both medications enhance serotonergic activity.
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) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, serotonin syndrome, and symptoms of serotonin excess, such as weakness, hyperreflexia, and incoordination, during concomitant use of ergotamine and fluvoxamine. Concomitant use may increase ergotamine exposure and both medications enhance serotonergic activity. Ergotamine is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor. (Moderate) Strong inhibitors of CYP1A2, such as fluvoxamine, may inhibit the metabolism of caffeine. No specific management is recommended except in patients with caffeine-related side effects after initiating fluvoxamine. 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.
Fosamprenavir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and fosamprenavir. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Frovatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
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: (Major) The risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects) from ergotamine is potentially increased by the use of CYP3A4 inhibitors. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level. Therefore grapefruit juice may decrease ergotamine metabolism via CYP3A4. According to the manufacturers, the prescriber should consider the effects of other agents on CYP3A4 before concomitant use with ergotamine. (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: (Moderate) Many green tea products contain caffeine. Due to the risk for adverse effects, avoid the concurrent administration of caffeine and green tea products that contain caffeine when possible. Concurrent administration can produce excessive caffeine-related adverse events such as nausea, irritability, nervousness, and insomnia. (Minor) Advise patients to consider avoiding excess caffeine intake via dietary supplements while taking ergotamine. The net effect of excess caffeine intake on ergotamine efficacy and adverse effects is unclear and likely to vary based on the amount of caffeine ingested and timing of consumption. Oral caffeine has been observed to increase the rate and extent of absorption of oral ergotamine which may increase overall ergotamine exposure. Additionally, caffeine is a cranial vasoconstrictor. Concomitant use may improve ergotamine efficacy or cause a synergistic increase in blood pressure and increase the risk for vasospastic adverse effects including cerebral or peripheral ischemia.
Guaifenesin; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Hydantoins: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Hydralazine; Isosorbide Dinitrate, ISDN: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Hydrocodone; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and methylene blue. Both medications enhance serotonergic activity.
Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Idelalisib: (Contraindicated) Concomitant use of ergotamine with idelalisib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Imatinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and imatinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Indacaterol; Glycopyrrolate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Indinavir: (Contraindicated) Concomitant use of ergotamine with indinavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and indinavir is a strong CYP3A inhibitor.
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 post-procedure.
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 post-procedure.
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 post-procedure.
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 post-procedure.
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 post-procedure.
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 post-procedure.
Ipratropium; Albuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Isavuconazonium: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and isavuconazonium. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor.
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. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
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. (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
Isoproterenol: (Contraindicated) Concomitant use of ergotamine with isoproterenol is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Isosorbide Dinitrate, ISDN: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Isosorbide Mononitrate: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
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 post-procedure.
Itraconazole: (Contraindicated) Concomitant use of ergotamine with itraconazole is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor.
Ketoconazole: (Contraindicated) Concomitant use of ergotamine with ketoconazole is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. (Moderate) Ketoconazole has been shown to inhibit the clearance of caffeine by 11 percent. The clinical significance of these interactions has not been determined.
Ketoprofen: (Minor) Caffeine administered concurrently with ketoprofen reduced the urine volume in 4 healthy volunteers. The clinical significance of the interaction in preterm neonates is not known.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Lefamulin: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and lefamulin. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and lefamulin is a moderate CYP3A inhibitor.
Lenacapavir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and lenacapavir. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Leniolisib: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Letermovir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and letermovir. Concomitant use of ergotamine with combination letermovir plus cyclosporine is contraindicated. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor; combination letermovir plus cyclosporine acts as a strong CYP3A inhibitor.
Levalbuterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Levoketoconazole: (Contraindicated) Concomitant use of ergotamine with ketoconazole is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. (Moderate) Ketoconazole has been shown to inhibit the clearance of caffeine by 11 percent. The clinical significance of these interactions has not been determined.
Levomilnacipran: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
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 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 to minimize caffeine-related side effects such as nausea or tremors.
Levonorgestrel; 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 to minimize caffeine-related side effects such as nausea or tremors.
Lidocaine; Epinephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Linezolid: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and linezolid. Both medications enhance serotonergic activity.
Lisdexamfetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Moderate) Avoid excessive caffeine intake during use of lisdexamfetamine. 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.
Lithium: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Lonafarnib: (Contraindicated) Concomitant use of ergotamine with lonafarnib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of ergotamine with ritonavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Loratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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.
Melatonin: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime, as well as excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Mepivacaine: (Major) If epinephrine is added to mepivacaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
Metaproterenol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Methamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (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 methamphetamine. 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.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and methylene blue. Both medications enhance serotonergic activity.
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.
Methylene Blue: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and methylene blue. Both medications enhance serotonergic activity.
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 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.
Mexiletine: (Moderate) Mexiletine is an inhibitor of CYP1A2 isoenzymes, and may reduce CYP1A2-mediated caffeine metabolism. Mexiletine has been shown to increase caffeine concentrations by as much as 23 percent after a single 200 mg dose of mexiletine (nonsignificant increase, p<0.1). Another study has reported that the elimination of caffeine is decreased by 50 percent. While the clinical significance of this interaction is not known, elevated plasma caffeine levels may be of concern in patients with arrhythmias. Patients with cardiac arrhythmias on mexiletine should be cautioned to limit their intake 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: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Mifepristone: (Contraindicated) Concomitant use of ergotamine with mifepristone is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Migalastat: (Moderate) Separate the administration of oral caffeine and migalastat by at least 2 hours if concomitant use is necessary. Simultaneous coadministration may decrease migalastat exposure and efficacy. Coadministration of 190 mg caffeine reduced the mean migalastat AUC by 55%.
Milnacipran: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
Mirtazapine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and mirtazapine. Both medications enhance serotonergic activity.
Modafinil: (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 used cautiously with modafinil. Excessive intake should be limited. Excessive intake may cause nervousness, irritability, insomnia or other side effects.
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: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Naratriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Nefazodone: (Contraindicated) Concomitant use of ergotamine with nefazodone is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Contraindicated) Concomitant use of ergotamine with nelfinavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and netupitant. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nicotine: (Major) Advise patients to avoid nicotine while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction.
Nilotinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and nilotinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ergotamine with ritonavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and ergot alkaloids is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase ergot alkaloids' exposure resulting in increased toxicity. Ergot alkaloids are CYP3A substrates and nirmatrelvir is a CYP3A inhibitor.
Nirogacestat: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and nirogacestat. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Nitrates: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Nitroglycerin: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
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: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (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 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 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 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 to minimize caffeine-related side effects such as nausea or tremors.
Obeticholic Acid: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of obeticholic acid is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 42%; caffeine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor.
Olanzapine; Fluoxetine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and fluoxetine. Both medications enhance serotonergic activity.
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, increase urine output, and counteract the effectiveness of drugs used to treat overactive bladder such as oxybutynin. 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).
Pacritinib: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of pacritinib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and pacritinib is a CYP1A2 inhibitor.
Paroxetine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and paroxetine. Both medications enhance serotonergic activity.
Peginterferon Alfa-2b: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
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: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phentermine; Topiramate: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Phenytoin: (Moderate) Higher caffeine doses may be needed after hydantoin administration; hydantoins increase caffeine elimination.
Posaconazole: (Contraindicated) Concomitant use of ergotamine with posaconazole is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Prilocaine; Epinephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (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; Phenylephrine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. 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.
Propranolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and propranolol. Propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating properties of epinephrine.
Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
Pseudoephedrine; Triprolidine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously. 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.
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.
Ramelteon: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages 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.
Ranolazine: (Major) In vitro studies indicate that ranolazine and its metabolite are inhibitors of CYP3A isoenzymes. The impact of coadministering ranolazine with other CYP3A4 substrates has not been studied. Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates, such as ergot alkaloids, potentially leading to adverse reactions.
Rasagiline: (Moderate) Although sympathomimetics and psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses.
Regadenoson: (Major) Caffeine is a non-specific adenosine receptor antagonist and can interfere with the efficacy of regadenoson. 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.
Ribociclib: (Contraindicated) Concomitant use of ergotamine with ribociclib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Contraindicated) Concomitant use of ergotamine with ribociclib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifampin: (Minor) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of caffeine, including caffeine found in green tea products.
Ritlecitinib: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of ritlecitinib is necessary; lower caffeine doses may be necessary. Concomitant use has been observed to increase caffeine overall exposure by 2.65-fold; caffeine is a CYP1A2 substrate and ritlecitinib is a CYP1A2 inhibitor. (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and ritlecitinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Contraindicated) Concomitant use of ergotamine with ritonavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Rizatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
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 2.6-fold.
Salmeterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Saquinavir: (Contraindicated) Concomitant use of ergotamine with saquinavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor.
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 to minimize caffeine-related side effects such as nausea or tremors.
Selegiline: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
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 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.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
Serotonin-Receptor Agonists: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sertraline: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and sertraline. Both medications enhance serotonergic activity.
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.
Solifenacin: (Minor) Consuming > 400 mg/day caffeine has been associated with the development of urinary incontinence. Beverages containing caffeine may aggravate bladder symptoms, increase urine output, 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) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and caffeine. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
St. John's Wort, Hypericum perforatum: (Moderate) Inducers of CYP1A2, such as St. John's wort, Hypericum perforatum, may induce the hepatic oxidative metabolism of caffeine.
Stiripentol: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Sumatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sumatriptan; Naproxen: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Suvorexant: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages 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.
Tasimelteon: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages 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.
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.
Teriflunomide: (Minor) Monitor for decreased efficacy of caffeine during coadministration of teriflunomide. Teriflunomide may be a weak inducer of CYP1A2. When teriflunomide was given concurrently with caffeine in vivo, a CYP1A2 substrate, the Cmax and AUC of caffeine decreased by 18% and 55%, respectively.
Theophylline, Aminophylline: (Major) Caffeine is a CNS stimulant. The concurrent administration of caffeine to patients taking aminophylline 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. 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. (Major) 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. In neonates, theophylline is metabolized to caffeine; initiating caffeine after theophylline therapy is halted may result in caffeine toxicity in neonates if serum caffeine levels are not monitored prior to the initiation of caffeine therapy. Concurrent use of theophylline with caffeine in neonates is not recommended due to the potential for additive toxicity.
Tiotropium; Olodaterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Tipranavir: (Contraindicated) Concomitant use of ergotamine with tipranavir is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction. Nicotine acts indirectly as a sympathomimetic agent by releasing catecholamines, potentially resulting in effects such as hypertension, coronary spasm, coronary ischemia, or cardiac arrhythmias, which may be additive with ergot alkaloids. (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: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and verapamil. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. (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.
Tucatinib: (Contraindicated) Concomitant use of ergotamine with tucatinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor.
Umeclidinium; Vilanterol: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Vasopressin, ADH: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Vasopressors: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Venlafaxine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and serotonin norepinephrine reuptake inhibitors. Both medications enhance serotonergic activity.
Verapamil: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and verapamil. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. (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.
Vilazodone: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and vilazodone. Both medications enhance serotonergic activity.
Viloxazine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of viloxazine is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and viloxazine is a CYP1A2 inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Voriconazole: (Contraindicated) Concomitant use of ergotamine with voriconazole is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor.
Vortioxetine: (Moderate) Monitor for serotonin syndrome and symptoms of serotonin excess such as weakness, hyperreflexia, and incoordination during concomitant use of ergotamine and vortioxetine. Both medications enhance serotonergic activity.
Voxelotor: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of ergotamine and voxelotor. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zaleplon: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as zaleplon should avoid caffeine-containing medications, dietary supplements, foods, and beverages 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.
Zileuton: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of zileuton is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and zileuton is a CYP1A2 inhibitor.
Zolmitriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
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.
Ergotamine; caffeine act synergistically to relieve migraine headaches. At therapeutic doses, ergotamine inhibits the uptake of norepinephrine and stimulates alpha-adrenergic receptors, causing prolonged vasoconstriction and decreased blood flow to the extremities. Inhibition of alpha-adrenergic receptors may occur with higher doses. In the treatment of migraine headache, some pharmacologic actions of ergotamine are probably related to the drugs effect on serotonin (5-HT) receptors. Ergotamine reduces extracranial blood flow, decreasing the pulsations in the cranial arteries, and decreasing hyperperfusion of the basilar artery territory. Ergotamine also exhibits potent uterine stimulant and emetic properties. Caffeine may have additive cerebral vasoconstriction activity to ergotamine, but many studies show that the increased effect from the combination is due to the enhanced GI absorption of ergotamine tartrate.
Ergotamine; caffeine combinations are administered by the oral or rectal routes.
-Ergotamine: Ergotamine is extensively metabolized in the liver by undefined pathways. About 90% of the metabolites are eliminated in the bile. Unchanged ergotamine is secreted erratically in the saliva; trace amounts appear in the feces and urine. The elimination half-life of ergotamine is roughly 2 hours; however, the drug may be stored in some tissues, which would account for its long-lasting therapeutic and toxic effects.
-Caffeine: Caffeine is distributed rapidly to all body tissues and readily crosses the blood-brain and placental barriers. It is distributed into breast milk. In adults, caffeine is partially metabolized in the liver via demethylation reactions dependent on the hepatic CYP1A2 isoenzyme; major metabolites include paraxanthine (80%), theobromine (10%) and theophylline (4%). The plasma half-life is 3 to 7 hours in adults. Metabolites are excreted in the urine.
-Route-Specific Pharmacokinetics
Oral Route
-Ergotamine: The absorption of ergotamine as a single agent is incomplete and erratic. Administration with caffeine increases the absorption rate and peak plasma levels of the drug.Peak plasma levels are achieved in about 2 hours following oral administration. The onset of action varies, and is likely related to how quickly the drug is administered once the headache begins. Typically, however, relief is obtained within 1 to 2 hours of administration.
-Caffeine: Caffeine is well absorbed by the oral route. Following administration, peak plasma concentrations in occur in roughly 1 hour.
Other Route(s)
Rectal Route
-Ergotamine: The absorption of ergotamine as a single agent is incomplete and erratic. Administration with caffeine increases the absorption rate and peak plasma levels of the drug. The rectal formulation has 20 times the bioavailability of the oral formulation. The onset of action varies, and is likely related to how quickly the drug is administered once the headache begins. Typically, however, relief is obtained within 1 to 2 hours of administration.
-Caffeine: The systemic absorption from rectal suppositories may be slower compared to the oral route.
-Special Populations
Hepatic Impairment
Use of caffeine; ergotamine is contraindicated in patients with hepatic impairment.
Renal Impairment
Use of caffeine; ergotamine is contraindicated in patients with renal impairment. Ergotamine is dialyzable.
Pediatrics
Limited controlled data exist regarding the use of caffeine; ergotamine in the pediatric population.