Ergotamine is an ergot alkaloid administered to relieve migraine headaches; the drug is roughly 70% effective in controlling acute migraine attacks. Ergotamine is more effective if taken early in the course of the migraine. Prolonged use or excessive dosage of ergot alkaloids can lead to ergotism, dependence, and/or rebound headaches. Ergotamine should be prescribed in strict accordance with manufacturer guidelines. Maximum daily and weekly dosage limits should not be exceeded. Ergotamine was first used medically to treat migraine in the 1920's, and was approved by the FDA in 1960. An inhalational form, Medihaler Ergotamine(TM), was available before 1992 from 3M Pharmaceuticals and is no longer marketed in the US. Injectable formulations are only available outside of the US.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations:
NOTE: Ergotamine is more effective if taken early in the migraine attack.
-Place tablet under the tongue and allow to dissolve; do not chew.
-Instruct patient not to swallow saliva until the tablet is completely absorbed.
-Do not to exceed maximum daily or weekly dosage limits.
Nausea and vomiting are common gastrointestinal complaints in patients receiving usual doses of ergotamine. 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 ergotamine. Other gastrointestinal side effects of ergotamine may include diarrhea. 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 (numbness and tingling), and weakness or coldness in the extremities. Peripheral vasoconstriction of the arteries may result in tissue necrosis, which may lead to gangrene. Ergotamine can also cause coronary vasospasm, and chest pain (unspecified) occurring during treatment may require evaluation. Angina and EKG changes may occur. Transient sinus tachycardia or 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 or normal doses. Prolonged administration or excessive dosages 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 been noted. 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 usually only with overdosage. Patients should report any of the described symptoms promptly to their prescriber and the drug should be discontinued.
Drug dependence may occur in some individuals after prolonged use of ergotamine. Withdrawal symptoms such as dysphoria and/or rebound headaches have been reported after abrupt discontinuation of the drug. Monitor patients for possible physiological dependence and/or withdrawal while receiving ergotamine. Overuse of drugs for treating acute headaches, including ergotamine, 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 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.
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.
Long-term use of ergot alkaloids such as ergotamine 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.
Vertigo has been observed with ergotamine use.
Hypersensitivity reactions including urticaria, pruritus, and face edema are associated with ergotamine use.
Ergotamine is contraindicated in patients with known ergot alkaloid hypersensitivity because they may develop an allergic or otherwise 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 should be avoided in patients with 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 should not be used for migraine prophylaxis.
Ergotamine is contraindicated in patients with 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, malnutrition, or uncontrolled hypertension. It is recommended that ergotamine 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. 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. The manufacturer considers hepatic impairment contraindication to ergotamine use. Those with hepatic disease may be at increased risk for developing ergot toxicity due to systemic accumulation of the drug. Use in severe pruritis (i.e., biliary tract disease or cholestasis) should be avoided.
Renal impairment, including renal failure, is considered a contraindication to ergotamine 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 should be used with caution in children, including adolescents; safe and effective use has not been established. Older children (>= 10 years) have been treated for severe migraine headaches with ergotamine. However, clinical data reveal poor efficacy rates. Ergotamine use in older children has been recommended to be reserved for cases where less toxic medications have failed to provide relief. Do not give ergotamine to young children or infants.
Ergotamine is contraindicated during pregnancy because of potent oxytocic and uterine stimulant properties that may cause fetal harm. 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. 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.
Ergot derivatives should generally be avoided during breast-feeding. According to the manufacturer of a combination product containing ergotamine, 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 the nursing infant. 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 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.
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 preparations should be used cautiously in those with pulmonary disease or valvular heart disease.
Because ergotamine may cause vasoconstriction, patients should be advised to inform their health care provider of ergotamine usage prior to any surgeries or related procedures. Ergotamine may cause problems with plastic, cosmetic, or reconstructive surgery in particular; cyanosis, ischemia, or 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:
Sublingual dosage:
Adults: 2 mg SL at the start of attack, followed by 2 mg SL every 30 minutes if needed for full relief. Max: 6 mg/day and 10 mg/week. Guidelines classify ergotamine as having possible efficacy for the treatment of acute migraine.
Maximum Dosage Limits:
-Adults
6 mg/24 hours or per attack SL; not to exceed 10 mg/week SL.
-Elderly
6 mg/24 hours or per attack SL; not to exceed 10 mg/week SL.
-Adolescents
3 mg/24 hours or per attack SL. The weekly dose limit for ergotamine is expected to be lower than for adults.
-Children
>= 10 years: 3 mg/24 hours or per attack SL. The pediatric weekly dose limit for ergotamine is expected to be lower than for adults.
< 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:
Contraindication to use. However, ergotamine is hemodialyzable.
*non-FDA-approved indication
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Amiodarone: (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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension.
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.
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.
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.
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.
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.
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.
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.
Erythromycin: (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.
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.
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.
Fluconazole: (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.
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.
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.
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.
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.
Green Tea: (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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Linezolid: (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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ritlecitinib: (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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The pharmacologic properties of ergotamine are complex; some of the pharmacologic actions are unrelated to each other; some actions are even mutually antagonistic. Ergotamine exhibits partial agonist and/or antagonist activity against serotonergic, dopaminergic, and alpha-adrenergic receptors depending on their site. Ergotamine also exhibits potent uterine stimulant and emetic properties. In the treatment of migraine headache, some pharmacologic actions are probably related to the drug's effect on serotonin (5-HT) receptors. Ergotamine reduces extracranial blood flow, decreases the amplitude of pulsations in the cranial arteries and decreases hyperperfusion of the basilar artery territory. Caffeine acts synergistically with ergotamine to treat migraine headaches (see Caffeine; Ergotamine monograph). Caffeine may have additive cerebral vasoconstriction activity to ergotamine, but some studies show the increased effect from the combination is due to the enhanced GI absorption of ergotamine tartrate.
At therapeutic doses, ergotamine inhibits the uptake of norepinephrine and stimulates alpha-adrenergic receptors, causing prolonged vasoconstriction of both arteries and veins and decreased blood flow to the extremities. Inhibition of peripheral alpha-adrenergic receptors may occur with higher doses. In doses used to treat vascular headaches, ergotamine usually only produces small elevations in blood pressure but it does increase peripheral vascular resistance and causes a decrease in blood flow to various organs. Vasoconstrictor properties may last for up to 48 hours after a single dose.
Ergotamine increases the force and frequency of uterine contraction; larger doses increase the resting uterine tone. Constriction of the placental vascular bed also occurs.
Ergotamine is administered sublingually. It is extensively metabolized in the liver, primarily via CYP3A4 isoenzymes. 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 is roughly 2 hours; however, the drug may be stored in some tissues, which would account for the long-lasting therapeutic and toxic effects of the drug.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
-Route-Specific Pharmacokinetics
Oral Route
The oral absorption of ergotamine is incomplete and erratic; bioavailability data for sublingual administration are not available. Administration with caffeine increases the absorption rate and peak plasma concentrations of ergotamine when administered orally or rectally. The onset of action varies and is likely related to how quickly the drug is administered once the headache begins. Typically, however, migraine relief is obtained within 0.5-2 hours of administration. Pharmacodynamically, the duration of other properties, like vasoconstriction, may persist for up to 48 hours.
-Special Populations
Hepatic Impairment
The manufacturers consider hepatic impairment a contraindication to ergotamine use.
Renal Impairment
The manufacturers consider renal impairment a contraindication to ergotamine use. Ergotamine is dialyzable.
Pediatrics
Limited controlled data exist on the use of ergotamine in the pediatric population.