Ergomar

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Ergomar

Classes

Ergot Alkaloids

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.

Adverse Reactions
Severe

bowel ischemia / Delayed / Incidence not known
cyanosis / Early / Incidence not known
bradycardia / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known
coronary vasospasm / Early / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
fetal death / Delayed / Incidence not known
spontaneous fetal abortion / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
cardiac valvulopathy / Delayed / Incidence not known
retroperitoneal fibrosis / Delayed / Incidence not known

Moderate

colitis / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
hypertension / Early / Incidence not known
angina / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
medication overuse headache / Delayed / Incidence not known
withdrawal / Early / Incidence not known
physiological dependence / Delayed / Incidence not known
uterine contractions / Early / Incidence not known
edema / Delayed / Incidence not known

Mild

vomiting / Early / Incidence not known
diarrhea / Early / Incidence not known
nausea / Early / Incidence not known
myalgia / Early / Incidence not known
abdominal pain / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
weakness / Early / Incidence not known
vertigo / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known

Boxed Warning
Angina, arteriosclerosis, cardiac disease, coronary artery disease, diabetes mellitus, geriatric, hypercholesterolemia, hypertension, malnutrition, myocardial infarction, obesity, peripheral vascular disease, peripheral vasoconstriction or ischemia, Raynaud's phenomenon, sepsis, thromboangiitis obliterans (Buerger's disease), thrombophlebitis, tobacco smoking

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.

Common Brand Names

Ergomar

Dea Class

Rx

Description

Ergot alkaloid; roughly 70% effective for relief of migraine. Prolonged use/excessive dose can lead to ergotism, dependence, or rebound HA; do not exceed daily and weekly dose limits.

Dosage And Indications
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.

Dosing Considerations
Hepatic Impairment

Use contraindicated. Those with hepatic disease may be at increased risk for developing ergot toxicity due to systemic accumulation of ergotamine.

Renal Impairment

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.

Drug Interactions

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; 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; 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; 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) Coadministration of ergot alkaloids and adagrasib is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates 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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of amiodarone is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates 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; 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.
Aprepitant, Fosaprepitant: (Major) Use caution if ergot alkaloids and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ergot alkaloid-related adverse effects (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects) for several days after administration of a multi-day aprepitant regimen. Ergot alkaloids are CYP3A4 substrates. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ergot alkaloids. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir; 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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
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; 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.
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.
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; 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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of ciprofloxacin is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and ciprofloxacin is a moderate CYP3A inhibitor.
Citalopram: (Moderate) Use citalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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.
Conivaptan: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of conivaptan is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates 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.
Danazol: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
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.
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.
Delavirdine: (Contraindicated) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
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) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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.
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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of diltiazem is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and diltiazem is a moderate CYP3A inhibitor.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension.
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.
Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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.
Erythromycin: (Contraindicated) Coadministration of ergot alkaloids and erythromycin is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and erythromycin is a CYP3A inhibitor.
Escitalopram: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
Fluoxetine: (Moderate) Use fluoxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Fluvoxamine: (Moderate) Use fluvoxamine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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; 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.
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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
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: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
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.
Itraconazole: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as itraconazole, or administration for 2 weeks after discontinuation of itraconazole treatment is contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Ketoconazole: (Contraindicated) Coadministration of ergot alkaloids and ketoconazole is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates 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: (Major) Avoid concomitant use of ergot alkaloids and lenacapavir and consider alternative therapy. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities.
Letermovir: (Contraindicated) Concurrent administration of ergot alkaloids and letermovir is contraindicated due to the risk of ergotism. Taking these drugs together may result in increased concentrations of ergot alkaloids due to inhibition of CYP3A4 by letermovir.
Levoketoconazole: (Contraindicated) Coadministration of ergot alkaloids and ketoconazole is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and ketoconazole is a strong CYP3A inhibitor.
Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Linezolid: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
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.
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) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Mifepristone: (Contraindicated) Coadministration of ergot alkaloids and mifepristone is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and mifepristone is a strong CYP3A inhibitor.
Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Mirtazapine: (Moderate) The use of ergot alkaloids with mirtazapine might increase the risk for serotonin syndrome. Patients receiving ergot alkaloids with mirtazapine should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, discontinue serotonergic agents and institute appropriate medical treatment.
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.
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) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and ergot alkaloids (e.g., ergotamine, dihydroergotamine), CYP3A4 substrates with a narrow therapeutic range, may result in increased ergot alkaloid levels. Avoid co-use when possible; consider alternative therapy to the ergot medication. Be alert for symptoms of ergot toxicity if these drugs together is medically necessary. An ergot alkaloid dose reduction may be necessary if these drugs are used together.
Nirmatrelvir; Ritonavir: (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.
Nitrates: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, 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.
Olanzapine; Fluoxetine: (Moderate) Use fluoxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Paroxetine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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.
Posaconazole: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
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.
Propranolol; Hydrochlorothiazide, HCTZ: (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.
Protease inhibitors: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of ritlecitinib is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and ritlecitinib is a moderate 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.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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) Use sertraline and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
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.
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 ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of verapamil is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates 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.
Vasopressors: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
Venlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Verapamil: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of verapamil is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and verapamil is a moderate CYP3A inhibitor.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as ergot alkaloids (e.g., ergotamine or dihydroergotamine). Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and an ergot alkaloid should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and the ergot alkaloid should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
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) Concurrent administration of voriconazole with ergot alkaloids is contraindicated. Voriconazole may reduce the metabolism of the ergot alkaloids via inhibition of the hepatic CYP3A4 isoenzyme, potentially increasing the risk of ergotism (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia, or other serious effects).
Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as ergot alkaloids (e.g., ergotamine or dihydroergotamine). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
Voxelotor: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of voxelotor is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates 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.

How Supplied

Ergomar Sublingual Tablet, SL: 2mg

Maximum Dosage
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.

Mechanism Of Action

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.

Pharmacokinetics

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

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.

Pregnancy And Lactation
Pregnancy

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.