Dihydroergotamine is a parenteral and nasally administered ergotamine derivative indicated for the treatment of acute migraine with or without aura and cluster headache. Dihydroergotamine is not indicated for the treatment of hemiplegic or basilar migraine or for migraine prophylaxis. Guidelines classify intranasal and parenteral dihydroergotamine as having established and probable efficacy, respectively, for the treatment of acute migraine. Serious adverse cardiac and cerebrovascular events, including acute myocardial infarction, ventricular tachycardia and ventricular fibrillation, coronary artery vasospasm, transient myocardial ischemia, cerebral hemorrhage, subarachnoid hemorrhage, and stroke, have occurred after the use of dihydroergotamine; some of these events have been fatal. Prior to initiation of dihydroergotamine, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH (Draft) 2020 List: Table 2
-Approved by FDA after NIOSH 2016 list published.
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Administer IV hydration and premedication with an antiemetic prior to administration.
-Administer via slow IV push; in pediatric patients, give dose over 3 minutes.
Inhalation Administration
Intranasal Inhalation Administration
Nasal spray assembly
-Each vial contains 1 complete dose.
-Assemble the nasal spray applicator immediately prior to use.
-Storage: Use within 8 hours after the vial is opened or the product has been assembled.
Nasal spray administration (Migranal and generic equivalents)
-Prime the nasal spray device before administration by releasing 4 sprays. Use the spray immediately after priming.
-Do not have patient tilt head back or sniff while spraying or immediately after.
-Spray once in each nostril. Wait 15 minutes, spray once again in each nostril.
-Storage: Discard the nasal spray pump with the vial after use.
Nasal spray administration (Trudhesa)
-Prime the nasal spray device before administration by releasing 4 sprays. Use the spray immediately after priming.
-Make sure the patient's head is straight and the nasal spray device is upright. Sniffing while or after dosing is not necessary; however, it will not cause harm or make the medicine less effective.
-Spray once in each nostril.
-Prepare a new nasal spray device for a second dose, if needed.
-Storage: Discard the assembled nasal spray device immediately after use.
Serious adverse cardiac events, including some that have been fatal, have occurred after use of dihydroergotamine. These events have included acute myocardial infarction, life-threatening disturbances of cardiac rhythm (e.g., ventricular tachycardia and ventricular fibrillation), coronary vasospasm, and transient, acute myocardial ischemia. Dihydroergotamine, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and bowel ischemia have been reported with dihydroergotamine. Dihydroergotamine-associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. Angina and peripheral vasoconstriction have been reported in less than 0.1% of patients during clinical trials of dihydroergotamine. Discontinue dihydroergotamine immediately if signs or symptoms of vasoconstriction develop. Evaluate patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome, after the use of any 5-HT agonist, including dihydroergotamine. Other adverse cardiovascular adverse reactions reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include edema, palpitations, and sinus tachycardia.
Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension treated with dihydroergotamine. Hypotension has been reported in less than 0.1% of patients during clinical trials of dihydroergotamine. Hypertension and flushing have been reported during postmarketing experience with dihydroergotamine.
Intracranial bleeding, including cerebral hemorrhage and subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with dihydroergotamine; some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the dihydroergotamine having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. Discontinue dihydroergotamine if a cerebrovascular event is suspected.
Dizziness (4%), drowsiness (3%), and paresthesias (2%) were among the most commonly reported adverse events during clinical trials of dihydroergotamine. Other central nervous system adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include confusion, tremor, hypoesthesia, and vertigo; speech disorder, hyperkinesis, stupor, gait disturbance, and aggravated migraine were reported in less than 0.1% of patients during clinical trials of dihydroergotamine. Headache has been reported during postmarketing experience with dihydroergotamine. Overuse of drugs for treating acute headaches, including dihydroergotamine, 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 dihydroergotamine 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. Psychiatric adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include nervousness, euphoria, insomnia, and impaired concentration; anxiety, anorexia, and depression were reported in less than 0.1% of patients during clinical trials of dihydroergotamine.
There have been reports of pulmonary fibrosis (pleural) and retroperitoneal fibrosis in patients after prolonged daily use of dihydroergotamine. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis (cardiac valvulopathy). Rare cases have also been reported in association with the use of dihydroergotamine; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis. Do not exceed the dihydroergotamine dosing guidelines and do not use dihydroergotamine for chronic daily administration. Other respiratory adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include dyspnea and upper respiratory tract infection; bronchospasm, bronchitis, and pleural pain were reported in less than 0.1% of patients during clinical trials with dihydroergotamine.
Local nasal irritation or throat irritation symptoms were reported in about 30% to 52% of patients treated with dihydroergotamine nasal spray during clinical trials. The most common local irritative symptoms were nasopharyngitis (21%), rhinitis (19% to 26%), nasal discomfort (7%), dysgeusia (6% to 8%), sinusitis (1% to 5%), sinus discomfort (4%), abnormal olfactory test [defined based on a change in score at a prespecified threshold on the University of Pennsylvania Smell Identification Test (UPSIT)] (4%), epistaxis (3%), pharyngitis (3% or less), nasal mucosal disorder (2%), change in smell (1%), ear discomfort (1%), and rhinorrhea (1%). Other irritative symptoms include nasal congestion, burning sensation, nasal dryness, paraesthesia, discharge, or soreness. Application site reactions were reported in 6% of patients treated with dihydroergotamine nasal spray during clinical trials. Local anesthesia was reported in less than 0.1% of patients during clinical trials of dihydroergotamine. The symptoms were predominantly mild to moderate in severity and transient. In many cases, the symptoms resolved within 4 hours after dosing with dihydroergotamine nasal spray. If a severe local irritation event occurs for no other attributable reasons, temporarily suspend dihydroergotamine nasal spray therapy until the event resolves. If the event does not resolve, or it recurs with re-challenge, discontinue dihydroergotamine nasal spray permanently. Do not exceed dihydroergotamine dosing guidelines and do not use dihydroergotamine for chronic daily administration.
Nausea (10%), vomiting (4%), and diarrhea (2%) were among the most commonly reported adverse events with dihydroergotamine during clinical trials. Xerostomia has been reported in 1% of patients during clinical trials of dihydroergotamine. Other gastrointestinal adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include abdominal pain, dyspepsia, dysphagia, and hiccups; hypersalivation and esophagospasm were reported in less than 0.1% of patients.
Musculoskeletal stiffness has been reported in 1% of patients treated with dihydroergotamine during clinical trials. Other musculoskeletal system adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine include myalgia, muscle cramps, muscular weakness, and dystonic reaction; arthralgia, involuntary muscle contractions, and rigidity were reported in less than 0.1% of patients during clinical trials of dihydroergotamine.
Dermatologic adverse reactions reported in 0.1% to 1% of patients during clinical trials with dihydroergotamine include petechiae, pruritus, rash, and cold clammy skin; maculopapular rash, urticaria, and herpes simplex were reported in less than 0.1% of patients during clinical trials of dihydroergotamine. Hyperhidrosis has been reported during postmarketing experience with dihydroergotamine.
Hot flashes, fatigue, and asthenia have been reported in 1% of patients treated with dihydroergotamine during clinical trials. Other general adverse events reported in 0.1% to 1% of patients during clinical trials with dihydroergotamine include chills, malaise, rigors, fever, periorbital edema; flu-like symptoms, shock, and yawning were reported in less than 0.1% of patients during clinical trials of dihydroergotamine.
Sensory adverse reactions reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine nasal spray include dysosmia, photophobia, conjunctivitis, abnormal lacrimation, visual impairment, tinnitus, and otalgia; loss of voice and ocular pain were reported less than 0.1% of patients during clinical trials of dihydroergotamine nasal spray.
Genitourinary system adverse events reported in 0.1% to 1% of patients during clinical trials of dihydroergotamine nasal spray include cystitis and increased urinary frequency; pelvic inflammation and vaginitis were reported in less than 0.1% of patients during clinical trials of dihydroergotamine nasal spray.
Dihydroergotamine is contraindicated in patients with known ergot alkaloid hypersensitivity.
Dihydroergotamine is contraindicated in patients with basilar/hemiplegic migraine.
Dihydroergotamine is contraindicated in patients with uncontrolled hypertension, peripheral vascular disease, ischemic cardiac disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina (i.e., vasospastic angina). Serious adverse cardiac events, including some that have been fatal, have occurred after dihydroergotamine use. Prior to initiation of dihydroergotamine, a cardiovascular evaluation is recommended to determine if the patient is free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. If, during the cardiovascular evaluation, the patient's medical history (including risk factors), or electrocardiographic investigation, findings are consistent with coronary artery vasospasm or myocardial ischemia, do not administer dihydroergotamine. For patients with risk factors predictive of coronary artery disease (e.g., hypertension, hypercholesterolemia, tobacco smoking, obesity, diabetes mellitus, strong family history of coronary artery disease, postmenopausal females, or males who are older than 40 years) who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of dihydroergotamine take place in the setting of an equipped health care facility, unless the patient has previously received dihydroergotamine. During the interval immediately after the first use of dihydroergotamine, an electrocardiogram is recommended in those patients with risk factors because ischemia can occur in the absence of clinical symptoms. It is recommended that patients who are intermittent long-term users of dihydroergotamine and who have or acquire risk factors predictive of coronary artery disease undergo periodic interval cardiovascular evaluation as they continue to use dihydroergotamine.
Dihydroergotamine is contraindicated in patients with severe hepatic disease.
Dihydroergotamine is contraindicated in patients with severe renal impairment or renal failure.
Dihydroergotamine is contraindicated after vascular surgery and in patients with sepsis.
Avoid dihydroergotamine use during pregnancy. Dihydroergotamine possesses oxytocic properties. Available data indicate an increased risk of preterm delivery with dihydroergotamine use during pregnancy. Data collected over decades have shown no increased risk of major birth defects or miscarriage with use of dihydroergotamine during pregnancy. In animal studies, adverse effects on embryofetal development were observed after administration of dihydroergotamine during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation (decreased body weight and impaired reproductive function in the offspring) in rats at doses less than those used clinically and which were not associated with maternal toxicity.
Because of the potential for reduced milk supply and serious adverse events in the breast-fed infant, advise patients against breast-feeding during treatment with dihydroergotamine and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded. There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of diarrhea, vomiting, weak pulse, and unstable blood pressure in breast-fed infants exposed to ergotamine. Dihydroergotamine may reduce milk supply because it may decrease prolactin concentrations. As a possible alternative, previous American Academy of Pediatrics (AAP) recommendations considered sumatriptan, a serotonin receptor agonist indicated for the treatment of migraines, as usually compatible with breast-feeding.
For the acute treatment of migraine with or without aura:
Intravenous dosage:
Adults: 1 mg IV as a single dose. May repeat dose every 1 hour as needed. Max: 2 mg/day and 6 mg/week. Guidelines classify parenteral dihydroergotamine as having probable efficacy for the treatment of acute migraine.
Adolescents*: Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 1 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.2 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.
Children 10 to 12 years weighing 25 kg or more*: Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 1 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.15 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.
Children 10 to 12 years weighing less than 25 kg*: Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 0.5 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.15 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.
Children 6 to 9 years*: Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 0.5 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.1 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.
Intramuscular or Subcutaneous dosage:
Adults: 1 mg IM or subcutaneously as a single dose. May repeat dose every 1 hour as needed. Max: 3 mg/day and 6 mg/week. Guidelines classify parenteral dihydroergotamine as having probable efficacy for the treatment of acute migraine.
Intranasal dosage (Migranal nasal spray and generic equivalents):
Adults: 0.5 mg in each nostril, followed by 0.5 mg in each nostril 15 minutes later for a total dose of 2 mg. Studies have shown no additional benefit from acute doses more than 2 mg for a single migraine episode. The safety of doses more than 3 mg/day and 4 mg/week have not been established. Guidelines classify intranasal dihydroergotamine as having established efficacy for the treatment of acute migraine.
Intranasal dosage (Trudhesa nasal spray):
Adults: 0.725 mg in each nostril as a single dose. May repeat dose after at least 1 hour after the first dose if needed. Max: 2.9 mg/day and 4.35 mg/week. Guidelines classify intranasal dihydroergotamine as having established efficacy for the treatment of acute migraine.
For the treatment of cluster headache:
Intravenous dosage:
Adults: 1 mg IV once. May repeat dose every 1 hour as needed. Max: 2 mg/day and 6 mg/week.
Intramuscular or Subcutaneous dosage:
Adults: 1 mg IM or subcutaneously once. May repeat dose every 1 hour as needed. Max: 3 mg/day and 6 mg/week.
Maximum Dosage Limits:
-Adults
3 mg/day IM or subcutaneous or 2 mg/day IV and 6 mg/week IV/IM/subcutaneous; 3 mg/day and 4 mg/week intranasal (Migranal and generic equivalents) or 2.9 mg/day and 4.35 mg/week intranasal (Trudhesa).
-Geriatric
3 mg/day IM or subcutaneous or 2 mg/day IV and 6 mg/week IV/IM/subcutaneous; 3 mg/day and 4 mg/week intranasal (Migranal and generic equivalents) or 2.9 mg/day and 4.35 mg/week intranasal (Trudhesa).
-Adolescents
Safety and efficacy have not been established; however, doses up to 1 mg/dose IV or 3 mg/day IV have been used off-label.
-Children
10 to 12 years weighing 25 kg or more: Safety and efficacy have not been established; however, doses up to 1 mg/dose IV or 3 mg/day IV have been used off-label.
10 to 12 years weighing less than 25 kg: Safety and efficacy have not been established; however, doses up to 0.5 mg/dose IV or 1.5 mg/day IV have been used off-label.
6 to 9 years: Safety and efficacy have not been established; however, doses up to 0.5 mg/dose IV or 1.5 mg/day IV have been used off-label.
1 to 5 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use is contraindicated in patients with severe hepatic impairment.
Patients with Renal Impairment Dosing
Use is contraindicated in patients with severe renal impairment.
*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) is potentially increased by the use of CYP3A4 inhibitors. Grapefruit juice may decrease dihydroergotamine metabolism via CYP3A4. Patients should probably use caution with grapefruit juice by not modifying their usual grapefruit juice intake while taking dihydroergotamine. Elderly patients have the greatest possibility of ingesting grapefruit and interacting medications and are the most vulnerable to the adverse clinical consequences. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. 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.
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.
Dihydroergotamine binds with high affinity to 5-HT1D receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, alpha1 and alpha2-adrenergic receptors, and dopamine D2L and D3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5HT1D receptors. It is hypothesized that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. An alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
Dihydroergotamine is administered parenterally or intranasally. Dihydroergotamine is 93% bound to plasma protein, and the apparent steady-state Vd is approximately 800 L. The major metabolite, 8'-beta-hydroxy dihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance. After intranasal administration, total metabolites represent only 20% to 30% of plasma AUC. The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is 1.5 L/minute, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/minute) is unaffected by the route of dihydroergotamine administration. The decline of plasma dihydroergotamine after intramuscular or intravenous administration is multi-exponential with a terminal half-life of about 9 hours. The decline of plasma dihydroergotamine after nasal administration is biphasic with a half-life of about 10 to 12 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Dihydroergotamine is a substrate for CYP3A4.
-Route-Specific Pharmacokinetics
Intravenous Route
After administration of dihydroergotamine 1 mg IV in healthy adults, Tmax was approximately 1 to 2 minutes and Cmax was less than 10 ng/mL.
Intramuscular Route
No difference was observed in dihydroergotamine bioavailability from intramuscular and subcutaneous doses. Bioavailability after intramuscular administration is 100%. After administration of dihydroergotamine 1 mg IM in healthy adults, Tmax was 24 minutes and Cmax was 2.9 ng/mL.
Subcutaneous Route
Absolute bioavailability for subcutaneous administration have not been determined. However, no difference was observed in dihydroergotamine bioavailability from intramuscular and subcutaneous doses.
Other Route(s)
Intranasal Route
Absorption of dihydroergotamine is variable after intranasal administration. Mean bioavailability of dihydroergotamine mesylate is 32% to 40% after intranasal administration relative to injectable administration. Tmax after intranasal administration is approximately 0.5 hours.
-Special Populations
Hepatic Impairment
The effects of hepatic impairment on the pharmacokinetics of dihydroergotamine have not been studied.
Renal Impairment
The effects of renal impairment on the pharmacokinetics of dihydroergotamine have not been studied.
Gender Differences
The effects of gender on the pharmacokinetics of dihydroergotamine have not been studied.
Ethnic Differences
The effects of race on the pharmacokinetics of dihydroergotamine have not been studied.
Other
Pregnancy
The effects of pregnancy on the pharmacokinetics of dihydroergotamine have not been studied.