(dye hye droe er GOT a meen)
Treatment of migraine headache with or without aura; injection also indicated for treatment of cluster headaches
Hypersensitivity to dihydroergotamine or any component of the formulation; uncontrolled hypertension, ischemic heart disease, angina pectoris, history of MI, silent ischemia, or coronary artery vasospasm including Prinzmetals angina; hemiplegic or basilar migraine; peripheral vascular disease; sepsis; severe hepatic or renal dysfunction; following vascular surgery; avoid use within 24 hours of sumatriptan, zolmitriptan, other serotonin agonists, or ergot-like agents; avoid during or within 2 weeks of discontinuing MAO inhibitors; concurrent use of peripheral and central vasoconstrictors; ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); pregnancy, breast-feeding
Serious and life-threatening peripheral ischemia have been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.
Migraine, cluster headache:
IM, SubQ: 1 mg at first sign of headache; repeat hourly to a maximum dose of 3 mg/day; maximum dose: 6 mg/week
IV: 1 mg at first sign of headache; repeat hourly up to a maximum dose of 2 mg/day; maximum dose: 6 mg/week
Intranasal: 1 spray (0.5 mg) of nasal spray should be administered into each nostril; if needed, repeat after 15 minutes, up to a total of 4 sprays (2 mg). Note: Do not exceed 6 sprays (3 mg) in a 24-hour period and no more than 8 sprays (4 mg) in a week.
Intractable migraine (status migrainosus; >72 hours): IV: Raskin protocol (off-label dosing): Initial test dose: 0.5 mg (following premedication with metoclopramide); subsequent dosing is titrated (range: 0.2-1 mg) every 8 hours for 2-3 days and administered with or without metoclopramide based on response and tolerance (Raskin, 1986; Raskin, 1990). Note: Some clinicians use modified versions of this protocol, with additional adjunctive medications and/or alternate antiemetic agents.
Refer to adult dosing. Patients >65 years of age were not included in controlled clinical studies.
Contraindicated in severe renal impairment
Dosage reductions are probably necessary but specific guidelines are not available; contraindicated in severe hepatic dysfunction.
Intranasal: Prior to administration of nasal spray, the nasal spray applicator must be primed (pumped 4 times); in order to let the drug be absorbed through the skin in the nose, patients should not inhale deeply through the nose while spraying or immediately after spraying; for best results, treatment should be initiated at the first symptom or sign of an attack; however, nasal spray can be used at any stage of a migraine attack.
IM, SubQ: May administer by intramuscular or subcutaneous injection.
IV: Administer slowly over 2-3 minutes (Raskin protocol)
Injection: Store below 25 ‚ °C (77 ‚ °F); do not refrigerate or freeze; protect from heat. Protect from light.
Nasal spray: Prior to use, store below 25 ‚ °C (77 ‚ °F); do not refrigerate or freeze. Once spray applicator has been prepared, use within 8 hours; discard any unused solution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as mesylate:
D.H.E. 45: 1 mg/mL (1 mL)
Generic: 1 mg/mL (1 mL)
Solution, Nasal, as mesylate:
Migranal: 4 mg/mL (1 mL)
Generic: 4 mg/mL (1 mL)
Alpha-/Beta-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Avoid combination
Alpha1-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Avoid combination
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Ergot Derivatives. Avoid combination
Anti-Parkinson Agents (Monoamine Oxidase Inhibitor): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if selegiline or rasagiline is combined with a serotonin modulator. Use of transdermal selegiline with serotonin modulators is contraindicated. Consider therapy modification
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives. Consider therapy modification
Boceprevir: May increase the serum concentration of Dihydroergotamine. Avoid combination
Clarithromycin: May increase the serum concentration of Dihydroergotamine. Avoid combination
Cobicistat: May increase the serum concentration of Dihydroergotamine. Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Crizotinib: May increase the serum concentration of Dihydroergotamine. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Enzalutamide: May decrease the serum concentration of Dihydroergotamine. Avoid combination
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Itraconazole: May increase the serum concentration of Dihydroergotamine. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Dihydroergotamine. Avoid combination
Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Consider therapy modification
Lorcaserin: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Consider therapy modification
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
MiFEPRIStone: May increase the serum concentration of Dihydroergotamine. Management: Avoid dihydroergotamine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushings syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Posaconazole: May increase the serum concentration of Dihydroergotamine. Avoid combination
Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Avoid combination
Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. Monitor therapy
Roxithromycin: May increase the serum concentration of Ergot Derivatives. Avoid combination
Serotonin 5-HT1D Receptor Agonists: Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Telaprevir: May increase the serum concentration of Dihydroergotamine. Avoid combination
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Voriconazole: May increase the serum concentration of Dihydroergotamine. Avoid combination
>10%: Nasal spray: Respiratory: Rhinitis (26%)
1% to 10%: Nasal spray:
Central nervous system: Taste disorder (8%), dizziness (4%), drowsiness (3%)
Endocrine & metabolic: Hot flash (1%)
Gastrointestinal: Nausea (10%), vomiting (4%), diarrhea (2%)
Local: Application site reaction (6%)
Neuromuscular & skeletal: Stiffness (1%), weakness (1%)
Respiratory: Pharyngitis (3%)
<1% (Limited to important or life-threatening): Injection and nasal spray: Abdominal pain, anxiety, cerebral hemorrhage, cerebrovascular accident, coronary artery vasospasm, diaphoresis, diarrhea, dizziness, dyspnea, edema, fibrothorax (prolonged use), flushing, headache, hyperkinesia, hypertension, ischemic heart disease, muscle cramps, myalgia, myasthenia, myocardial infarction, palpitations, paresthesia, peripheral cyanosis, peripheral ischemia, retroperitoneal fibrosis (prolonged use), skin rash, subarachnoid hemorrhage, tremor, valvular sclerosis (associated with ergot alkaloids), ventricular fibrillation, ventricular tachycardia (transient)
Concerns related to adverse effects:
- Cardiac valvular fibrosis: Ergot alkaloids have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
- Cardiovascular effects: Vasospasm or vasoconstriction can occur, possibly resulting in decreased cerebral blood flow, ECG changes, and hypertension; sustained vasoconstriction may also lead to ischemic colitis, intermittent claudication, aggravation of angina, or precipitation of MI. Do not use is any patient at risk or predisposed to vascular effects of ergot alkaloids.
- Cerebrovascular events: Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have also occurred (in some cases resulted in fatalities) following use of the injection.
- Ergotism: Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration.
- Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.
Disease-related concerns:
- Cardiovascular disease: Do not give to patients with risk factors for CAD until a cardiovascular evaluation has been performed; if evaluation is satisfactory, the healthcare provider should administer the first dose and cardiovascular status should be periodically evaluated.
Concurrent drug therapy issues:
- CYP3A4 inhibitors: [U.S. Boxed Warning]: Ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); concomitant use associated with an increased risk of vasospasm leading to cerebral ischemia and/or ischemia of the extremities.
Special populations:
- Elderly: Use with extreme caution or avoid use in the elderly; due to vasoconstrictive properties and cardiovascular adverse effects associated with ergot alkaloids.
Dosage form specific issues:
- Migranal ‚ ® Nasal Spray: Local irritation to nose and throat (usually transient and mild-moderate in severity) can occur; long-term consequences on nasal or respiratory mucosa have not been extensively evaluated.
X
Dihydroergotamine is oxytocic and should not be used during pregnancy.
Ergot alkaloid alpha-adrenergic blocker directly stimulates vascular smooth muscle to vasoconstrict peripheral and cerebral vessels; also has effects on serotonin receptors
Vd: ~800 L
Extensively hepatic (one active metabolite)
Primarily feces; urine (6% to 7% as unchanged drug); Clearance: 1.5 mL/minute
IM: 15-30 minutes
Serum: IM: 24 minutes; IV: 1-2 minutes; Intranasal: 30-60 minutes; SubQ 15-45 minutes
IM: 3-4 hours
~9-10 hours
93%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, rhinitis, pharyngitis, change in taste, nosebleed, or rhinorrhea. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, tachycardia, burning or numbness feeling, severe dizziness, passing out, muscle pain, weakness, muscle cramps, arrhythmia, change in color of hands or feet from pale to blue or red, sensation of cold, bradycardia, edema, or severe abdominal pain (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.