Mechanism of effect
Efficacy in migraine is attributed to the activation of 5-HT1D receptors located on intracranial blood vessels resulting in vasoconstriction and/or activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system resulting in the inhibition of pro-inflammatory neuropeptide release.
Dihydroergotamine binds with high affinity to serotonin 5-HT1Dα, 5-HT1Dβ, 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors. Dihydroergotamine also possesses oxytocic properties.
Pharmacodynamic
It has similar actions to the triptans, acting as an agonist to the serotonin receptors and causing vasoconstriction of the intracranial blood vessels, but also interacts centrally with dopamine and adrenergic receptors.
Pharmacokinetics
• Distribution: Vd: ~800 L
• Protein binding: 93%
• Metabolism: Extensively hepatic (one active metabolite, 8'-β-hydroxydihydroergotamine)
• Bioavailability: IM, IV: 100%; Intranasal: 40%
• Half-life elimination: ~9 to 10 hours
• Time to peak, serum: IM: 24 minutes; IV: 1 to 2 minutes; Intranasal: 30 to 60 minutes
• Excretion: Primarily feces; urine (6% to 7% as unchanged drug)
Drug indications
MigraineDosage
• 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 into each nostril; repeat after 15 minutes for a total of 4 sprays (2 mg). Safety of doses greater than 6 sprays (3 mg) in a 24-hour period or 8 sprays (4 mg) in a week have not been established. Do not use for chronic daily administration.
• Intractable migraine
• Raskin protocol : Initial: 0.5 mg (following premedication with metoclopramide); subsequent dosing is titrated (range: 0.2 to 1 mg) every 8 hours for up to 7 days . Most patients will be headache-free within 3 days).
• Ford protocol : Following premedication with metoclopramide; 3 mg in 1,000 mL normal saline at 42 mL/hr for up to 7 days (most patients will be headache-free within 3 days). If nausea persists, reduce the rate to 21 to 30 mL/hour.
Interactions
Ergotamine-C , Spiramycin , Ephedrine , Expectorant , Oxymetazoline , Ipratropium bromide , Bupivacaine , Propranolol , Posaconazole , Trazodone , Tranylcypromine , Topiramate , Rizatriptan , Zafirlukast , Sotalol , Sibutramine , Fluvoxamine , Fluoxetine , Metoprolol , Midodrine , Venlafaxine , Carvedilol , Clozapine , Enzalutamide , Disulfiram , Bisoprolol , Rifabutin , Rifapentine , Darunavir , Tapentadol , methylene blue , Norepinephrine , Nefazodone , Almotriptan , Diethylpropion , ritonavir , saquinavir , nelfinavir , eletriptan , Phenylpropanolamine , Amprenavir , Prednisolone , Mifepristone , lisdexamfetamine , brigatinib , Efavirenz , Tipranavir , lumacaftor and Ivacaftor , Etravirine , Desvenlafaxine , Xylometazoline , Propylhexedrine , acrivastine+pseudoephedrine , Darifenacin , Mibefradil , Dexfenfluramine , chlorcyclizine + pseudoephedrine , chlorcyclizine + phenylephrine , Nicardipine , cobicistat , Oxiconazole , Letermovir , Benzphetamine , Butabarbital , Lopinavir and Ritonavir , Levomilnacipran , Lorlatinib , Glycerol Phenylbutyrate , Bromopride , 5-hydroxytryptophan , Roxithromycin , oleandomycin , lasmiditan , Venetoclax , Ombitasvir, Paritaprevir, and Ritonavir , NicotineAlerts
1- 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.
2-Local irritation to nose and throat (usually transient and mild-moderate) can occur; long-term consequences on nasal or respiratory mucosa have not been extensively evaluated.
3- Very bad and sometimes deadly side effects like a heartbeat that does not feel normal, heart attack, stroke, and very bad high blood pressure have happened with this drug.
Points of recommendation
1-If you have an allergy to dihydroergotamine or any other part of this drug , any other drugs, foods;Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
2- If you have high blood pressure or some types of migraine headaches like hemiplegic or basilar migraine, blood vessel problems, chest pain or pressure, heart disease, kidney disease, liver disease, poor blood flow, very bad infection, or recent blood vessel surgery, tell your doctor.
3-If you have taken rizatriptan, sumatriptan, zolmitriptan, ergotamine or methysergide in the last 24 hours.
4- Do not take this drug if you are pregnant, may be pregnant orbreast-feeding.
5-If you drink grapefruit juice, talk with your doctor.
6- This drug is not meant for regular, daily use.
7- Injection is given as a shot into a muscle or into the fatty part of the skin.
8- Do not use if the injection solution is cloudy, leaking, changes color or has particles.
9- Wash your hands before and after use injection.
10- In nose spray prime pump by squeezing it 4 times. Breathe in 1 spray in each nostril. Wait 15 minutes. Breathe in 1 more spray in each nostril.
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