Active ingredient: Dihydroergotamine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Analgesics
• Vasoconstrictor Agents
• Sympatholytics

Dosage Forms

• Liquid

Brands / Synonyms

Agit; Angionorm; D.H.E.; D.h.e. 45; Dergotamine; DET MS; DHE-45; Diergo; Dihidroergotamina [INN-Spanish]; Dihydergot; Dihydroergotamine mesylate; Dihydroergotamine methanesulfonate; Dihydroergotamine monomethanesulfonate; Dihydroergotaminum [INN-Latin]; Dirgotarl; Endophleban; Ergomimet; Ergont; Ergotamine, 9,10-dihydro-; Ergotonin; Ikaran; Migranal; Morena; Orstanorm; Tonopres; Verladyn

Indications

For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

Pharmacology

Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Dihydroergotamine binds with high affinity to 5-HT_1Da and 5-HT_1Db receptors. It also binds with high affinity to serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors, noradrenaline a2A, a2B and a receptors, and dopamine D2L and D3 receptors. The therapeutic activity of Dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT_1D receptors.

Mechanism of Action

Two theories have been proposed to explain the efficacy of 5-HT_1D receptor agonists in migraine: 1) activation of 5-HT_1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache and 2) activation of 5-HT_1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

Absorption

Interpatient variable and may be dependent on the administration technique

Toxicity

Side effects include abdominal pain, abnormal speech, coma, confusion, convulsions, hallucinations, increase and/or decrease in blood pressure, nausea, numbness, tingling, pain, and a bluish color of your fingersand toes, slowed breathing, vomiting

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

Dihydroergotamine Injection should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina. Because Dihydroergotamine may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Dihydroergotamine, 5-HT1 agonists (e.g., sumatriptan) ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other. Dihydroergotamine should not be administered to patients with hemiplegic or basilar migraine. In addition to those conditions mentioned above, Dihydroergotamine is also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery and severely impaired hepatic or renal function. Dihydroergotamine may cause fetal harm when administered to a pregnant woman. Dihydroergotamine possesses oxytocic properties and therefore, should not be administered during pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. There are no adequate studies of dihydroergotamine in human pregnancy, but developmental toxicity has been demonstrated in experimental animals. In embryo-fetal development studies of dihydroergotamine mesylate nasal spray, intranasal administration to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weights and/or skeletal ossification at doses of 0.16 mg/day (associated with maternal plasma dihydroergotamine exposures [AUC] approximately 0.4-1.2 times the exposures in humans receiving the MADE of 4 mg) or greater. A no effect level for embryo-fetal toxicity was not established in rats. Delayed skeletal ossification was also noted in rabbit fetuses following intranasal administration of 3.6 mg/day (maternal exposures approximately 7 times human exposures at the MRDD) during organogenesis. A no effect level was seen at 1.2 mg/day (maternal exposures approximately 2.5 times human exposures at the MRDD). When dihydroergotamine mesylate nasal spray was administered intranasally to female rats during pregnancy and lactation, decreased body weights and impaired reproductive function (decreased mating indices) were observed in the offspring at doses of 0.16 mg/day or greater. A no effect level was not established. Effects on development occurred at doses below those that produced evidence of significant maternal toxicity in these studies. Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone. Dihydroergotamine is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids. Dihydroergotamine mesylate should not be used by nursing mothers. Dihydroergotamine mesylate should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.

Drug Interactions

Vasoconstrictors: D.H.E. 45 (dihydroergotamine mesylate) injection, USP should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure.

Sumatriptan: Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with D.H.E. 45 (dihydroergotamine mesylate) injection, USP. Sumatriptan and D.H.E. 45 (dihydroergotamine mesylate) injection, USP should not be taken within 24 hours of each other.

Beta Blockers: Although the results of a clinical study did not indicate a safe problem associated with the administration of D.H.E. 45 (dihydroergotamine mesylate) injection, USP to subjects already receiving propranolol, there have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

Nicotine: Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.

Macrolide Antibiotics (e. g. erythromycin and troleandomycin): Agents of the ergot alkaloid class, of which D.H.E. 45 (dihydroergotamine mesylate) injection, USP is a member, have been shown to interact with antibiotics of the macrolide class, resulting in increased plasma levels of unchanged alkaloids and peripheral vasoconstriction. Vasospastic reactions have been reported with therapeutic doses of ergotamine-containing drugs when co-administered with these antibiotics.

SSRI's: Weakness hyperreflexia, and incoordination have been reported rarely when 5-HT1 agonists have been co-administered with SSRI's (e.g. fluoxetine, fluvoxamine, paroxetine, sertraline). There have been no reported cases from spontaneous reports of drug interaction between SSRI's and D.H.E. 45 (dihydroergotamine mesylate) injection, USP.

Oral Contraceptives: The effect of oral contraceptives on the pharmacokinetics of D.H.E. 45 (dihydroergotamine mesylate) injection, USP has not been studied.