indication

For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia".

pharmacology

Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.

mechanism of action

Ergotamine acts on migraine by one of two proposed mechanisms: 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.

toxicity

Signs of overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion.

biotransformation

Hepatic. Ergotamine is metabolized by the liver by largely undefined pathways, and 90% of the metabolites are excreted in the bile.

absorption

The bioavailability of sublingually administered ergotamine has not been determined.

half life

2 hours

drug interactions

Acebutolol: Ischemia with risk of gangrene

Almotriptan: Possible severe and prolonged vasoconstriction

Amprenavir: Amprenavir may increase the effect and toxicity of ergotamine.

Amyl Nitrite: Possible antagonism of action

Atazanavir: Atazanavir may increase the effect and toxicity of ergotamine.

Atenolol: Ischemia with risk of gangrene

Betaxolol: Ischemia with risk of gangrene

Bevantolol: Ischemia with risk of gangrene

Bisoprolol: Ischemia with risk of gangrene

Carteolol: Ischemia with risk of gangrene

Carvedilol: Ischemia with risk of gangrene

Clarithromycin: Risk of ergotism and severe ischemia with this association

Delavirdine: The antiretroviral agent may increase the ergot derivative toxicity

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Efavirenz: The antiretroviral agent may increase the ergot derivative toxicity

Eletriptan: Possible severe and prolonged vasoconstriction

Erythrityl Tetranitrate: Possible antagonism of action

Erythromycin: Possible ergotism and severe ischemia with this combination

Esmolol: Ischemia with risk of gangrene

Fluconazole: Possible ergotism and severe ischemia with this combination

Fluoxetine: Possible ergotism and severe ischemia with this combination

Fluvoxamine: Possible ergotism and severe ischemia with this combination

Fosamprenavir: Amprenavir increases the effect and toxicity of ergot derivative

Frovatriptan: Possible severe and prolonged vasoconstriction

Indinavir: Indinavir may increase the serum concentration of ergotamine. Concomitant therapy is contraindicated.

Isosorbide Dinitrate: Possible antagonism of action

Isosorbide Mononitrate: Possible antagonism of action

Itraconazole: Possible ergotism and severe ischemia with this combination

Josamycin: Possible ergotism and severe ischemia with this combination

Ketoconazole: Possible ergotism and severe ischemia with this combination.

Labetalol: Ischemia with risk of gangrene

Metoprolol: Ischemia with risk of gangrene

Nadolol: Ischemia with risk of gangrene

Naratriptan: Possible severe and prolonged vasoconstriction.

Nefazodone: Possible ergotism and severe ischemia with this combination

Nelfinavir: Nelfinavir increases the effect and toxicity of ergot derivative

Nitroglycerin: Possible antagonism of action

Oxprenolol: Ischemia with risk of gangrene

Penbutolol: Ischemia with risk of gangrene

Pindolol: Ischemia with risk of gangrene

Posaconazole: Contraindicated co-administration

Practolol: Ischemia with risk of gangrene

Propranolol: Ischemia with risk of gangrene

Ritonavir: The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, ergotamine.

Rizatriptan: Possible severe and prolonged vasoconstriction

Saquinavir: The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, ergotamine.

Sibutramine: Possible serotoninergic syndrome with this combination

Sotalol: Ischemia with risk of gangrene

Sumatriptan: Possible severe and prolonged vasoconstriction

Telithromycin: Telithromycin may reduce clearance of Ergotamine. Concomitant therapy is contraindicated.

Timolol: Ischemia with risk of gangrene

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Ergotamine. Concomitant therapy is contraindicated.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Troleandomycin: Possible ergotism and severe ischemia with this combination

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ergotamine by decreasing its metabolism. Concomitant therapy is contraindicated.

Zileuton: Possible ergotism and severe ischemia with this combination

Zolmitriptan: Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, ergotamine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.