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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Ergot Alkaloids

Last Update: February 10, 2018.



Ergot alkaloids are widely used for therapy of acute migraine headaches and include ergotamine and dihydroergotamine, both of which act by causing vasoconstriction of the carotid artery beds. Ergot alkaloids have multiple side effects, but have little effect on the liver and have not been clearly linked to instances of clinically apparent acute liver injury.


Ergotamine (er got' a meen) and dihydroergotamine are ergot alkaloids that act as vasoconstrictors, probably by stimulating alpha adrenergic receptors particularly in the carotid artery bed. The ergotamines may also have serotoninergic effects which may also be beneficial in migraine. The ergotamines were first reported to alleviate migraine headaches in the 1920s and were introduced into clinical use in the United States in the 1940s. Ergotamine is available in 1 mg tablets in multiple generic forms and under brand names such as Cafergot, Ergomar, Ergostat, Migergot and Wigraine. Various combinations of ergotamine with caffeine (100 mg) and acetaminophen are also available as are rectal suppositories (2 mg with or without caffeine) and sublingual forms (2 mg). The usual recommended dose to abort or treat a vascular headache is 2 mg initially (sublingually or orally) and then 1 to 2 mg every 30 minutes, to a maximum of 6 mg per attack and 10 mg weekly. Dihydroergotamine is available in solution for injection (1 mg/mL) or as a nasal spray (4 mg/mL) in generic forms and under the brand names of DHE 45 and Migranal. The usual recommended dose is 1 mg intramuscularly or intravenously initially, repeated at 1 hour intervals to a total dose of 2 to 3 mg and no more than 6 mg weekly. The nasal spray is given as 0.5 mg to each nostril, repeated every 15 minutes, but to less than 3 mg in 24 hours and 4 mg in one week. The advantage of the nasal and parenteral formulations is the rapid onset of action; the disadvantage is a greater potential for overdose or side effects. Common side effects (ergotism) include nausea, vomiting, light-headedness, numbness and tingling, hypertension, bradycardia, muscle pains and itching. Overdose can cause acute vascular spasm and thrombosis.


Neither ergotamine nor dihydroergotamine have been implicated in causing liver enzyme elevations, but they are generally used in limited amounts for short and intermittent periods of time. Ergotamine abuse can lead to arterial or venous spastic episodes, and at least one case of portal and splenic vein thrombosis with resultant noncirrhotic portal hypertension has been reported. Ergotamine overdose can lead to ischemic injury to limbs or viscera, including the liver. However, the ergotamines have not been implicated in cases of clinically apparent liver injury and product labels do not mention ALT elevations or liver injury as potential adverse events.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Ergotamine is extensively metabolized by the liver, but it is given in low doses, and intermediates of its metabolism, even if potentially toxic, are likely conjugated and excreted rapidly and without hepatic injury. The vasospastic actions of ergotamines can cause arterial and venous spasms and potentially thromboses to the hepatic artery or portal systems.

Agents used specifically in management of migraines and vascular headaches include: the ergot alkaloids, ergotamine and dihydroergotamine; and, the serotonin receptor agonists (triptans), including almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan.

Drug Class: Migraine Headache Agents, Vasoconstrictor Agents



Dihydroergotamine – Generic, Migranal®

Ergotamine – Generic, Cafergot®


Migraine Headache Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Dihydroergotamine Chemical Structure
Ergotamine Chemical Structure


References updated: 10 February 2018

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    (Expert review of hepatotoxicity published in 1999; ergotamine and triptans are not discussed).
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    Corrected and republished in: JAMA 2017; 317 (21): 2230-1. PubMed Citation (Concise review of current medications used for migraine; no discussion of hepatotoxicity).


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