Ergotamine

BRAND NAMES

• Cafergot (Ergotamine + Caffeine)

• Ergomar

• Wigraine

• Migergot

• Ergotamine tartrate (generic forms)

MECHANISM OF ACTION

Ergotamine works by stimulating alpha-1 adrenergic receptors, leading to constriction of dilated cranial and cerebral blood vessels, which helps relieve migraine pain. It also inhibits the transmission of pain signals in the trigeminal nerve pathways. The combination with caffeine enhances vascular constriction and absorption. Ergotamine has partial agonist activity at serotonin receptors (5-HT1B/1D), contributing to its anti-migraine effect. Its activity is dose-dependent, and excessive use can lead to vasospasm.

PHARMACOKINETICS

Absorption:

Ergotamine is poorly absorbed orally, and its bioavailability is highly variable. Co-administration with caffeine improves gastrointestinal absorption. Peak plasma levels occur within 30–60 minutes after oral intake. Sublingual or rectal forms bypass first-pass metabolism and act faster.

Distribution:

Once absorbed, ergotamine binds extensively to plasma proteins and distributes to vascular tissues and the CNS, where it exerts its therapeutic effects. It crosses the placenta but does not readily cross the blood-brain barrier in large amounts.

Metabolism:

Ergotamine undergoes extensive hepatic metabolism, primarily by CYP3A4 enzymes. Metabolites have minimal pharmacologic activity. Impaired liver function can significantly alter its metabolism and increase toxicity risk.

Excretion:

Excretion occurs mainly through bile and feces, with less than 5% eliminated in urine. Its half-life varies depending on formulation and route of administration.

PHARMACODYNAMICS

Ergotamine acts as a vasoconstrictor, reducing the dilation of cranial blood vessels that contribute to migraine pain. It also affects serotonergic and adrenergic pathways, diminishing trigeminal nerve-mediated pain transmission. Its effect is dose-dependent, and repeated use can lead to tolerance or rebound headaches. The combination with caffeine enhances its therapeutic effect and speeds absorption.

ADMINISTRATION

Ergotamine is available as oral tablets, sublingual tablets, and rectal suppositories. It should be taken at the onset of a migraine attack and under medical supervision. Frequent or prophylactic use is generally avoided due to risk of vasospasm and dependence. Dosing intervals must follow strict guidelines to prevent overdose or ergotism.

DOSAGE AND STRENGTH

Typical adult oral doses are 1–2 mg at the onset of a migraine, with a maximum of 6 mg in 24 hours. Sublingual forms are 1 mg per tablet, and rectal suppositories are usually 2 mg. Doses are individualized based on severity and patient tolerance. Elderly patients or those with hepatic/renal impairment require dose adjustments.

DRUG INTERACTIONS

Ergotamine interacts with CYP3A4 inhibitors (e.g., macrolides, protease inhibitors), which can lead to severe vasospasm or ergot toxicity. Concomitant use with triptans or other vasoconstrictors is contraindicated. Other medications affecting blood pressure or vascular tone may amplify its effects. Always inform healthcare providers of current medications before starting ergotamine.

FOOD INTERACTIONS

Food has minimal effect on ergotamine absorption, but taking it with caffeine enhances oral absorption. Grapefruit juice and other CYP3A4-modulating foods should be avoided as they may increase toxicity risk. Adequate hydration may reduce gastrointestinal irritation during oral therapy.

CONTRAINDICATIONS

Ergotamine is contraindicated in patients with:

• Peripheral vascular disease or coronary artery disease

• Severe hypertension or ischemic heart disease

• Pregnancy (can induce uterine contractions)

• Renal or hepatic impairment

• Known hypersensitivity to ergot derivative

SIDE EFFECTS

• Nausea, vomiting, and diarrhea

• Abdominal pain and cramps

• Dizziness or headache exacerbation

• Cold extremities, numbness, or tingling

• Rare: severe vasospasm, myocardial ischemia, or ergotism

OVER DOSE

Ergotamine overdose can cause severe vasospasm, leading to ischemia of the extremities or vital organs. Symptoms include nausea, vomiting, abdominal pain, hypertension, and bradycardia. Treatment involves discontinuation of the drug, supportive care, and vasodilators if needed. Rapid medical attention is essential to prevent permanent tissue damage.

TOXICITY

Ergotamine has a narrow therapeutic index, and toxicity is primarily vascular, resulting from excessive vasoconstriction. Chronic overuse may lead to ergotism, characterized by gangrene, severe hypertension, or cardiac ischemia. Acute toxicity can be managed with symptomatic and supportive care, but caution is necessary due to its high potency. Safe use requires adherence to recommended doses and strict monitoring.