WIGRAINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).

How it works

WIGRAINE is a combination product containing ergotamine, a vasoconstrictor that acts as an agonist at serotonin (5-HT1B/1D) and alpha-adrenergic receptors, and caffeine, which enhances ergotamine absorption and provides additional vasoconstriction.

What the body does with it

Metabolism	Ergotamine is extensively metabolized in the liver via CYP3A4; caffeine is primarily metabolized by CYP1A2.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites. ~90% urinary, ~10% fecal.
Half-life	Ergotamine: ~2-3 hours (terminal). Clinical context: short half-life necessitates frequent dosing for acute migraine relief.
Protein binding	~90% bound to plasma proteins (albumin).
Volume of Distribution	Ergotamine: ~1.4 L/kg (large Vd indicating extensive tissue distribution).
Bioavailability	Oral: <5% due to extensive first-pass metabolism; rectal: ~30-40%.
Onset of Action	Oral: 0.5-2 hours. Rectal: 15-30 minutes.
Duration of Action	Oral: ~4 hours; Rectal: up to 6 hours. Note: vasoconstrictive effects may persist longer.

Classification & Brands

Dosing & administration

For acute migraine: 2 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) orally at onset, then 1 tablet every 30 minutes as needed, maximum 6 tablets per attack, maximum 10 tablets per week.

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-50 mL/min), use with caution and reduce dose by 50%; no adjustment needed for mild impairment (CrCl >50 mL/min).
Liver impairment	Contraindicated in Child-Pugh class C. In Child-Pugh class B, reduce dose by 50% and monitor for signs of toxicity. No adjustment needed for Child-Pugh class A.
Pediatric use	Not recommended for children under 12 years. For adolescents 12-17 years: 1 tablet at onset, may repeat after 30 minutes if needed; maximum 2 tablets per attack, maximum 4 tablets per week.
Geriatric use	Use lower starting dose (1 tablet) due to increased sensitivity and risk of adverse effects. Monitor for peripheral ischemia and cardiac effects; maximum 4 tablets per week.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).

Breastfeeding	Contraindicated; ergotamine is excreted into breast milk with M/P ratio approximately 0.6. Potential for ergotism in infants (vomiting, diarrhea, seizures). Avoid breastfeeding within 48 hours of last dose.
Teratogenic Risk	First trimester: Limited human data; ergotamine tartrate is oxytocic and may cause uterine contractions, fetal hypoxia, and growth restriction. Second and third trimesters: Contraindicated due to risk of preterm labor, placental insufficiency, and fetal death. Ergot alkaloids are FDA Category X.

Warnings & precautions

■ FDA Black Box Warning

Serious and/or life-threatening peripheral ischemia has been associated with coadministration of ergotamine with potent CYP3A4 inhibitors including protease inhibitors, macrolide antibiotics, and azole antifungals.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to ergot alkaloids or caffeine","Concurrent use of potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors, azole antifungals)","Peripheral vascular disease","Coronary artery disease","Uncontrolled hypertension","Sepsis","Severe hepatic or renal impairment","Pregnancy","Lactation"]

Clinical Precautions

Precautions

["Risk of ischemic events including myocardial ischemia, peripheral vascular ischemia, and cerebrovascular ischemia","Fetal harm (Pregnancy Category X)","Coronary artery disease risk in patients with risk factors","Retroperitoneal and pleuropulmonary fibrosis","Reye's syndrome-like effects in children with vomiting","Ergotism with prolonged use or overdose","Serotonin syndrome when combined with other serotonergic drugs"]

Clinical Tips & Counseling

Drug interactions

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WIGRAINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).

How it works

What the body does with it

Metabolism	Ergotamine is extensively metabolized in the liver via CYP3A4; caffeine is primarily metabolized by CYP1A2.
Excretion	Primarily hepatic metabolism; renal excretion of metabolites. ~90% urinary, ~10% fecal.
Half-life	Ergotamine: ~2-3 hours (terminal). Clinical context: short half-life necessitates frequent dosing for acute migraine relief.
Protein binding	~90% bound to plasma proteins (albumin).
Volume of Distribution	Ergotamine: ~1.4 L/kg (large Vd indicating extensive tissue distribution).
Bioavailability	Oral: <5% due to extensive first-pass metabolism; rectal: ~30-40%.
Onset of Action	Oral: 0.5-2 hours. Rectal: 15-30 minutes.
Duration of Action	Oral: ~4 hours; Rectal: up to 6 hours. Note: vasoconstrictive effects may persist longer.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-50 mL/min), use with caution and reduce dose by 50%; no adjustment needed for mild impairment (CrCl >50 mL/min).
Liver impairment	Contraindicated in Child-Pugh class C. In Child-Pugh class B, reduce dose by 50% and monitor for signs of toxicity. No adjustment needed for Child-Pugh class A.
Pediatric use	Not recommended for children under 12 years. For adolescents 12-17 years: 1 tablet at onset, may repeat after 30 minutes if needed; maximum 2 tablets per attack, maximum 4 tablets per week.
Geriatric use	Use lower starting dose (1 tablet) due to increased sensitivity and risk of adverse effects. Monitor for peripheral ischemia and cardiac effects; maximum 4 tablets per week.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).

Breastfeeding	Contraindicated; ergotamine is excreted into breast milk with M/P ratio approximately 0.6. Potential for ergotism in infants (vomiting, diarrhea, seizures). Avoid breastfeeding within 48 hours of last dose.
Teratogenic Risk	First trimester: Limited human data; ergotamine tartrate is oxytocic and may cause uterine contractions, fetal hypoxia, and growth restriction. Second and third trimesters: Contraindicated due to risk of preterm labor, placental insufficiency, and fetal death. Ergot alkaloids are FDA Category X.