WIGRAINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).
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.
| 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. |
| Molecular Weight | 581.66 |
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. |
| 1st trimester | Avoid. Contains ergotamine, which is contraindicated in pregnancy due to oxytocic effects and risk of fetal harm. |
| 2nd trimester | Avoid. Ergotamine can cause uterine contractions and reduce placental blood flow. |
| 3rd trimester | Avoid. Ergotamine can induce premature labor and cause neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for WIGRAINE (WIGRAINE).
| Placental transfer | Ergotamine crosses the placenta (documented in animal studies; human data limited but assumed due to small molecular weight). |
| Breastfeeding | Ergotamine is excreted into breast milk and may cause ergotism in the infant (vomiting, diarrhea, convulsions). Breastfeeding is not recommended during use. |
| Lactation Rating |
■ 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.
| Serious Effects |
PregnancyHypersensitivity to ergot alkaloidsCoronary artery diseaseSevere hypertensionPeripheral vascular diseaseSevere hepatic or renal impairmentConcomitant use with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors)
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment (potent CYP3A4 inhibition increases ergotamine toxicity). Concomitant intake of caffeine-containing beverages may exacerbate cardiovascular side effects (tachycardia, hypertension). Nicotine (smoking) enhances vasospasm risk; advise cessation. |
Loading safety data…
| L5 |
| 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. |
| Fetal Monitoring | Monitor uterine activity, fetal heart rate (nonstress test) and growth (serial ultrasound) if inadvertent use during pregnancy. Assess maternal blood pressure and signs of ergotism (numbness, tingling, chest pain). |
| Fertility Effects | May impair female fertility due to vasoconstriction of uterine and ovarian vessels; reduced conception rates reported. No data on male fertility. |
| Clinical Pearls | Wigraine (ergotamine tartrate 1 mg + caffeine 100 mg) is first-line for acute migraine with prolonged aura or status migrainosus. Administer at first sign of attack; sublingual route bypasses first-pass metabolism. Avoid in coronary artery disease, uncontrolled hypertension, and pregnancy (category X). Max per attack: 2 tablets; max per week: 5 days (10 tablets) to avoid ergotism. Concomitant triptans or CYP3A4 inhibitors (e.g., macrolides, azoles) increase vasospasm risk. |
| Patient Advice | Take Wigraine at the very first symptom of migraine, not for prevention. · Place one tablet under the tongue and let it dissolve; do not swallow or chew. · Do not take more than 2 tablets per attack or 10 tablets per week to avoid serious side effects. · Avoid using Wigraine within 24 hours of another triptan (e.g., sumatriptan) or ergotamine product. · Stop taking Wigraine and seek emergency care if you experience chest pain, difficulty breathing, or numbness in fingers/toes. · Do not drink grapefruit juice while using Wigraine; it can increase drug levels. · Keep Wigraine out of reach of children and away from heat/moisture. |