ZOMIG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOMIG (ZOMIG).
Selective 5-HT1B/1D receptor agonist; constricts cranial blood vessels and inhibits trigeminal nerve transmission.
| Metabolism | Hepatic via CYP1A2; also metabolized by monoamine oxidase A (MAO-A). |
| Excretion | Primarily hepatic metabolism via CYP1A2; approximately 10-15% excreted unchanged in urine, with the remainder eliminated as metabolites (mostly N-desmethylzolmitriptan and indoleacetic acid) in urine (60%) and feces (30%). |
| Half-life | Mean terminal elimination half-life is approximately 3 hours (range 2.5-4 hours). In patients with hepatic impairment, half-life may be prolonged (up to 7 hours). |
| Protein binding | 25% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 6-7 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 40-46% (mean 40%) due to first-pass metabolism. Absolute bioavailability of intranasal route is similar (about 40%). |
| Onset of Action | Oral: Onset of headache relief within 30 minutes to 1 hour; orally disintegrating tablet (ODT) similar. Intranasal: Onset as early as 15 minutes, with significant relief by 30 minutes. |
| Duration of Action | Duration of action is 2-4 hours, with a single 2.5 mg oral dose providing relief for up to 4 hours; recurrence of headache may occur within 24 hours, requiring repeat dosing but not exceeding 10 mg/day. |
| Molecular Weight | 287.36 |
2.5 mg orally at onset of migraine; may repeat after 2 hours if needed, maximum 10 mg in 24 hours. Also available as 5 mg nasal spray and 3 mg subcutaneous injection.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based adjustments recommended; use with caution in severe renal impairment (CrCl <15 mL/min) due to limited data. |
| Liver impairment | Child-Pugh Class A or B: 2.5 mg orally at onset, maximum 5 mg in 24 hours; Child-Pugh Class C: contraindicated. |
| Pediatric use | Not approved for pediatric patients <18 years; safety and efficacy not established. |
| Geriatric use | No specific dosing adjustments; use with caution due to potential for increased sensitivity, renal impairment, and cardiovascular risk factors. |
| 1st trimester | Limited human data; animal studies show teratogenicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | No adequate human studies; potential for uterine contractions and reduced placental blood flow. |
| 3rd trimester | May cause uterine contractions and premature labor; avoid use near term unless clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for ZOMIG (ZOMIG).
| Placental transfer | Zolmitriptan crosses the placenta in humans; fetal plasma concentrations are approximately 30% of maternal levels. |
| Breastfeeding | Zolmitriptan is excreted in human milk in small amounts; relative infant dose <2%. Use with caution, monitor infant for diarrhea, vomiting, or restlessness. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Ischemic heart diseasePrinzmetal's anginaUncontrolled hypertensionHemiplegic or basilar migraineRecent stroke or TIAConcomitant use of MAO-A inhibitors or within 2 weeks of discontinuation
| Precautions | Serotonin syndrome (especially with SSRIs/SNRIs), Coronary vasospasm risk (contraindicated in ischemic heart disease), Stroke risk in patients with risk factors, Increase in blood pressure, Rare but serious cardiac events, Dependence potential with overuse |
| Food/Dietary | No significant food interactions. Food does not affect absorption of oral tablets or ODT. Nasal spray should be used without regard to meals. Avoid alcohol during migraine attacks as it may worsen symptoms. |
Loading safety data…
| L2 (Probably Compatible) |
| Teratogenic Risk | Pregnancy Category D. First trimester: limited human data; animal studies show embryotoxicity and teratogenicity (cardiovascular and skeletal anomalies) at maternal toxic doses. Second and third trimesters: risk of premature uterine contractions and potential fetal hypoxia due to vasoconstriction. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for signs of ischemia or hypertensive crisis. In pregnancy, monitor fetal heart rate and uterine activity during administration. Assess for signs of serotonin syndrome if co-administered with serotonergic drugs. |
| Fertility Effects | No human data on fertility effects. Animal studies show no significant impairment of fertility at subtoxic doses. Potential for reduced conception due to vasoconstrictive effects on uterine blood flow. |
| Clinical Pearls | ZOMIG (zolmitriptan) is a serotonin 5-HT1B/1D receptor agonist used for acute migraine treatment. It is available as a tablet, orally disintegrating tablet (ODT), and nasal spray. Onset of action is 30-60 minutes; ODT and nasal spray may have faster absorption. Contraindicated in patients with ischemic heart disease, uncontrolled hypertension, hemiplegic or basilar migraine, and within 24 hours of other triptans or ergotamines. Caution in patients with risk factors for coronary artery disease. Do not use prophylactically. Maximum daily dose is 10 mg (oral) or 10 mg (nasal). Renal impairment: reduce dose. |
| Patient Advice | Take ZOMIG at the first sign of a migraine headache. Do not use to prevent migraines. · If symptoms do not improve after the first dose, do not repeat before 2 hours. Do not exceed two doses in 24 hours. · Do not take ZOMIG within 24 hours of another triptan or ergotamine-containing medication. · Report chest pain, shortness of breath, irregular heartbeat, or sudden severe abdominal pain immediately. · Avoid driving or operating machinery until you know how ZOMIG affects you; dizziness or drowsiness may occur. · Do not take more than the recommended dose. Overdose can cause serious heart problems. |