ZOLMITRIPTAN
Clinical safety rating: avoid
Contraindicated (not allowed)
Selective serotonin 5-HT1B/1D receptor agonist; causes vasoconstriction of intracranial blood vessels and inhibits trigeminal nerve transmission.
| Metabolism | Hepatic via CYP1A2, with metabolites N-desmethylzolmitriptan (active) and N-oxide and indoleacetic acid derivatives. |
| Excretion | Zolmitriptan is eliminated primarily via hepatic metabolism, with approximately 60% excreted in urine (8-10% as unchanged drug, the remainder as indoleacetic acid and N-oxide metabolites) and 30% in feces. Biliary excretion is negligible. |
| Half-life | Terminal elimination half-life is approximately 3 hours (range 2.5-4.5 hours) for oral and intranasal routes. This short half-life is consistent with the need for acute migraine treatment and supports the possibility of recurrence within 24 hours. |
| Protein binding | Approximately 25% bound to plasma proteins (mainly albumin), which is low and not clinically significant. |
| Volume of Distribution | Volume of distribution is approximately 2.4 L/kg (range 1.8-3.0 L/kg), indicating extensive tissue distribution including penetration across the blood-brain barrier. |
| Bioavailability | Oral bioavailability is 40-48% (first-pass metabolism); intranasal: approximately 40% (similar to oral); orally disintegrating tablet: equivalent to oral tablet. |
| Onset of Action | Oral: onset of effect occurs within 30-60 minutes; intranasal: within 15-30 minutes; orally disintegrating tablet: similar to oral. |
| Duration of Action | Duration of action is 2-4 hours for headache relief, but migraine recurrence within 24 hours is common (up to 30-40%) due to the short half-life. |
2.5 mg or 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 or 3 mg subcutaneous injection (single dose).
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required for mild to moderate renal impairment (CrCl >15 mL/min). For severe renal impairment (CrCl ≤15 mL/min), use is contraindicated due to lack of data. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). For moderate impairment (Child-Pugh B), maximum dose 5 mg in 24 hours. No adjustment needed for mild impairment (Child-Pugh A). |
| Pediatric use | Adolescents ≥12 years: 2.5 mg or 5 mg orally at onset, may repeat after 2 hours, maximum 10 mg in 24 hours. Nasal spray: 5 mg single dose. Safety and efficacy not established in children <12 years. |
| Geriatric use | Not recommended in elderly patients due to increased risk of coronary artery disease and decreased hepatic function; use only if clearly indicated with careful monitoring. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other 5-HT1 agonists and MAOIs can have additive effects Contraindicated in ischemic heart disease and uncontrolled hypertension.
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 0.5. Relative infant dose estimated 3-4% of maternal weight-adjusted dose. Caution recommended; monitor infant for irritability, drowsiness, or feeding difficulties. |
| Teratogenic Risk | Limited human data; animal studies show no evidence of teratogenicity. In first trimester, risk cannot be ruled out. Second and third trimesters: No known fetal risks; however, uterine vasoconstriction may theoretically reduce placental perfusion. |
■ FDA Black Box Warning
Do not use within 24 hours of any triptan or ergotamine-containing medication due to risk of additive vasospastic reactions.
| Common Effects | Dizziness |
| Serious Effects |
History of ischemic heart disease, coronary artery vasospasm, cerebrovascular disease, peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, MAOI use within 14 days.
| Precautions | Risk of myocardial ischemia, arrhythmias, and cerebrovascular events; avoid in patients with uncontrolled hypertension; serotonin syndrome possible with SSRIs/SNRIs. |
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| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate during administration. In late pregnancy, monitor fetal heart rate and uterine activity due to potential vasoconstrictive effects. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies at high doses showed reduced fertility; clinical significance unknown. |