Zolmitriptan
Zolmitriptan
Generic Name
Zolmitriptan
Mechanism
- Selective agonist at 5‑HT₁B/1D receptors located on cranial blood vessels and trigeminal pain pathways.
- Triggers vasoconstriction of dilated cranial arteries → ↓ neurogenic inflammation.
- Inhibits neuropeptide release (CGRP, substance P) from trigeminal afferents → ↓ pain signaling.
- Induces centrally mediated anti‑nausea via limbic system modulation.
Pharmacokinetics
| Parameter | Typical Value | |
| Formulation | Oral tablet (5 mg/10 mg), sub‑lingual 4 mg, oral dissolving 2 mg | |
| Absorption | Rapid; peak plasma concentration (T_max) ×~1 h (oral), ~0.8 h (SL) | |
| Bioavailability | 50‑60 % (oral), ~70 % (SL) | |
| Half‑life | 3–4 h (oral); 2.7‑3.5 h (SL) | |
| Metabolism | Primarily hepatic (CYP1A2, CYP2C19); *minor* CYP3A4 involvement | |
| Excretion | Renal (30–50 %) and fecal (30‑40 %) | |
| Food Effect | High‑fat meal may delay Tmax (~30 min) and slightly reduce C_max (~12 %) |
Indications
- Abortive treatment of migraine with or without aura in adults.
- Pain‑free or intermediate response to single dose in patients with mild to moderate migraine severity.
Contraindications
| Contraindicated in | Key Warnings |
| History of cardiovascular disease (unstable angina, MI, stroke, uncontrolled hypertension) | Caution in mild to moderate CAD; avoid if >3 episodes/month. |
| Severe hepatic impairment | Reduced clearance; dose adaptation not established. |
| Severe renal impairment | Cumulative exposure may increase; monitor. |
| Pregnancy (due to limited data) | Use only if benefits outweigh risks; consider alternatives. |
| Known hypersensitivity to zolmitriptan or excipients | Discontinue immediately. |
| Concurrent use of MAOIs or other serotonergic agents | Significantly ↑ risk of serotonin syndrome. |
Dosing
- Oral tablets: 5 mg → 10 mg after 2 h *if symptoms persist*.
- Sub‑lingual 4 mg (available in select markets) offers quicker onset.
- Oral dissolving 2 mg (for rapid onset in patients who cannot swallow).
- Maximum: 20 mg/day (e.g., 10 mg twice) or 10 mg twice/day, whichever is lower.
- Missed dose: If pain persists beyond 2 h, a second dose may be taken; avoid repeated doses until 24 h have elapsed.
Monitoring
- Vital signs: BP, HR at baseline and 2–3 h post‑dose if cardiovascular risk.
- Cardiac assessment: ECG in patients with known CAD or use of concomitant vasoconstrictors.
- Liver enzymes: Baseline AST/ALT if chronic hepatic disease anticipated.
- Renal function: Creatinine clearance if kidney impairment suspected.
- Patient diary: Document frequency, dosage, and symptom relief for dose optimization.
Clinical Pearls
- *Rapid Onset Advantage*: The sub‑lingual and dissolving formulations avoid first‑pass metabolism, providing an earlier onset (≈20‑30 min) – useful for patients who cannot swallow or require urgent relief.
- *Dose Escalation Strategy*: If a 5 mg dose fails, a 10 mg dose is the most common escalation; avoid exceeding 20 mg/day to stay within safety margins.
- *Cardio‑Safety Profile*: Zolmitriptan has a moderate vasoconstrictive effect; patients with stable angina may tolerate it, but those with uncontrolled hypertension or recent MI should use caution.
- *Serotonin Syndrome Precaution*: Avoid combination with SSRIs, SNRIs, or tramadol. If accidental overlap occurs, discontinue immediately and monitor for agitation, tremor, hyperreflexia.
- *Missed Dose Tip*: Resist the urge to take a second dose before 2 h; this can increase risk of vasospasm and serotonin syndrome.
- *Pregnancy Use*: While data are scarce, no teratogenic effects have been reported; however, clinicians usually recommend avoidance unless migraine causes significant morbidity.
- *Combination Therapy*: Zolmitriptan can be safely combined with NSAIDs (e.g., naproxen) for additive benefit; avoid combining with ergot derivatives.
--
• Key Keywords: *Zolmitriptan, migraine, 5‑HT₁B/1D agonist, rapid onset, sub‑lingual, contraindications, cardiovascular, serotonin syndrome, dosing strategy*
---