Triptans

Triptans are selective 5HT1B and 5HT1D agonists that constrict cranial vessels and block release of CGRP and other peptides from trigeminal nerve endings. They are the most effective specific drugs for acute migraine and cluster headache.

Pharmacokinetics. Oral bioavailability is low for sumatriptan (14 percent) and higher for rizatriptan and eletriptan. Subcutaneous sumatriptan acts in 10 minutes; oral triptans act in 30 to 60 minutes.

• Sumatriptan 50 to 100 mg orally; maximum 300 mg daily; 6 mg subcutaneously, repeated after 1 hour, maximum 12 mg daily; nasal 10 to 20 mg, maximum 40 mg daily.
• Rizatriptan 10 mg orally; 5 mg with propranolol; maximum 30 mg daily (15 mg with propranolol).
• Zolmitriptan 2.5 to 5 mg orally; maximum 10 mg daily.
• Naratriptan 2.5 mg orally; maximum 5 mg daily.
• Eletriptan 40 mg orally; maximum 80 mg daily.
• Almotriptan 12.5 mg orally; maximum 25 mg daily.
• Frovatriptan 2.5 mg orally; maximum 7.5 mg daily.

Differences. Eletriptan, rizatriptan and zolmitriptan act fastest. Naratriptan and frovatriptan act slowly with less recurrence and fewer adverse effects. Subcutaneous or nasal routes suit vomiting.

• Timing: take once the headache starts, while pain is mild; not during aura alone.
• Repeat dosing: for oral triptans, repeat after 2 hours if the headache returns after relief; do not repeat if the first dose gave no relief for that attack.
• Combination: with naproxen 500 mg or an antiemetic improves response.
• Failure: try a different triptan or route over 3 attacks.
• Cluster headache: sumatriptan 6 mg subcutaneously (maximum 12 mg daily) or oxygen 12 to 15 L/min for 15 minutes.
• Limits: use on fewer than 10 days a month.

Selection. Assess cardiovascular risk before the first dose in men over 40, postmenopausal women and those with risk factors; give the first dose under supervision if risk is uncertain.

Contraindications. Ischaemic heart disease, previous myocardial infarction, coronary vasospasm, stroke or transient ischaemic attack, uncontrolled hypertension, peripheral vascular disease, hemiplegic or basilar migraine, severe liver impairment, and ergot use within 24 hours. MAO inhibitors within 2 weeks (sumatriptan, rizatriptan). Eletriptan with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir-boosted antiretrovirals).

Adverse effects. Tingling, flushing, dizziness, fatigue, chest, throat and neck tightness (usually non-cardiac), rarely coronary spasm, myocardial infarction, stroke and mesenteric ischaemia. Serotonin syndrome is rare with SSRIs.

Interactions. Propranolol raises rizatriptan levels. Ergots and other triptans add vasoconstriction. Serotonergic drugs add risk.

Special groups.

• Pregnancy: sumatriptan acceptable when needed.
• Breastfeeding: sumatriptan acceptable.
• Children: adolescents from 12 years, sumatriptan nasal 10 to 20 mg or zolmitriptan nasal 5 mg where licensed.
• Older adults: avoid.
• Kidney impairment: no adjustment for most.
• Liver impairment: lower doses; avoid in severe impairment.

Monitoring. Frequency of use, blood pressure, and symptoms of ischaemia.

Referral and escalation. Chest pain after a dose needs emergency assessment. Use on 10 or more days a month, or failure of 2 triptans, needs specialist review.