Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute migraine treatment.

Objective: To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine.

Background: Rizatriptan is a selective 5-HT1B/1D agonist approved for the acute treatment of migraine. Acetaminophen has been studied for acute migraine treatment. In consideration of the prominent central and peripheral mechanisms in migraine, the use of "multi-mechanism therapy" is gaining momentum in the treatment of acute migraine attacks.

Study Design: This was a randomized, double-blind, placebo-controlled trial conducted at 10 centers. Eligible patients with migraine according to International Headache Society criteria treated a single migraine attack of moderate or severe intensity within 4 h from pain onset. Patients were randomized into 1 of 4 groups (rizatriptan 10 mg + acetaminophen 1000 mg [RA], rizatriptan alone [R], acetaminophen alone [A], and placebo [P]). There were 3 co-primary hypotheses tested sequentially for 2-h pain relief: (1) RA would be superior to P; (2) if the first was fulfilled, RA would be superior to A; and (3) if the first 2 were fulfilled, RA would be superior to R.

Results: Of 173 patients who treated a migraine, 123 patients (71.5%) achieved pain relief within 2 h. RA (90%) was significantly better than P (46%) and A (70%), but only numerically better than R (77%) for 2-h pain relief. No significant differences were seen between the active treatment groups in adverse events.

Conclusion: Rizatriptan coadministered with acetaminophen achieved 2 of the 3 primary hypotheses, proving superior to both acetaminophen and placebo for 2-h pain relief, but failing to achieve superiority to rizatriptan alone. RA was as well tolerated as each of the individual agents.