Level 2: Mid-level evidence
Both sumatriptan (Imitrex) and naproxen sodium (Aleve, others) are used to treat a migraine attack. A new but not yet commercially available combination tablet containing sumatriptan 85 mg plus naproxen sodium 500 mg was compared with sumatriptan monotherapy and naproxen sodium monotherapy in two placebo-controlled randomized trials funded by Bayer, the manufacturer of Aleve (JAMA. 2007;297: 1443-1454).
Both trials used the same methodology at 118 clinical centers in the United States. Men and nonpregnant, nonlactating women aged 18-65 years with a history of two to six migraines per month were randomized to one of four tablets to be used once after onset of moderate-to-severe pain: (1) fixed-dose sumatriptan 85 mg plus naproxen sodium 500 mg, (2) sumatriptan 85 mg, (3) naproxen sodium 500 mg, or (4) placebo.
Patients were allowed to use rescue medication two hours after dosing, but a second dose of study medication was not allowed. Primary efficacy analysis included patients who took study medication, recorded baseline pain as moderate or severe, and had at least one post-baseline efficacy evaluation. Safety analysis included all patients who took the study medication.
There were 1,677 patients enrolled in the first trial; 1,441 patients (86%) were included in efficacy analysis and 1,461 (87%) included in safety analysis. Comparing combination vs. sumatriptan vs. naproxen sodium vs. placebo at two hours and again at 2-24 hours, patients taking the combination tablet reported the most pain relief and the least nausea, photophobia, and phonophobia. In addition, patients taking the combination required less rescue medication and had less recurrence at 2-24 hours than the other three groups. The NNT to achieve the positive results with the combination tablet ranged from 3 to 15. Results in the second trial of 1,736 patients were generally similar.
Combination therapy caused more side effects, however. In the first trial, 27% vs. 24% vs. 13% vs. 12% of patients had any adverse event (NNH 6 for combination vs. placebo, NNH 7 for combination vs. naproxen); 20% vs. 19% vs. 8% vs. 8% had any related adverse event (NNH 8 for combination vs. placebo, NNH 8 for combination vs. naproxen). No specific adverse event accounted for >3% absolute difference in rates.
In the second trial, 26% vs. 28% vs. 14% vs. 10% of patients had any adverse event (NNH 6 for combination vs. placebo, NNH 8 for combination vs. naproxen); 22% vs. 25% vs. 10% vs. 9% had any related adverse event (NNH 8 for combination vs. placebo, NNH 8 for combination vs. naproxen). No specific adverse event accounted for >3% absolute difference in rates.Since the combination tablet (Trexima) is not yet available, 1.5 tablets of 50 mg sumatriptan plus naproxen might be effective in replicating the results.