Acetaminophen 1,000mg Provides Incremental Benefit Over Acetaminophen 650mg

HONOLULU, HI — Acetaminophen 1,000mg does provide an incremental benefit vs. acetaminophen 650mg, reported Daniel Qi, from McNeil Consumer Healthcare, Fort Washington, PA, at the American Pain Society's 31st Annual Scientific Meeting.

Dr. Qi and his colleagues utilized the Dental Impaction Pain Model to evaluate the dose-response relationship of acetaminophen 1,000mg vs. 650mg over 6 hours. This randomized, double-blind, parallel-group, placebo-controlled study enrolled 540 patients (52% female, aged 16–50 years, 95% Caucasian) who required surgical removal of impacted third molars. Patients were given a single dose of acetaminophen 1,000mg, acetaminophen 650mg, or placebo when moderate or greater pain and a Visual Analog Scale (VAS) score >50 out of 100mm was reported within four hours following surgery. Patients were encouraged to wait at least 90 minutes prior to rescuing.

Pain intensity and pain relief were measured over six hours at 15, 30, 45, 60, 75, and 90 minutes, and at 2, 3, 4, 5, and 6 hours (VAS 0–100mm) to assess the primary efficacy endpoint of the weighted Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) scores over six hours (SPID6). Acetaminophen 1,000mg showed a 24% improvement in VAS score compared to 650mg (529.4 vs. 427.3; P=0.001). Acetaminophen 1,000mg was also significantly superior to 650mg in the following categories: SPID6 (P=0.001), TOTPAR6 (P=0.002),Time to Rescue Analgesic (P<0.001), rescue rates through four hours (20% vs. 32%; P=0.002)) and six hours (29% vs. 46%; P<0.001). The Subject Global Evaluation also showed more “very good” or “excellent” ratings for the acetaminophen 1,000mg than the 650mg (49% vs. 35%; P=0.001).

Compared to placebo, both dosages of acetaminophen were significantly superior (P<0.001) in achieving the efficacy endpoints. Both active treatment groups demonstrated similar stopwatch Times to Confirmed First Perceptible and Meaningful Relief. Adverse events were reported by 18.5% of subjects, with no clinically important difference among the three treatment groups. No serious adverse events were reported and no subjects discontinued due to an adverse event.

In response to the recent FDA Advisory Committee Meeting questioning the benefit of the two strengths of acetaminophen, Dr. Qi stated, “This study provides definitive evidence of a positive and clinically relevant dose-response between acetaminophen 650mg and acetaminophen 1,000mg.”