Pharmacokinetic linearity of naproxen and efficacy of naproxen sodium at various doses
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OBJECTIVE: Naproxen sodium (NAPSO) is commonly used in a variety of pain conditions. There are several strengths of NAPSO available over the counter (OTC). Most published data are based on single or multiple doses using 220 mg, hence there is a need to assess the analgesic efficacy of other strengths of NAPSO used in the OTC setting. MATERIALS AND METHODS: We reviewed published and unpublished studies of naproxen (NAP) and NAPSO to establish the pharmacokinetic relationship between dosage, plasma concentration, and efficacy, and to compare the analgesic efficacy of NAPSO 220, 440, and 550 mg or NAP 500 mg versus placebo and active comparators. RESULTS: Increasing OTC doses of NAP are associated with linear pharmacokinetics, i.e., plasma levels of NAP increase proportionately with dosage. Accordingly, the therapeutic efficacy of higher doses of NAP or NAPSO is greater than lower doses. All OTC doses of NAP and NAPSO are significantly more effective than placebo. Higher strengths are as effective or more effective than lower strengths, and at least comparable to other active treatments. CONCLUSION: The pharmacokinetic linearity associated with NAP means that data on efficacy for the lower OTC doses of NAPSO can be extrapolated to the higher OTC doses. Thus, it is given that NAPSO 275 and 550 mg will be at least as effective as or superior to the lower doses of 220 and 440 mg.

Efficacy and safety of naproxen sodium 440 mg versus acetaminophen 600 mg/codeine phosphate 60 mg in the treatment of postoperative dental pain.

PURPOSE: Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with postoperative dental pain. METHODS: The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 2:2:1 ratio, respectively: NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours, time to onset of relief, time to rescue medication and global rating of medication were also assessed. RESULTS: In Study 1, there were 225 subjects evaluated for efficacy, and 228 evaluated for safety. In Study 2, there were 230 subjects evaluated for efficacy and safety. In both studies, NS and AC were significantly better than placebo for almost all efficacy measures. In Study 1, NS was significantly superior to AC for all summed efficacy scores over 4 and 8 hours except for SPID4. NS was also superior to AC for most individual time point scores from 3 through 8 hours, as well as for the time to taking rescue medication. Both actives had a similar onset of effect. The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO. The most frequently reported AEs with AC were gastrointestinal (GI) and nervous system events. In Study 2, there were no statistically significant differences between the two active treatments for any summed efficacy score, except for TOTPAR8, where NS was significantly better than AC. NS was significantly better than AC for individual pain relief time point scores from 3 through 8 hours and significantly better for individual pain intensity difference scores from 5 through 8 hours. AC had a significantly faster onset of effect compared to NS, but NS had a significantly longer time to rescue compared to AC. Nervous system AEs (dizziness and somnolence) were reported significantly more frequently with AC compared to NS. In conclusion, Both NS and AC are effective in the relief of postoperative dental pain. NS provided comparable to superior relief vs. AC and its analgesic effects lasted significantly longer. NS was well tolerated and resulted in a lower rate of AEs than AC. CLINICAL SIGNIFICANCE: In 2017, the US Department of Human Health Services declared a public health emergency to address the national opioid crisis. Since dentists are among the most common specialty groups prescribing opioids, these studies show that NSAIDs (such as naproxen sodium) are effective analgesics for relieving postoperative pain.