Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain

Objective: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combinatio n codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. Background: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved f ixed-dose combination analgesic containing an opioid and ibuprofen. Methods: In this randomized, parallel-group, double-blind, repeated-dose, a ctive-comparator, 4-week, multicenter study, 469 patients were randomly ass igned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combina tion hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Ef ficacy was measured through pain relief scores, number of daily doses of st udy medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic respo nse, and global assessment scores. Results: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214 ; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%) , other neurologic (21;4.5%), and other unclassified chronic pain (10; 2.1% ). During the 48 hours prior to the study, 351 (74.8%) patients had been tr eated with opioid or opioid-nonopioid combination analgesics. The overall m ean daily pain relief score was significantly greater in the HI2 group (2.2 5 +/- 0.89) than in the HI1 group (1.98 +/- 0.87) (P = 0.003) or the CA gro up (1.85 +/- 0.96) (P < 0.001). The overall mean number of daily doses of s tudy medication was significantly less in the HI2, group (2.94 +/- 0.99) th an in the HI1 group (3.23 +/- 0.76) (P = 0.036) or the CA group (3.26 +/- 0 .75) (P = 0.014). The overall mean number of daily doses of supplemental an algesics was significantly less in the HI2 roup (0.24 +/- 0.49) than in the HI1 group (0.34 +/- 0.58) (P = 0.021) or CA,group (0.49 +/- 0.85) (P = 0.0 10). The number of patients who discontinued treatment due to an unsatisfac tory analgesic response was significantly less in the HI2 group (2; 1.3%) t han in the CA group (12; 7.5%) (P = 0.008), HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA). week 2 (P < 0.001 vs HI1 and CA). and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week I (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA) , and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no signific ant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse even ts in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. How ever, the mean number of pa patients who discontinued treatment due to adve rse events was significantly greater in the HI2 group (40; 26.1%) than in t he HI1 group (23; 14.7%) (P = 0.013). Conclusions: The results of this study suggest that 3-tablet doses of combi nation hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than e ither 1-tablet doses of this combination or 2-tablet doses of combination c odeine 30 mg and acetaminophen 300 mg. Moreover, 2-tablet doses of combinat ion hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.