Codeine/acetaminophen and hydrocodone/acetaminophen combination tablets for the management of chronic cancer pain in adults: A 23-day, prospective, double-blind, randomized, parallel-group study

Abstract Background: Analgesics are an essential component of the treatment of cancer-associated pain. Pharmacologic treatment is usually begun with nonopioid analgesics, most frequently acetaminophen. If pain relief is not achieved, the so-called “weak” opioids, such as codeine and hydrocodone, may be used in combination with acetaminophen. Adverse effects (AEs) of the opioids include constipation, somnolence, nausea, and vomiting. Based on the results of a literature search, data comparing the effects of the opioids are lacking. Objective: The purpose of this study was to compare the analgesic efficacy and tolerability of codeine phosphate versus hydrocodone bitartrate in combination with acetaminophen in the relief of cancer-related pain. Methods: This 23-day, prospective, double-blind, randomized, parallel-group study was conducted at 3 Colombian centers: University Libre, Social Security Institute, and General Hospital of Medellín, Cali, Colombia. Outpatients with cancer were eligible for the study if they were aged >-18 years and had chronic (duration, ≥ 3 months) moderate to severe cancer-related pain (score on 10-cm visual analog scale [VAS], > 3 cm [moderate]; score on a 4-point verbal pain-intensity scale, > 1 [moderate]). Eligible patients were randomly assigned to receive 1 tablet of codeine/acetaminophen (C/A) 30/500 mg or hydrocodone/acetaminophen (H/A) 5/500 mg PO q4h (total daily doses, 150/2500 and 25/2500 mg, respectively) for 23 days. In both groups, if pain intensity was rated as > 3 on the VAS at week 1 or 2, the dosage was doubled. The primary end point was the proportion of patients who achieved pain relief (defined as a score of > 1 on a 5-point verbal rating scale [VRS] (0 = none; 1 = a little; 2 = some; 3 = a lot; and 4 = complete) on study days 1 and 2 and weeks 1, 2, and 3. The secondary end point was the proportion of patients in whom pain was decreased (VAS score,