Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: A 1-Week, randomized, double-blind, placebo-controlled trial

• Published in: Clinical therapeutics 2006-12, Vol.28 (12), p.2052-2060
• Main Authors: Lee, Eun Young, Lee, Eun Bong, Park, Byung Joo, Lee, Chang Keun, Yoo, Bin, Lim, Mi Kyoung, Shim, Seung-Cheol, Sheen, Dong-Hyuk, Seo, Young, Ah Kim, Hyun, Baek, Han Joo, Song, Yeong Wook
• Format: Article
• Language: English
• Subjects: acetaminophen; Acetaminophen - administration & dosage; Acetaminophen - adverse effects; Acetaminophen - therapeutic use; Adult; Aged; Analgesics; Analgesics - administration & dosage; Analgesics - adverse effects; Analgesics - therapeutic use; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Chronic pain; combination therapy; Diseases of the osteoarticular system; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Inflammatory joint diseases; Internal medicine; Male; Medical schools; Medical sciences; Middle Aged; Narcotics; Nonsteroidal anti-inflammatory drugs; Osteoarthritis; pain; Pain - drug therapy; Pain - etiology; Pain management; Pain Measurement; Pharmacology. Drug treatments; Preventive medicine; Recovery of Function; Rheumatoid arthritis; Rheumatology; Tablets; Toxicity; tramadol; Tramadol - administration & dosage; Tramadol - adverse effects; Tramadol - therapeutic use; Treatment Outcome; University colleges
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2006.12.019

This study evaluated the efficacy and tolerability of tramadol 37.5-mg/acetaminophen 325-mg combination tablets (tramadoUAPAP) as add-on therapy in subjects with rheumatoid arthritis (RA) pain that was inadequately controlled by NSAIDs and disease-modifying antirheumatic drugs alone. Subjects in this multicenter, double-blind trial were randomized in a 3:1 ratio to receive 1 tramadol/ APAP tablet TID or a matching placebo for 1 week. Stable doses of previous medications were continued during the study. The primary efficacy variable was the mean daily pain relief score over 1 week, measured on a 6-point scale (4 = complete; ' = a lot; 2 = some; 1 = a little; 0 = none; -1 = worse). Secondary outcomes included the mean daily pain intensity score, measured on a 100-mm visual analog scale (VAS) (from 0 mm = no pain to 100 mm = extreme pain); pain intensity and pain relief at day 7; subjects' and investigators' mean overall assessments of study drug, measured on a Likert scale (from 2 = very good to -2 = very poor); and subjects' assessments of 8 aspects of physical function (measured on the Health Assessment Questionnaire). Of 277 subjects randomized to treatment, 267 (201 tramadol/APAP, 66 placebo) were included in the intent-to-treat population. Mean (SD) daily pain relief scores at the end of 1 week were significantly greater in the tramadol/APAP group compared with the placebo group (1.04 [0.89] vs 0.78 [0.80], respectively; P = 0.037), and mean daily pain intensity scores at the end of 1 week were significantly lower (47.23 [19.96] vs 53.81 [16.59]; P = 0.018). Physical function at the end of 1 week did not differ significantly between tramadol/APAP and placebo. Two hundred seventy-two subjects (205 tramadol/APAP, 67 placebo) were evaluable for tolerability. One hundred thirty-three of these subjects had at least 1 adverse event. The incidence of adverse events was significantly higher in the tramadol/APAP group than in the placebo group (57.6% vs 22.4%; P < 0.001). Discontinuations due to adverse events occurred in 19.0% of the tramadol/APAP group and 3.0% of the placebo group ( P = 0.001). Of 213 treatment-related adverse events in tramadol/APAP subjects, nausea (34.1%) was the most frequent, followed by dizziness (20.0%) and vomiting (15.6%). One serious adverse eventchest discomfort, nausea, and vomiting after taking study medication—occurred in a subject receiving tramadol/APAP The symptoms resolved 1 day after discontinuing tramadol/APAP In this stud