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Paracetamol (acetaminophen) for osteoarthritis

 

Clinical bottom line

Four trials confirm clinical judgement, that paracetamol 4,000 mg daily is better than placebo but probably inferior to top daily doses of NSAIDs. About a quarter of patients will discontinue over 4-6 weeks.


SYSTEMATIC REVIEW

This Bandolier review was concluded in June 2002.

The main inclusion criteria were that trials had to be randomised and double blind, to have paracetamol (acetaminophen) at sensible doses of 3,000 mg or 4,000 mg a day (without any other added active agent), have a duration of at least four weeks, have at least 50 patients in the trial, and be in osteoarthritis.

Findings

There were only four trials that fulfilled these inclusion criteria, and the main results are outlined in Table 1. Paracetamol 4000 mg daily was better than placebo in one trial, about the same as ibuprofen, but inferior to diclofenac and rofecoxib at usual daily doses. Total discontinuations in 345 patients over 4-6 weeks were 27%, 8% because of adverse events and 9% because of lack of efficacy.

Table 1: Clinical trials of paracetamol in osteoarthritis

Reference

Design

Included patients

Major exclusions

Treatments

Outcome

Results

Total discontinuations

Geba et al. JAMA 2002 287: 64-71 Randomised, double-blind parallel group comparison with rofecoxib and celecoxib for 6 weeks Symptomatic OA knee for six months, minimum VAS of 40 mm while off drug Concurrent medical or arthritic disease with potential to confound or interfere, hypersensitivity Paracetamol 4000 mg (n=94)
Rofecoxib 12.5 mg (n=96)
Rofecoxib 25 mg (n=95)
Celecoxib 200 mg (n=97)
Pain on walking, pain at rest, at night, morning stiffness, global response Both rofecoxib doses significantly better than paracetamol (good, excellent response on patient global assessment). Paracetamol 4000 mg (29/94)
Rofecoxib 12.5 mg (17/96)
Rofecoxib 25 mg (18/95)
Celecoxib 200 mg (17/97)
Pincus et al. Arth Rheum 2001 44: 1587-1598 Randomised, double-blind crossover comparison with diclofenac + misoprostol for 6 weeks each period Symptomatic OA of hip or knee, age over 40 years, VAS score of 30 mm or more Severe comorbidity, hypersensitivity Paracetamol 4000 mg (n=115)
Diclofenac 150 mg plus misoprostol 400 µg (n=112)
Pain on walking, pain at rest, at night, morning stiffness, and others Diclofenac had more efficacy, but more adverse effects than paracetamol Paracetamol 4000 mg (33/115)
Diclofenac 150 mg (40/112)
Bradley et al. NEJM 1991 325: 87-91 Randomised, double-blind parallel group comparison with ibuprofen for 4 weeks OA knee with pain for at least three months, over 30 years History of surgery, intraarticular corticosteroids, RA Paracetamol 4000 mg (n=60)
Ibuprofen 1200 mg (n=61)
Ibuprofen 2400 mg (n=61)
Tenderness, swelling, time for 50 foot walk No difference between treatments Paracetamol 4000 mg (16/61)
Ibuprofen 1200 mg (12/62)
Ibuprofen 2400 mg (12/61)
Kjaersgaard-Andersen et al. Pain 1990 43: 309-318 Randomised double-blind comparison of paracetamol with paracetamol and codeine over 4 weeks Clinical and radiographic evidence of OA hip with chronic pain Significant impairment of lungs, liver or kidneys, or peptic ulcer history Paracetamol 3000 mg (n=75)
Paracetamol 3000 mg plus codeine 60 mg (n=83)
Pain and adverse events Trial discontinued early because of adverse events Paracetamol 3000 mg (17/75)
Paracetamol 3000 mg plus codeine 60 mg (43/83)

 

Comment

Based on this paucity of information it is hard to draw any sensible conclusions, other than such trials as we have broadly confirm clinical judgement, that paracetamol 4,000 mg daily is effective for some patients, but will generally be inferior to top doses of NSAIDs.