Acetaminophen
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Dosing and administration[4]
Oral (also IV and rectal forms). Antipyretic analgesic without anti-inflammatory action. Hepatotoxicity is dose-related; account for all acetaminophen-containing products, including combination analgesics.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Pain relief (adjunct) | 325 to 650 mg every 4 to 6 hours, or 1000 mg every 6 to 8 hours. | Maximum 4 g/day in healthy adults; a 3 g/day ceiling is commonly used for added safety, and 2 to 3 g/day or lower in hepatic impairment, chronic alcohol use, low body weight, frailty, or older age. |
Renal adjustment. Generally preferred over NSAIDs in renal impairment; consider extending the dosing interval in severe impairment.
Hepatic. Reduce the maximum dose (2 to 3 g/day or lower) in hepatic impairment or chronic alcohol use, and avoid in severe or active liver disease.
Role in rheumatology is limited: in osteoarthritis it is a conditional, modest-benefit option used mainly when NSAIDs are unsuitable or as a short-term adjunct (ACR and OARSI 2019); in axial spondyloarthritis it is not a disease treatment (NSAIDs address the inflammation) and serves only as adjunctive pain relief.
Monitoring
- No routine monitoring at therapeutic doses.
- Counsel on the daily maximum and on hidden acetaminophen in combination products.
- Overdose is a medical emergency with risk of acute liver failure; manage per acetaminophen poisoning protocols (N-acetylcysteine).
Contraindications
- Severe hepatic impairment or active liver disease.
- Hypersensitivity to acetaminophen.
Key interactions
- Warfarin: regular higher-dose acetaminophen can raise the INR; monitor.
- Chronic alcohol and hepatic enzyme inducers increase hepatotoxicity risk.
Clinical notes
How it is used in arthritis
In osteoarthritis, acetaminophen is a conditionally recommended, modest-benefit option (ACR and OARSI 2019 downgraded it), used mainly for patients who cannot take NSAIDs or as a short-term adjunct. In axial spondyloarthritis it is not part of the treatment recommendations, since it does not address inflammation and NSAIDs are first-line. It is not disease-modifying in any rheumatic disease.[1, 2, 3]
Monitoring
No routine monitoring at therapeutic doses; overdose requires urgent assessment and N-acetylcysteine.[4]
Common effects
Well tolerated at therapeutic doses; hepatotoxicity is the principal dose-related risk.
Important cautions
Lower the daily ceiling in hepatic impairment, chronic alcohol use, malnutrition, low body weight, and frailty; avoid in severe or active liver disease.[4]
References
- Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220-233. doi:10.1002/art.41142 https://doi.org/10.1002/art.41142
- Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27:1578-1589. doi:10.1016/j.joca.2019.06.011 https://doi.org/10.1016/j.joca.2019.06.011
- Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-1613. doi:10.1002/art.41042 https://doi.org/10.1002/art.41042
- Acetaminophen Product Monograph. Health Canada authorized product monograph. https://health-products.canada.ca/dpd-bdpp/