acetaminophen
Place in Therapy
Acetaminophen (up to 4 grams/day) is considered an effective initial oral pharmacologic therapy for the treatment of symptomatic mild-to-moderate pain due to hip or knee osteoarthritis (OA), and is considered first line non-prescription pharmacological agent for the treatment of OA pain1,2,3. Because of acetaminophen’s relatively benign safety profile in a range of patient populations (for example, from adults of 18+ years to the elderly 65+ years), acetaminophen is also the preferred agent for long-term analgesic therapy of mild-to-moderate osteoarthritis1,2. Of note, some clinicians also consider acetaminophen to be especially efficacious in the treatment of chronic, non-inflammatory mechanical knee pain4.
Despite acetaminophen’s first line place in therapy1,2,3, the efficacy of acetaminophen has been questioned when compared to non-steroidal anti-inflammatory drugs (NSAIDs)1,5,6. Although NSAIDs are considered to have superior efficacy over acetaminophen for treatment of OA pain1,5,6, the difference in effect is modest5. Short-term studies showed no difference in adverse effects of acetaminophen versus NSAIDs; however, average duration of study was no longer than 6 weeks5, and although the differences were not significant, studies showed that patients receiving NSAIDs tended to have more GI adverse effects than acetaminophen5,7. It is well-established that NSAIDs carry considerable GI and other adverse risks despite the superiority of NSAIDs over acetaminophen in controlling pain in OA1,2.
Thus, the decision to choose acetaminophen over NSAID therapy in a patient with mild-to-moderate OA is largely patient specific, where several factors must be considered prior to initiation of therapy5. Namely, age (e.g. ≥ 65), co-morbidities (e.g. congestive heart failure, renal impairment, hepatic impairment, history of gastric ulcers, alcoholism), the site and characteristics of OA pain, current medication use (e.g. anticoagulants/ASA, oral glucocorticoids, multiple and/or high-dose NSAID use, alcohol consumption), past medication use, product availability/dosage form, patient preference, and cost1,5 should all be considered when weighing the risks versus benefits of initiating acetaminophen therapy over NSAIDs for the purposes of OA-related pain relief.
In choosing acetaminophen for OA pain, acetaminophen should be dosed as 650 mg q4H or 1000 mg q6h, to a maximum of 4 grams in 24 hours1,2. Patients must be counseled to never exceed 4 grams daily in TOTAL acetaminophen intake from all sources (Rx, OTC) in order to avoid potential acetaminophen toxicity1,2. A 2 to 3 week trial of acetaminophen use (never exceeding 4 g/day) is the recommended appropriate timeframe to assess for efficacy of pain relief in OA1.
References:
1. E-therapeutics. Musculoskeletal Disorders:Osteoarthritis. 2012. Accessed March 14, 2014 at https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0059
2. Grinrod K & Marra C. Patient Self Care Chapter 48: Osteoarthritis. In: Patient Self Care: 2nd Edition. Canadian Pharmacists Association. pp 456-470.
3. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American college of Rheumatology Subcomittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000. 43(9): 1905-15.
4. Miceli-Richard C, Le Bars M, Schmidely N et al. Paracetamol in osteoarthritis of the knee. Ann Rheum Dis. 2004. 63(8): 923-30.
5. Towheed T, Maxwell L, Judd M et al. Acetaminophen for osteoarthritis (Review). Cochrane Database of Systematic Reviews. 2006; (1): CD004257.
6. Boureau F, Schneid H, Zeghari N et al. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomized comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip. Ann Rheum Dis. 2004; 63(9): 1028-1034.
Lee C, Straus WL, Balshaw R et al. A comparison of the efficacy and safety of nonsteroidal anti-inflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum. 2004. 51(5): 746-54.
Despite acetaminophen’s first line place in therapy1,2,3, the efficacy of acetaminophen has been questioned when compared to non-steroidal anti-inflammatory drugs (NSAIDs)1,5,6. Although NSAIDs are considered to have superior efficacy over acetaminophen for treatment of OA pain1,5,6, the difference in effect is modest5. Short-term studies showed no difference in adverse effects of acetaminophen versus NSAIDs; however, average duration of study was no longer than 6 weeks5, and although the differences were not significant, studies showed that patients receiving NSAIDs tended to have more GI adverse effects than acetaminophen5,7. It is well-established that NSAIDs carry considerable GI and other adverse risks despite the superiority of NSAIDs over acetaminophen in controlling pain in OA1,2.
Thus, the decision to choose acetaminophen over NSAID therapy in a patient with mild-to-moderate OA is largely patient specific, where several factors must be considered prior to initiation of therapy5. Namely, age (e.g. ≥ 65), co-morbidities (e.g. congestive heart failure, renal impairment, hepatic impairment, history of gastric ulcers, alcoholism), the site and characteristics of OA pain, current medication use (e.g. anticoagulants/ASA, oral glucocorticoids, multiple and/or high-dose NSAID use, alcohol consumption), past medication use, product availability/dosage form, patient preference, and cost1,5 should all be considered when weighing the risks versus benefits of initiating acetaminophen therapy over NSAIDs for the purposes of OA-related pain relief.
In choosing acetaminophen for OA pain, acetaminophen should be dosed as 650 mg q4H or 1000 mg q6h, to a maximum of 4 grams in 24 hours1,2. Patients must be counseled to never exceed 4 grams daily in TOTAL acetaminophen intake from all sources (Rx, OTC) in order to avoid potential acetaminophen toxicity1,2. A 2 to 3 week trial of acetaminophen use (never exceeding 4 g/day) is the recommended appropriate timeframe to assess for efficacy of pain relief in OA1.
References:
1. E-therapeutics. Musculoskeletal Disorders:Osteoarthritis. 2012. Accessed March 14, 2014 at https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0059
2. Grinrod K & Marra C. Patient Self Care Chapter 48: Osteoarthritis. In: Patient Self Care: 2nd Edition. Canadian Pharmacists Association. pp 456-470.
3. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American college of Rheumatology Subcomittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000. 43(9): 1905-15.
4. Miceli-Richard C, Le Bars M, Schmidely N et al. Paracetamol in osteoarthritis of the knee. Ann Rheum Dis. 2004. 63(8): 923-30.
5. Towheed T, Maxwell L, Judd M et al. Acetaminophen for osteoarthritis (Review). Cochrane Database of Systematic Reviews. 2006; (1): CD004257.
6. Boureau F, Schneid H, Zeghari N et al. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomized comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip. Ann Rheum Dis. 2004; 63(9): 1028-1034.
Lee C, Straus WL, Balshaw R et al. A comparison of the efficacy and safety of nonsteroidal anti-inflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum. 2004. 51(5): 746-54.