Combined over-the-counter knee pain analgesics may risk blood loss
MedWire News: Combining acetaminophen and ibuprofen offers a modest improvement in pain relief for chronic knee pain at the cost of a significantly increased impact on hemoglobin blood loss, possibly though gastrointestinal bleeding , UK researchers warn.
The team examined the efficacy and safety of over-the-counter single and combined analgesics in 892 patients, aged an average of 60.6 years, who had radiographic knee osteoarthritis.
The researchers randomly assigned patients to receive three times daily one of four regimes: ibuprofen 400 mg; acetaminophen 1000 mg; or either one or two single fixed dose tablets containing ibuprofen 200 mg and acetaminophen 500 mg.
The patients were assessed after 10 days and 13 weeks of treatment using the Western Ontario McMasters Universities osteoarthritis index (WOMAC) regarding the acceptability of pain in the past 48 hours. The participants also underwent a raft of medical assessments, including for hematology markers and osteoarthritis signs, and all moderate and severe adverse events were reported.
As reported in the Annals of Rheumatology, WOMAC pain scores at day 10 showed that two combination tablets offered significantly superior pain relief to acetaminophen alone and a nonsignificant improvement compared with one combined tablet or ibuprofen alone.
At 13 weeks, patients taking one or two combination tablets were significantly more likely to rate their treatment as excellent or good compared with patients taking acetaminophen alone.
The median incidence of moderate and severe adverse events was the same for the four treatment groups, at 1.1 per person-days exposure, with dyspepsia, diarrhea, and nausea the most commonly reported.
However, patients taking two combination tablets were significantly more likely to have a hemoglobin drop from baseline of at least 1 g/dl than patients in the other treatment groups (38.4% vs 20.3% for acetaminophen, 19.6% for ibuprofen, and 24.1% for one combined tablet).
"Decreases in hemoglobin were accompanied by an increase in mean platelet counts and a reduction in mean red cell volume, suggesting that these hemoglobin decreases may relate to blood loss," say Michael Doherty (City Hospital, Nottingham) and co-workers.
An important novel finding was that, in this population, paracetamol 3 g/day may cause similar degrees of blood loss (predominantly asymptomatic) as ibuprofen 1200 mg/day, and that the combination of the two appears to be additive, or even synergistic in terms of the number of individuals with a greater than 2 g/dl decrease in hemoglobin.
The researchers recommend further research to confirm their novel finding that acetaminophen 3 g/day may result in blood loss comparable to that of ibuprofen 1.2 mg/d, and that the analgesics have an additive or synergistic impact on hemoglobin, possibly through gastrointestinal blood loss.
"If confirmed, this observation should lead to the re-consideration of current recommendations for oral analgesic use in osteoarthritis, and in chronic pain in general, and to the consideration of strategies to reduce this side-effect," Doherty et al conclude.
By Lynda Williams