Drug products: Ketoflex, Ketoprofen Mylan, Ketospray, Orudis®, Orudis® Retard, Profenid, Siduro®, Siduro® Retard, Zon
ATC code: M01AE03, M02AA10
The risk of NSAID-induced liver affection was in a small case-control study larger in women, but a large cohort study did not find any differences in risk between men and women.
A large retrospective study found a higher risk of gastric bleeding in patients treated with NSAID and the risk was higher in men. Another study on patients with rheumatoid arthritis and ketoprofen treatment found a higher risk of gastric bleeding in women.
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.
The pharmacokinetics of ketoprofen enantiomers were evaluated in healthy volunteers (12 men, 13 women) in an unblinded, randomized crossover study. Doses of 25, 50, or 100 mg of (R)-ketoprofen and 100 mg of racemic ketoprofen (R+S) (Orudis®) were administered orally on four separate occasions at least a week apart. Fractional inversion of (R)-ketoprofen was not different between men and women. Women had a higher elimination rate constant for (R)-ketoprofen after the racemate dose. Clearance did not differ between men and women. Thus, the clinical significance is unclear . No sex differentiation in dosing has been recommended by the manufacturer .
The only study found regarding sex differences in the effect of ketoprofen was a small double-blind placebo-controlled clinical study (6 men, 11 women) on pain and inflammation in osteoarthritis. No differences between men and women were reported .
The safety of ketoprofen was evaluated in a French multicenter study including patients suffering from painful rheumatic disorders and aged over 60 years (6748 men, 13029 women). Patients received 200 mg ketoprofen once daily for one month. A multivariate analysis showed that women had more adverse side effects, especially those related to the gastro-intestinal (GI) tract (men: 15.2%; women: 18.4%). However, the sex of the patient was not prognostic for GI adverse drug reactions . This is contrary to the findings in a large nested control study, which estimated the risk of upper gastrointestinal complications associated with selective cox 2-inhibitors and non-selective NSAIDs compared with non-use of NSAIDs. In all > 600 000 individuals contributed to >1 million person-years of observation and 726 upper gastrointestinal complications were identified. Male sex and high age carried a higher risk of complication and suggested a synergistic effect between these factors and NSAIDs on the risk of upper gastrointestinal complications. The risk for upper gastrointestinal complications differed between the various NSAIDs. Adjusted for male sex and age, the OR for various NSAIDs including ketoprofen was 3.4, compared to 2.2 for diclofenac, 4.0 for naproxen, 1.6 for ibuprofen .A retrospective cohort study (625 307 patients with 2 130 820 prescriptions, one third of these were to men) found that incidence rates of NSAID-induced acute liver injury were similar for men and women and for the young and the elderly . However, a case-control study (136 men, 130 women) found an association between NSAID exposure and liver injury in women but not in men (OR 6.49 vs. 1.06). This may be due to differences in pharmacokinetics or circulating level hormones and/or greater use of multiple medications in women  or to a generally higher risk of drug-induced liver injury in women .A meta-analysis evaluated NSAID use and the risk of Parkinson’s disease. Pooled risk ratio of Parkinson’s disease were similar in men and women using NSAID (men 0.79 (95%CI 0.69, 0.92); women 0.72 (95%CI 0.45, 1.15)) .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2014-10-14
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson