Drug products: Alpoxen, Bonyl, Eox, Ipaflex, Miranax, Naprocur, Naprosyn, Naprosyn®, Naprosyn® Entero, Naproxen 2care4, Naproxen ABECE, Naproxen Apofri, Naproxen Bluefish, Naproxen Ebb, Naproxen Mylan, Naproxen Orifarm, Pronaxen, Pronaxen®, Vimovo
ATC code: M01AE02, M01AE52
Substances: naproxen, naproxen sodium
Published controlled studies on differences between men and women regarding the efficacy of naproxen are lacking. Studies have found women to have a higher free concentration if naproxen but the clinical significance of this is unclear.
A large retrospective study shows a higher risk of gastric bleedings in all NSAID-treated patients, with a higher risk elevation in men.
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.
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.
Plasma samples from patients (62 men, 173 women) with osteoarthritis treated with 750 mg naproxen, showed that women had 65% higher free concentration and 41% higher unbound fraction than men. However, no association between free concentration and effect or adverse events was found within the naproxen concentration ranges in this study . Another larger study found similar results (192 men, 433 women) . No sex differentiation in dosing has been recommended by the manufacturer .
No studies with a clinically relevant sex analysis regarding the effects of naproxen have been found.
A nested control study 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 diclofenac was 2.2 compared to 4.0 for naproxen, and 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