Ketorolak

Additional information

The scientific literature indicates that pain behavior and pain perception may vary between men and women. This could be influenced by differences in pharmacokinetics, sex hormones, differences in stress response, or type of pain test. Also, many variables other than a person’s sex/gender account for individual differences in pain sensitivity. The prevalence of several clinical pain conditions is higher in women than in men, which suggests that either different clinical pain mechanisms may operate in men vs. women, or different or additional risk factors are relevant in one sex, or a combination of differences [1-3]. Therefore, sex differences of pain releasing medication might thus be difficult to interpret [4].

Pharmacokinetics and dosing

Ketorolac is primarily eliminated renally (91%) [5]. Pooled data from two pharmacokinetic studies showed that after a single dose of ketorolac (i.v. 0.5 mg/kg), clearance was 37% higher in men than a non-pregnant woman of the same body weight. This sex difference was suggested to be explained by higher renal elimination and higher glucuronidation activity in men. Furthermore, clearance of 20 mg ketorolac administrated to women at the time of delivery were 55% higher than in non-pregnant women with the same body weight [6].

Effects

The analgesic efficacy of ketorolac (10 mg p.o.) was evaluated in a double-blind, placebo-controlled experimental pain method using cold pressor test (25 men, 25 women). No difference between men and women in ketorolac response was found [7].

Adverse effects

 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 levels of circulating hormones and/or more poly-pharmacy in women [8] or to a generally higher risk of drug-induced liver injury in women [9]. If this is an adverse effect for NSAIDs in general or only associated with certain NSAIDs is unclear. If ketorolac was included is not specified.

A meta-analysis evaluated NSAID use and the risk of Parkinson’s disease. Pooled risk ratios 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)) [10]. If this is an effect for NSAIDs in general or only associated with certain NSAIDs is unclear. If ketorolac was included is not specified.

Reproductive health issues

Studies on animal models shows that non-selective NSAIDs (diclofenac, ibuprofen, ketoprofen, ketorolac, naproxen) can affect implantation and ovulation and small clinical studies report that non-selective NSAIDS may cause decreased fertility in some women. However, the effect is reversible after treatment discontinuation [5, 11-14]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).