Pregabalin

Additional information

Pregabalin is indicated for management of neuropathic pain in adults, as adjunctive therapy for focal epilepsy in adults and as treatment of generalized anxiety disorder [1].

Pharmacokinetics and dosing

Pregabalin is not metabolized and is excreted renally unchanged [1]. Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and pregabalin drug exposure is similar between women and men [2]. In clinical trials, a patient’s sex has not shown to have any clinically significant influence on the plasma concentration of pregabalin [1]. A randomized controlled trial showed that women had a slightly smaller volume of distribution than men but this is not likely to be of clinical significance. Pregabalin oral clearance was independent of patient’s sex. The population estimate of Vd/F was dependent on body weight, which was accounted for by sex differences, with women having an approximately 20% lower value than men [3]. Despite the pharmacokinetic differences of pregabalin, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [1].

Effects

The anti-seizure efficacy of pregabalin has no clinically important sex differences, according to the pharmaceutical company [1].

Adverse effects

According to clinical trials conducted by the pharmaceutical company, men and women experienced similar adverse effects, regardless of indication. Weight gain (mainly due to peripheral edema) from pregabalin treatment has been shown to be related to dose and duration of exposure, but not with baseline BMI, patient’s sex or age [1].

In Sweden, between the years 2004 and 2006, two thirds of the patients in whom adverse events on pregabalin treatment were reported were women [4].

Reproductive health issues

The effect of pregabalin on sperm characteristics was evaluated in a randomized, double-blind, placebo-controlled study. Healthy men received 600 mg pregabalin (n=65) or placebo (n=62) for at least 8 weeks. Around 9% of the men receiving pregabalin and 3% of the men receiving placebo had ≥50% reduction in mean sperm concentrations. Pregabalin did not affect sperm morphology, sperm motility, serum FSH or serum testosterone levels, as compared to placebo [2].

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

Among incident users of pregabalin in Sweden (17 162 men, 27 258 women) between July 2006 and December 2009, men were more likely to be dispensed pregabalin at higher dose than the maximum allowed (adjusted OR 1.40) [5]. A small German study on pregabalin abuse or dependence report that the majority of patients were men (35 men, 8 women) [6].