Doxazosin

Additional information

Pharmacokinetics and dosing

No clinically relevant sex differences in pharmacokinetics have been observed at steady state with of 4 mg doxazosin once daily in a controlled-release gastrointestinal therapeutic system formulation (GITS) [1-3]. The Cmax and AUC were approximately 20% higher in women than men at steady state. However, after a single 4 mg dose, the Cmax and AUC 45% and 46% higher in women [3]. In a similar study stratified by age groups, the sex difference was only seen in the young group. Young women had higher Cmax and AUC than the rest of the study population; the AUC was 45% higher on day 1 (p<0.05) and 20% higher in day 7 when compared to young men. Further, the highest number of adverse effects were reported in young women, however the number of adverse effects declined with time and steady state was achieved [3]. Based on this, FDA’s clinical pharmacology reviewer considered that young women would benefit from dose-titration at doses lower than 4 mg due to the disproportionate high number of adverse effects and the sex differences in pharmacokinetic parameters. However, the 4 mg GITS is the lowest available dose, making dose titration not possible in young women. Further, the sex difference in AUC was possible due to a lower body weight in women [3]. In spite of this, no dose adjustment  according to sex [2] or age [3] is recommended.

Effects

In a clinical trial (74 men, 38 women) examining the effects of doxazosin 1 mg daily in patients with mild hypertension, blood pressure were reduced to a similar extent in men and women [4]. Also, doxazosin is used to reduce symptoms of benign prostatic hyperplasia in men [5].

Adverse effects

Clinical studies report that the type and incidence of adverse events from doxazosin were similar in men and women [1, 6]. However, there have been indications of an association between higher drug concentration and a higher risk of adverse events in women (see above under Pharmacokinetics and dosing).

Reproductive health issues

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

Other information

Several clinical trials have shown good results with the use of α1-blockers in the treatment of lower ureteral stones [6, 7]. A comparative prospective study (40 men, 40 women) evaluated the effects of doxazosin 4 mg once daily in patients with distal ureteral stones. The results showed no statistically significant difference in expulsion time, expulsion rate, and numbers of renal colic episodes among men and women. Safety and tolerability of the therapy were considered to be same in both sexes [6].

Doxazosin is used in men with erectile dysfunction, however with varying results [8].