Bendroflumetiazid

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of bendroflumethiazide have been found.

Effects

The large Medical Research Council (MRC) trial of treatment of mild hypertension (7513 men, 6945 women) compared treatment with bendroflumethiazide and propranolol. Results showed a benefit associated with bendroflumethiazide treatment in men, but the opposite effect in women. All-cause mortality rates were: 7.5% deaths in bendroflumethiazide-treated men compared with 8.2% in placebo-treated men; 4.5% deaths in bendroflumethiazide-treated women compared with 3.5% on placebo [1].

Adverse effects

Adverse reactions to bendroflumethiazide were evaluated in a sub-analysis of theMRC treatment trial. Patients received 5 mg bendroflumethiazide twice daily. Men had significantly higher incidences of gout and of impotence, compared with controls. After 5 years, 17.1% of the men had been withdrawn from treatment with bendroflumethiazide compared with 12.8% of the women (p<0.05). The difference is mainly due to the higher incidences of impotence and gout in men [2].

Studies have reported a fall in serum potassium concentration in patients taking bendroflumethiazide, but there are conflicting results whether there are sex differences [2-4]. In the MRC trial, mean serum potassium concentration fell to a similar level in men and women after 3 years of treatment with bendroflumethiazide [2]. Also, one retrospective study (158 men, 231 women) found that the serum potassium concentration in patients treated with bendroflumethiazide was not related to sex [3]. However, in another retrospective study (91 men, 102 women), women had lower serum potassium concentration than men after taking bendroflumethiazide 5 mg daily. Serum potassium remained significantly related to patient’s sex independent of body weight. The etiology of this sex difference is not known, but it may reflect a general tendency for women to develop hypokalemia which is not specifically related to diuretics. Severe hypokalemia was uncommon and showed no difference between the sexes [4].

Reproductive health issues

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

Other information

In a clinical trial (62 men, 23 women), bendroflumethiazide was administrated to patients with recurrent calcium oxalate urinary stone disease. Twenty-two men and four women (31%) stopped treatment within the first two years because of side effects. Symptoms divided by sex were not shown [5].