Amlodipin

Additional information

Pharmacokinetics and dosing

In a single-dose bioequivalence study comparing two forms of amlodipine in healthy volunteers (18 men, 18 women), women had a slightly higher bioavailability of amlodipine compared with men. The difference disappeared after adjusting for weight [2]. The clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [3].

Effects

There are conflicting results whether men or women have more blood pressure (BP) reduction with amlodipine therapy. Clinical trials have reported a greater BP reduction with amlodipine in women compared with men [4-6]. The Amlodipine Community Trial (702 men, 382 women) observed that women had a greater absolute decrease in BP compared with men following amlodipine therapy (5-10 mg/day for 12 weeks). The percentage of patients achieving goal BP was higher in women than in men (91.4% vs. 83.0%). Reasons for these sex differences could be due to several mechanisms [4]. Also in the study by Abad-Santos et al. [3], women demonstrated a more pronounced reduction in systolic BP than men. The clinical significance of the sex difference remains to be determined.Contrary to these findings, the large randomized double-blind ALLHAT study (17 719 men, 15 638 women) reported that the achieved BP reductions from amlodipine therapy (20 mg/day) were comparable in both sexes, although decreases in systolic BP were more pronounced in men [7]. Also, another clinical trial found a slightly less BP reduction in women compared with men [8].

Adverse effects

Clinical trials have report similar incidence of adverse events in men and women [2,6]. In the Amlodipine Cardiovascular Community Trial [4], the most common adverse event was edema which occurred in 24% of treated patients, and was more common in women. A few cases, most men, of gingival overgrowth have been reported [9], but no statistically significant difference between the sexes has been shown [10].There are conflicting results from studies reporting that calcium channel blockers could be associated with cancer. One study reported suspected increase in breast cancer in women taking calcium channel blockers; however the study was criticised due to methodological problems of the study [1].

Reproductive health issues

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

Other information

A randomized clinical trial (76 men, 61 women) found that BP response to amlodipine among African-American men and women with early hypertensive nephrosclerosis appears to be determined by CYP4A4 genotypes and sex specificity may be an important consideration [11].