Drug products: Amlarrow, Amlobesyl, Amlodipin Accord, Amlodipin Actavis, Amlodipin Aurobindo, Amlodipin Bluefish, Amlodipin BMM Pharma, Amlodipin Hexal, Amlodipin Jubilant, Amlodipin Krka, Amlodipin Medical Valley, Amlodipin Orifarm, Amlodipin ratiopharm, Amlodipin Sandoz, Amlodipin STADA®, Amlodipin/Valsartan 2care4, Amlodipin/Valsartan Ebb, Amlodipin/Valsartan Krka, Amlodipin/Valsartan STADA, Amlodipine, Amlodipine Teva, Amlodipine Vitabalans, Amlodistad, Amloratio, Amlori, Exforge®, Milodimyl, Norvasc, Norvasc®
ATC code: C08CA01, C09DB01
Substances: amlodipine, amlodipine besylate, amlodipine maleate, amlodipine mesilate, amlodipine mesylate monohydrate
Clinical studies have shown contradictory results whether there are sex differences or not in blood pressure reduction by amlodipine.
A common adverse effect of amlodipine is edema, mainly peripheral edema, and occurs more often among women.
In a single-dose bioequivalence study comparing two forms of amlodipine in healthy volunteers (18 men, 18 women), women had a slightly higher bioavailability compared with men. The difference disappeared after adjusting for weight . The clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested .
Studies analyzing sex differences in blood pressure reduction (BP) after amlodipine treatment report contradictory results. Clinical trials have reported a greater BP reduction with amlodipine in women compared with men [9-12]. 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 . Also in the bioequivalence study mentioned earlier , 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 men and women, although decreases in systolic BP were more pronounced in men [5, 13]. Also, another clinical trial found a slightly less BP reduction in women compared with men .
Clinical trials have report similar incidence of adverse events in men and women [7, 11]. In the Amlodipine Cardiovascular Community Trial , the most common adverse event was edema (mainly peripheral edema) which occurred in 24% of treated patients and was more common in women. Mainly peripheral edema is associated with amlodipine treatment . A few cases, most men, of gingival overgrowth have been reported , but no significant difference between men and women has been shown .There are conflicting results from studies reporting that calcium channel blockers could be associated with cancer [1-5]. One case-control study has reported suspected increase in breast cancer in women taking calcium channel blockers , however the study was criticized due to methodological problems.
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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 .
Date of litterature search: 2019-04-25
Reviewed by: Diana Rydberg, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson