Drug products: Entresto®
ATC code: C09DX04
The substance sacubitril is given as fixed combination with the angiotensin II inhibitor valsartan. Studies conducted by the manufacturer report no differences between men and women in efficacy or safety of valsartan/sacubitril. Other published studies on sex differences in efficacy and safety are lacking.
In our opinion, the present evidence does not motivate differentiation in dosing or treatment between men and women.
According to the original manufacturer, pharmacokinetics of valsartan/sacubitril is similar in men and women . A study in healthy adults receiving 400 mg oral single dose valsartan/sacubitril (19 men, 17 women) showed no sex or age differences in pharmacokinetics [2, 3]. Dose adjustment based on age or sex is not considered necessary [2, 4].
According to a study sponsored by the manufacturer, sub-group analyses on primary efficacy endpoint of cardiovascular death or hospitalization for worsening heart failure was shown to be consistent across all subpopulations, including sex, for valsartan/sacubitril compared to enalapril [4, 5]. No placebo-controlled efficacy studies with a clinically relevant sex analysis have been found.
In a pivotal phase III study conducted by the manufacturer, valsartan/sacubitril was safe and well tolerated in men and women and in patients >65 years. Safety of valsartan/sacubitril in patients below 18 years has not been evaluated .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2017-05-16
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson