Drug products: Enalapril Actavis, Enalapril Alpharma, Enalapril Astimex, Enalapril comp ratiopharm, Enalapril Comp Sandoz, Enalapril Comp STADA®, Enalapril Copyfarm, Enalapril Durascan, Enalapril Krka, Enalapril Mylan, Enalapril Orion, Enalapril Ranbaxy, Enalapril ratiopharm, Enalapril Sandoz, Enalapril STADA®, Enalapril Teva, Enalapril Vitabalans, Enalapril/Hydrochlorothiazide 2care4, Enalapril/Hydrochlorothiazide Mylan, Enalapril/Hydrochlorothiazide Orion, Enalapril/Hydrochlorothiazide Teva, Enap, Linatil, Linatil comp, Linatil comp mite, Renitec®, Renitec® comp., Synerpril®
ATC code: C09AA02, C09BA02
Substances: enalapril, enalapril maleate, enalaprilate
There are no clinically relevant sex differences described in pharmacokinetics or efficacy of enalapril described. Cough is a common non-dose dependent side effect of ACE-inhibitors which is more common in women. Angiotensin receptor blockers may then be an alternative.
No studies with a clinically relevant sex analysis regarding the pharmacokinetics of enalapril have been found. In a clinical study involving 110 hypertensive pediatric patients 6-16 years of age, the dose-dependent antihypertensive efficacy of enalapril was similar in boys and girls .
A small clinical trial (10 boys, 12 girls) has shown that adolescent girls with type 1 diabetes mellitus respond more favorably to ACE inhibitors than adolescent boys. Glomerular hyperfiltration is a factor for development of diabetic renal disease, and is influenced by hyperglycemia and RAS blockade. Twenty-two adolescents with type 1 diabetes mellitus were studied before and after ACE inhibition. After 21 days of treatment with enalapril (0.1 mg/kg daily x 1 week and then 0.1 mg/kg twice a day for 2 weeks), the renal responses to ACE inhibition differed between boys and girls . Only girls received beneficial reductions in GFR (glomerular filtration rate) and FF (filtration fraction). This may be due to a synergistic effect of ACE inhibitors and estrogen on components of the RAS. Even though the experiments in this study were carried out during the follicular (low estrogen) phase of the menstrual cycle, an augmented response to ACE inhibitors were noted in girls, suggesting that any levels of estrogen may act synergistically with RAS blockade . An interaction between ACE inhibitors and estrogen has also been discussed .
A randomized controlled trial (46 men, 37 women) studied long-term effects of enalapril on plasma levels of the fibrinolytic factors tissue plasminogen activator (tPa), plasminogen activator inhibitor (PAI-1), tPA/PAI-1 complex and vWF in both sexes with uncomplicated myocardial infarction. Enalapril or placebo was initiated two months or later following an acute myocardial infarction. Initial dose was 2.5 mg enalapril once daily with increasing dosage every three days. Plasma levels of tPA decreased significantly after two weeks enalapril treatment in both sexes, but tPa/PAI-1 complex decreased significantly only in women .
Several studies have reported a female predominance in the prevalence of ACE inhibitor induced cough [1-9]. The pathogenesis of the cough reaction is unknown. Different threshold for coughing in men and women have been proposed , as well as ethnic differences in cough tendency . One study suggests that sex hormones do not have any influence on cough, since most of the women in the study were postmenopausal .In a double-blind placebo-controlled study (SOLVD), adverse effects of enalapril analyzed (5794 men, 975 women). The most pronounced sex difference among reported side effects in the enalapril group was cough, which was more frequently reported by women (10.0% vs. 4.2%; odds ratio 2.38) .A review has examined ACE inhibitor-associated angioedema/urticaria; the number of reports among patients taking enalapril (mean dose 13 mg daily) were 13/11841 men and 10/13672 women .
Swedish users, please consult Janusmed Interactions (Janusmed interaktioner).
Enalapril should not be used in pregnant women. Swedish users, please consultJanusmed Drugs and Birth Defects (Janusmed fosterpåverkan).
Date of litterature search: 2013-10-28
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson