Sacubitril + valsartan
Classification: AATC code: C09DX04
Summary
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.
Additional information
Pharmacokinetics and dosing
According to the original manufacturer, pharmacokinetics of valsartan/sacubitril is similar in men and women [1]. 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].
Effects
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.
Adverse effects
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 [4].
Reproductive health issues
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Updated: 2019-02-26
Date of litterature search: 2017-05-16
References
- Entresto (valsartan/sakubitril). Summary of Product Characteristics. European Medicines Agency (EMA); 2017.
- Gan L, Langenickel T, Petruck J, Kode K, Rajman I, Chandra P et al. Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor. J Clin Pharmacol. 2016;56:78-86. PubMed
- Ayalasomayajula S, Langenickel T, Pal P, Boggarapu S, Sunkara G. Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor. Clin Pharmacokinet. 2017;-:[Epub ahead of print]. PubMed
- Food and Drug Aministration (FDA). Clinical Pharmacology and Biopharmaceutics Review - ENTRESTO (sacubitril/valsartan). Food and Drug Administration [www]. [updated 2015-01-27, cited 2017-05-16]. länk
- McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2016 [cited 2017-05-20.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson