Effect of Combo Heart Failure Drug on Concomitant Furosemide Examined

Sacubitril/valsartan is approved for the treatment of heart failure and reduced ejection fraction
Sacubitril/valsartan is approved for the treatment of heart failure and reduced ejection fraction

Findings from an open-label study evaluating the effect of sacubitril/valsartan on the pharmacokinetics (PK) and pharmacodynamics (PD) of furosemide showed no significant impact among healthy patients. The study was published in Pharmacokinetic Dynamic Relationships.

Sacubitril/valsartan (marketed as EntrestoNovartis) is approved to treat heart failure and reduced ejection fraction (HFrEF).  Furosemide, a loop diuretic, is commonly prescribed to patients with HFrEF who may also be taking sacubitril/valsartan.

Researchers conducted a 2-period, single-sequence study (N=28) in which healthy subjects received single dose of oral furosemide 40mg following a 2-day washout in Period 1. During Period 2, sacubitril/valsartan 200mg was given twice daily for 5 days and co-administered with furosemide 40mg on Day 6. Patients' plasma and urine samples were obtained to analyze the PK of furosemide and sacubitril/valsartan and the PD of furosemide. 

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The data showed sacubitril/valsartan antagonized plasma Cmax (estimated geometric mean ratio 0.50, 90% CI: 0.44, 0.56), plasma AUCinf (0.72, 90% CI: 0.67, 0.77) and 24-hour urinary excretion of furosemide (0.74, 90% CI: 0.69, 0.79).  When given with sacubitril/valsartan, diuresis was reduced in response to furosemide: 0–4 hours (~7%), 4–8 hours(21%), and 0–24 hours (0.2%); natriuresis was reduced by ~28.5%, 7%, and 15%, respectively. 

Based on the findings, the authors concluded that sacubitril/valsartan decreased plasma Cmax, AUC, and 24-hour urinary excretion of furosemide "while not significantly impacting its pharmacodynamic effects in healthy subjects." 

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