Valsartan, Sacubitril (Uperio) Tablets Pharmacodynamics
Mechanism of Action
The action of Valsartan, Sacubitril (Uperio) tablets is mediated by a novel mechanism. It involves simultaneous inhibition of neprilysin activity (NEP) by sacubitrilat (active metabolite of sacubitril) and blockade of angiotensin II type 1 receptors (AT1) by valsartan, an angiotensin II receptor antagonist (ARA II).
Under the influence of sacubitrilat, there is an increase in neprilysin degradable peptides, including natriuretic peptides (NUPs). This results in complementary cardiovascular and renal benefits in patients with heart failure. NUPs activate guanylyl cyclase-conjugated receptors, leading to vasodilation, increased natriuresis and diuresis, improved renal function, and more.
Valsartan, Sacubitril (Uperio) tablets are indicated for chronic heart failure (NYHA class II-IV) in patients with systolic dysfunction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.
They are used in combination therapy with other drugs as a substitute for angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARA II).
- Hypersensitivity to sacubitril, valsartan, or other excipients.
- Concomitant use with ACE inhibitors within 36 hours of ACE withdrawal.
Dosage and Administration
- Dosing of Valsartan, Sacubitril (Uperio) tablets is not influenced by food intake timing.
- The target daily dose is 200 mg (102.8 mg sacubitrilat + 97.2 mg valsartan) taken twice a day.
Patients in Special Categories
- Patients with Impaired Renal Function: Dosage adjustments may be necessary for patients with mild to severe renal impairment. Caution is advised in patients with severe renal impairment due to limited data.
- Patients with Hepatic Impairment: Dosage adjustments are recommended for patients with moderate hepatic impairment. Valsartan, Sacubitril (Uperio) tablets are not recommended for use in patients with severe hepatic impairment.
- Administration in Children and Adolescents: There are no data on the safety and efficacy of Valsartan, Sacubitril (Uperio) tablets in children and adolescents.
- Use in Patients Over 65 Years of Age: No dose adjustment is required for patients over 65 years of age.