Generic

Sacubitril + Valsartan

Indications

In patients with chronic heart failure (NYHA Class II-IV) with a decreased ejection fraction, this combination is suggested to minimize the risk of cardiovascular mortality and hospitalization for heart failure.

In lieu of an ACE inhibitor or other ARB, this combination is generally given in conjunction with other heart failure treatments.

Pharmacology

The active metabolite of sacubitril, LBQ657, inhibits enkephalinase, a neutral endopeptidase that normally cleaves natriuretic peptides, including: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricular pressure to activate posterior receptors, causing vasodilation, natriuresis, and diuresis. Under normal circumstances, enkephalinase degrades other vasodilator and vasoconstrictor peptides, such as angiotensin I and II, endothelin 1, and amyloid-β peptide. Therefore, neprilysin inhibition results in decreased degradation and increased concentration of endogenous natriuretic peptides and increased level of vasoconstrictor hormones such as angiotensin II. (However, when combined with valsartan, it causes angiotensin II and its receptors to be blocked, preventing vasoconstriction and leading to a decrease in vascular resistance and blood pressure.) The effects of sacubitril on the cardiovascular system and the kidneys are due to the usual peptides degraded by enkephalinase.

Valsartan is an oral medication that belongs to a class of drugs called angiotensin receptor blockers (ARB). It is a specific orally active angiotensin II antagonist that acts on the AT1 subtype. The binding of angiotensin to its receptors causes blood vessels to narrow (vasoconstriction), which leads to increased blood pressure (hypertension). Valsartan blocks angiotensin II receptors. By blocking the effects of angiotensin, valsartan dilates blood vessels and lowers blood pressure without affecting pulse rate. The affinity of valsartan for the AT1 receptor is much higher than that for the AT2 receptor (about 20,000 times). It does not bind to or block other hormone receptors or ion channels that are known to be important for cardiovascular regulation.

Dosage & Administration

The recommended starting dose of this combination is 49/51 mg twice-daily.

Double the dose of this combination after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Dose Adjustment For Patients Not Taking An ACE inhibitor Or ARB Or Previously Taking Low Doses Of These Agents.

A starting dose of 24/26 mg twice-daily is recommended for patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents. Double the dose of this combination every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Sacubitril & Valsartan is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to Sacubitril & Valsartan allow a washout period of 36 hours between administration of the two drugs.

Contraindications

• This combination is contraindicated:
• Hypersensitivity to any component in patients
• Having concurrent use of ACE inhibitors in individuals with a history of angioedema linked to previous ACE inhibitor or ARB treatment. Do not take within 36 hours of stopping or starting an ACE inhibitor.
• In individuals with diabetes who are also on aliskiren,

Side Effects

Other parts of the labeling list clinically important adverse events, such as: Hyperkalemia, Angioedema, Hypotension, Impaired Renal Function

Pregnancy & Lactation

Pregnancy: Inform patients of reproductive potential about the consequences of exposure to this combination during pregnancy. Discuss treatment options with women planning to become pregnant. Patients are required to report their pregnancy to the doctor as soon as possible.

Lactation period: There is no information on the presence of sacubitril/valsartan in human milk, its effect on nursing infants, or its effect on milk production. Sacubitril/valsartan is present in rat milk. Because exposure to sacubitril/valsartan may cause serious adverse reactions to breastfed infants, it is recommended that breastfeeding women do not recommend breastfeeding during treatment with sacubitril/valsartan.

Therapeutic Class

Combined antihypertensive preparations

Storage Conditions

Store at room temperature between 20°C to 25°C. Protect from moisture.

Pharmaceutical Name

General Pharmaceuticals Ltd.