General Pharmaceuticals Ltd.

Description:

IndicationsThis combination is recommended for patients with chronic heart failure (NYHA Class II-IV) and a decreased ejection fraction to reduce the risk of cardiovascular mortality and hospitalization for heart failure.This combination is typically used in conjunction with other heart failure treatments instead of an ACE inhibitor or other ARB.PharmacologyLBQ657, a sacubitril active metabolite, inhibits enkephalinase, a neutral endopeptidase that normally cleaves natriuretic peptides such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) (CNP). Under atrial and ventricular pressure, ANP and BNP are released to activate posterior receptors, resulting in vasodilation, natriuresis, and diuresis. Enkephalinase normally degrades other vasodilator and vasoconstrictor peptides like angiotensin I and II, endothelin 1, and amyloid-peptide. As a result, neprilysin inhibition reduces the degradation and concentration of endogenous natriuretic peptides while increasing the level of vasoconstrictor hormones such as angiotensin II. (However, when combined with valsartan, it inhibits angiotensin II and its receptors, preventing vasoconstriction and lowering vascular resistance and blood pressure.)Sacubitril’s effects on the cardiovascular system and the kidneys are caused by the usual peptides degraded by enkephalinase.Valsartan is an oral medication that belongs to the angiotensin receptor blocker class of drugs (ARB). It is an angiotensin II antagonist that acts specifically on the AT1 subtype. Angiotensin binding to its receptors causes blood vessels to constrict (vasoconstriction), resulting in increased blood pressure (hypertension). Valsartan works by blocking angiotensin II receptors. Valsartan dilates blood vessels and lowers blood pressure by blocking the effects of angiotensin without affecting pulse rate. Valsartan has a much higher affinity for the AT1 receptor than the AT2 receptor (about 20,000 times). It does not bind to or block other known hormone receptors or ion channels involved in cardiovascular regulation.?Dosage & AdministrationThe 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.

For patients who are not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and have previously taken low doses of these agents, a starting dose of 24/26 mg twice daily is recommended. Every 2 to 4 weeks, double the dose of this combination to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.When combined with an angiotensin-converting enzyme (ACE) inhibitor, sacubitril, and valsartan are contraindicated. Allow a 36-hour washout period between administrations of Sacubitril and Valsartan if switching from an ACE inhibitor.ContraindicationsContraindications apply to this combination:Patients’ hypersensitivity to any componentthose who have a history of angioedema associated with a prior ACE inhibitor or ARB treatment using ACE inhibitors concurrently. In the 36 hours following the start or cessation of an ACE inhibitor, do not take it.Those who have diabetes and are on an aliskiren may experienceSide EffectsCoughDizzinessOrthostatic hypotension (sudden lowering of blood pressure on standing)Altered levels of potassium in the bloodDecreased red blood cell countDecreased blood pressureImpaired Renal FunctionHypoglycemia (low blood glucose level)DiarrheaFaintingAngioedemaHypotensionHeadacheNauseaStomach painHyperkalemiaVertigoWeaknessPregnancy & LactationPregnancy: 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 in breastfed infants, it is recommended that breastfeeding women do not recommend breastfeeding during treatment with sacubitril/valsartan.Precaution & WarningAlong with taking this medication, you should continue to be active (mild walking, stretching) and consume a balanced, low-sodium diet.If you’ve been sitting or lying down, get up slowly to lessen the likelihood that you’ll feel lightheaded.The amount of potassium in your blood could increase as a result. Steer clear of potassium supplements and meals like bananas and broccoli.If you have a history of liver or renal problems, let your doctor know.Storage ConditionsStore at room temperature between 20?C to 25?C. Protect from moisture.