قرص زیوالس 49/51 میلی گرم

What is Zivales?
Sacubitril/ Valsartan is a medicine used to reduce the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic HF and treatment of symptomatic HF with systemic left ventricular systolic dysfunction in pediatric patients ≥1 year of age.

Product Information
Sacubitril/ Valsartan is an Angiotensin II Receptor Blocker/ Neprilysin Inhibitor that is used to reduce the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic HF. Benefits are most clearly evident in patients with left ventricular ejection fraction below normal, but it can be considered for use after optimizing mineralocorticoid-receptor antagonist and sodium-glucose transport protein 2 receptor antagonist therapies, particularly in patients with ejection fraction <55%, patients who remain hypertensive, or who were recently hospitalized for heart failure. 

What is the mechanism of action of Zivales?
Zivales contains sacubitril and valsartan. Sacubitril is a prodrug that with its active metabolite, inhibits an enzyme named neprilysin, leading to increased levels of peptides (molecules that consist of few amino acids) like natriuretic peptides inducing vasodilation and natriuresis. Valsartan is an antagonist of angiotensin II receptor that antagonizes angiotensin II induced aldosterone release and vasoconstriction. 

What are the indications of Zivales?
Adult: Reduce the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic HF. Benefits are most clearly evident in patients with left ventricular ejection fraction below normal.
Pediatric: Treatment of symptomatic HF with systemic left ventricular systolic dysfunction in pediatric patients ≥1 year of age.

What are the dosage forms of Zivales?
Zivales is available as 50, 100 and 200 mg film-coated tablets. 
Each 50 mg film-coated tablet contains sacubitril 24 mg and valsartan 26 mg.
Each 100 mg film-coated tablet contains sacubitril 49 mg and valsartan 51 mg.
Each 200 mg film-coated tablet contains sacubitril 97 mg and valsartan 103 mg.

Does Zivales need dose adjustment in kidney impairment?
Severe kidney impairment (eGFR <30 mL/minute/1.73 m2): It needs dose adjustment.

Does Zivales need dose adjustment in hepatic impairment?
Moderate impairment (Child-Pugh class B): It needs dose adjustment. Should be used with caution in patients with ascites due to cirrhosis. 
Severe impairment (Child-Pugh class C): Use is not recommended due to a lack of studies.

What are the contraindications of Zivales?
Avoid use in case of hypersensitivity to sacubitril and valsartan or any component of the formulation; history of angioedema related to previous Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) therapy; concomitant use or use within 36 hours of ACE inhibitors; concomitant use of aliskiren in patients with diabetes. 

Who should use Zivales with caution?
Angioedema: If angioedema occurs, discontinue sacubitril/ valsartan immediately, provide appropriate therapy, and monitor for airway compromise. Sacubitril/ Valsartan must not be re-administered. In cases of confirmed angioedema where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, administer appropriate therapy. 
Hypotension: Patients with an activated renin-angiotensin system, such as those being treated with high doses of diuretics), are at greater risk of hypotension. Correct volume or salt depletion prior to administration of sacubitril/ valsartan or start at a lower dose. If hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia). If hypotension persists despite such measures, reduce the dosage or temporarily discontinue sacubitril/ valsartan. Permanent discontinuation of therapy is usually not required.
Impaired Renal Function: In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACEIs and ARBs has been associated with oliguria, progressive azotemia and, rarely, acute renal failure. Closely monitor serum creatinine, and down-titrate or interrupt sacubitril/valsartan in patients who develop a clinically significant decrease in renal function. 
Hyperkalemia: Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption of sacubitril/ valsartan may be required. 
Use with caution in patients with significant aortic/ mitral stenosis.
Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully. 

What are the drug interactions of Zivales?
ACEIs: May enhance the adverse/ toxic effect of sacubitril. Specifically, the risk of angioedema may be increased with this combination. Avoid combination
Isocarboxazid: May enhance the antihypertensive effect of Antihypertensive Agents. Avoid combination.
Aliskiren: May enhance the hyperkalemic, hypotensive and nephrotoxic effects of ARBs. Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely.
Lithium: ARBs may increase the serum concentration of lithium. Initiate lithium at lower doses in patients receiving an ARB. Consider lithium dose reductions in patients stable on lithium therapy who are initiating an ARB. Monitor lithium concentrations closely when combined.

Is Zivales recommended during pregnancy and lactation?
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue sacubitril/ valsartan as soon as possible.
It is not known if sacubitril or valsartan is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended. 

FAQs
1-    Can Zivales be cut in half?
Zivales tablets are unscored, and taking half of a tablet of Zivales might contain uneven amounts of medicine.

2-    Why is Zivales produced as a combination of sacubitril/ valsartan?
In addition to the effect of sacubitril on increasing natriuretic peptides, induction of vasodilation, and natriuresis, valsartan in the combination tablet is more bioavailable than valsartan alone. 

3-    What are the advantages of Zivales to ARBs like valsartan in terms of adverse events?
Based on studies, increases in serum creatinine and severe hyperkalemia occurred less frequently than with ARB therapy alone.