Entresto

In conjunction w/ other heart failure therapies (in place of an ACE inhibitor or other ARB) to reduce the risk of CV death & hospitalization for heart failure in patients w/ chronic heart failure (NYHA class II-IV) & reduced ejection fraction. Treatment of essential HTN.

Heart failure Initially 100 mg bd, then double dose every 2-4 wk to the target dose of 200 mg bd, as tolerated by the patient. A starting dose of 50 mg bd is recommended for patients not currently taking an ACE inhibitor or ARB, & should be considered for patients previously taking low doses of these agents. Patient w/ severe renal impairment (eGFR <30 mL/min/1.73 m²) Initially 50 mg bd. Patient w/ moderate hepatic impairment (Child-Pugh B) Initially 50 mg bd. Essential HTN Initially 200 mg once daily, can be increased to 400 mg once daily. The heart failure dosing is recommended in hypertensive patients w/ heart failure. Patient w/ moderate hepatic impairment (Child-Pugh B) Initially 100 mg once daily.

May be taken with or without food.

Hypersensitivity. Hereditary angioedema. Known history of angioedema related to previous ACE inhibitor or ARB therapy. Concomitant use w/ ACE inhibitors. Concomitant use w/ aliskiren-containing products in patients w/ DM or renal impairment (eGFR <60 mL/min/1.73 m²). Severe renal impairment w/ eGFR <10 mL/min/1.73 m² & patients undergoing dialysis. Pregnancy.

Risk of dual blockade of the renin-angiotensin-aldosterone system through combined use of ACE inhibitors, ARBs, or direct renin inhibitors eg, aliskiren. Entresto must not be initiated until 36 hr after the last dose of ACE inhibitor therapy, & vice versa. Caution when co-administered w/ direct renin inhibitors eg, aliskiren. Do not co-administer w/ an ARB. Reports of symptomatic hypotension. Correct Na &/or vol depletion before starting treatment. May be associated w/ decreased renal function. Closely monitor serum creatinine, & down-titrate or interrupt treatment in patients who develop clinically significant decrease in renal function. May be associated w/ increased risk of hyperkalemia. Caution when co-administered w/ medications known to raise K levels. Monitor serum K, especially in patients w/ risk factors for hyperkalaemia. Reports of angioedema. Immediately discontinue treatment if angioedema occurs. Caution in patients w/ prior history of angioedema. May increase blood urea & serum creatinine levels in patients w/ bilateral or unilateral renal artery stenosis. Caution in patients w/ renal artery stenosis & monitor renal function. Safety & efficacy in essential HTN patients w/ severe renal impairment (eGFR <30 mL/min/1.73 m²) have not been established. Not recommended in patients w/ severe hepatic impairment (Child-Pugh C). Not recommended during breastfeeding. Female patients of child-bearing potential should use contraception during treatment & for 1 wk after the last dose. Safety & efficacy in ped patients <18 yr have not been established.

Heart failure: Hyperkalaemia; hypotension; renal impairment. Hypokalaemia; syncope, dizziness, headache; vertigo; orthostatic hypotension; cough; diarrhoea, nausea; renal failure; fatigue, asthenia. Essential HTN: Dizziness.

Concomitant use w/ ACE inhibitors may increase risk of angioedema. Combination w/ aliskiren is potentially associated w/ higher frequency of adverse events eg, hypotension, hyperkalemia & decreased renal function (including acute renal failure). Potentiated angiotensin II receptor blocking activity w/ other ARB. Increased systemic exposure of OATP1B1 & OATP1B3 substrates eg, statins. Co-administration w/ sildenafil or another PDE-5 inhibitor is associated w/ additional BP reduction. Concomitant use w/ K-sparing diuretics (eg, triamterene, amiloride), mineralocorticoid antagonists (eg, spironolactone, eplerenone), K supplements, or K-containing salt substitutes may lead to increased serum K & serum creatinine. Concomitant use w/ NSAIDs may lead to increased risk of worsening of renal function in elderly patients, vol-depleted patients (including those on diuretic therapy), or patients w/ compromised renal function. Risk of reversible increases in serum lithium conc & toxicity. Co-administration w/ inhibitors of OATP1B1, OATP1B3, OAT3 (eg, rifampin, cyclosporine) or MRP2 (eg, ritonavir) may increase systemic exposure to sacubitrilat or valsartan, respectively. Reduced C_max & AUC of furosemide; metformin.

Other Cardiovascular Drugs

C09DX04 - valsartan and sacubitril ; Belongs to the class of angiotensin II receptor blockers (ARBs), other combinations. Used in the treatment of cardiovascular disease.

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