Entresto

Reduce risk of CV death & hospitalization for heart failure in adults w/ chronic heart failure. Benefits are most clearly evident in patients w/ left ventricular ejection fraction below normal.

Starting dose: 100 mg bid. Dose should be doubled at 2-4 wk to the target dose of 200 mg bid as tolerated. Patient not currently taking an ACE inhibitor or an ARB or taking low dose of these medicinal products Starting dose of 50 mg bid & slow dose titration (doubling every 3-4 wk) are recommended. Patient w/ systolic BP ≥100-110 mmHg; moderate (eGFR 30-60 mL/min/1.73 m²) or severe (eGFR <30 mL/min/1.73 m²) renal impairment; moderate hepatic impairment (Child-Pugh class B) or w/ AST/ALT values >2 x ULN range Starting dose: 50 mg bid.

May be taken with or without food: Swallow whole w/ glass of water.

Hypersensitivity. History of angioedema related to previous ACE inhibitor or ARB therapy. Hereditary or idiopathic angioedema. Concomitant use w/ ACE inhibitors; do not administer until 36 hr after discontinuing ACE inhibitor therapy. Concomitant use w/ aliskiren-containing medicinal products in patients w/ DM or renal impairment (eGFR <60 mL/min/1.73 m²). Severe hepatic impairment, biliary cirrhosis & cholestasis. 2nd & 3rd trimester of pregnancy.

Discontinue immediately if angioedema occurs & provide appropriate therapy & monitoring until resolution of signs & symptoms; treatment must not be re-administered. Higher risk of angioedema in patients w/ prior history of angioedema; black patients. Do not initiate treatment unless systolic BP ≥100 mmHg. Routinely monitor BP when initiating therapy or during dose titration. Temporary down-titration or discontinuation is recommended if hypotension occurs. Correct Na &/or vol depletion before starting treatment. Do not initiate treatment if serum K level >5.4 mmol/L. Increased risk of hyperkalemia, although hypokalemia may also occur. Monitor serum K in patients w/ risk factors eg, renal impairment, DM, hypoaldosteronism, or those on a high K diet or on mineralocorticoid antagonists. Caution in patients w/ bilateral or unilateral renal artery stenosis (monitoring of renal function is recommended); w/ NYHA functional class IV. B-type natriuretic peptide is not a suitable biomarker of heart failure in patients treated w/ Entresto. Consider discontinuation if patient experiences psychiatric events eg, hallucinations, paranoia & sleep disorders, in context of psychotic events. Do not initiate Entresto until 36 hr after taking last dose of ACE inhibitor therapy, & vice versa. Not recommended in combination w/ direct renin inhibitors (eg, aliskiren). Should not be co-administered w/ another ARB-containing product. Minor influence on ability to drive & use machines. Caution in patients w/ severe renal impairment (eGFR <30 mL/min/1.73 m²); moderate hepatic impairment (Child-Pugh class B) or w/ AST/ALT values >2 x ULN range. Not recommended in patients w/ ESRD. Risk of decreased renal function which may be further increased by dehydration or concomitant use of NSAIDs. Not recommended during 1st trimester of pregnancy & during breast-feeding. Safety & efficacy in childn & adolescents <18 yr have not been established.

Hypotension, hyperkalemia & renal impairment; angioedema.

Risk of angioedema may be increased w/ ACE inhibitors. Higher frequency of adverse events (eg, hypotension, hyperkalemia & decreased renal function including acute renal failure) w/ aliskiren. May increase systemic exposure of OATP1B1 & OATP1B3 substrates eg, statins. Increased C_max & AUC of atorvastatin. Greater BP reduction w/ PDE5 inhibitors (eg, sildenafil) compared to Entresto alone. May lead to increases in serum K & creatinine w/ K-sparing diuretics (triamterene, amiloride), mineralocorticoid antagonists (spironolactone, eplerenone), K supplements, K-containing salt substitutes or other agents (eg, heparin). May lead to increased risk of worsening renal function w/ NSAIDs including selective COX-2 inhibitors in elderly patients, vol-depleted patients (including those on diuretic therapy), or those w/ compromised renal function. Reversible increases in serum lithium conc & toxicity. Reduced C_max & AUC of furosemide; metformin. Concomitant use w/ nitrates eg, nitroglycerine. Systemic exposure of sacubitril/valsartan may be increased w/ OATP1B1, OATP1B3, OAT3 (eg, rifampicin, ciclosporin), OAT1 (eg, tenofovir, cidofovir) or MRP2 (eg, ritonavir) inhibitors.

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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