CHF and arrhythmias:
Indications for ENTRESTO:
To reduce risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction; usually given with other therapies, in place of an ACEI or other ARB. To treat symptomatic heart failure with systemic left ventricular systolic dysfunction in children aged ≥1 year.
Initially 49mg/51mg twice daily; double the dose after 2–4 weeks to target maintenance dose of 97mg/103mg twice daily as tolerated. Not currently on ACEI/ARB, previously on low doses of ACEI/ARB, severe renal impairment (eGFR <30mL/min/1.73m2), or moderate hepatic impairment (Child-Pugh B): initially 24mg/26mg twice daily; double the dose every 2–4 weeks to target maintenance dose of 97mg/103mg twice daily as tolerated. If switching from or to an ACEI: allow 36 hour wash-out period between taking the two drugs.
<1yr: not established. Administer twice daily; adjust dose every 2 weeks as tolerated. ≥1yr: <40kg (use oral susp): initially 1.6mg/kg, titrate to 2.3mg/kg, then to target dose of 3.1mg/kg; ≥40–<50kg: initially 24mg/26mg, titrate to 49mg/51mg, then to target dose of 72mg/78mg; ≥50kg: initially 49mg/51mg, titrate to 72mg/78mg, then to target dose of 97mg/103mg. Not currently on ACEI/ARB, previously on low doses of ACEI/ARB, severe renal impairment (eGFR <30mL/min/1.73m2), or moderate hepatic impairment (Child-Pugh B): initiate at half the usual dose (for 40–50kg: initially 0.8mg/kg with oral susp); follow recommended dose escalation every 2 weeks. Preparation of oral susp: see full labeling.
History of angioedema related to previous ACE inhibitor or ARB therapy. Concomitant ACE inhibitors. Concomitant aliskiren in patients with diabetes.
Fetal toxicity may develop; discontinue if pregnancy is detected. Discontinue if angioedema occurs; do not re-administer. Give SC epinephrine for airway obstruction if indicated. Black patients may have higher risk of angioedema than non-Black patients. Avoid in hereditary angioedema. May cause symptomatic hypotension. Correct salt/volume depletion prior to initiation or start at a lower dose. Adjust concomitant diuretic or antihypertensive doses if hypotension occurs. Reduce dose or temporarily discontinue if hypotension persists. Monitor renal function in renal artery stenosis, severe CHF. Monitor serum creatinine and down-titrate or interrupt dose if significant renal dysfunction develops. Monitor for hyperkalemia esp. in severe renal impairment, diabetes, hypoaldosteronism, or high K+ diet. Severe hepatic impairment: not recommended. Neonates. Pregnancy (2nd & 3rd trimesters); consider alternative therapy. Nursing mothers: not recommended.
Neprilysin inhibitor + angiotensin II receptor blocker.
See Contraindications. Dual inhibition of the renin-angiotensin system: avoid concomitant with an ARB. Concomitant aliskiren in renal impairment (eGFR <60mL/min/1.73m2); avoid. Concomitant K+ supplements, K+ -sparing diuretics, K+ -containing salt substitutes may cause hyperkalemia. Worsening renal function and possible acute renal failure with NSAIDs, including selective COX-2 inhibitors (monitor renal function periodically in elderly and/or volume depleted). May increase lithium levels; monitor.
Hypotension, hyperkalemia, cough, dizziness, renal failure, increased serum creatinine, decreased hemoglobin/hematocrit.