CIDMUS is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure with a reduced ejection fraction

The recommended starting dose is 49/51 mg orally twice daily. Double the dose 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 In patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents, start CIDMUS at half the usual recommended starting dose. After initiation, increase the dose every 2 to 4 weeks in adults.

Dose Adjustment for Severe Renal Impairment in adults patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2 ), start CIDMUS at half the usual recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter.

No starting dose adjustment is needed for mild or moderate renal impairment.

Dose Adjustment for Hepatic Impairment In adults with moderate hepatic impairment (Child-Pugh B classification), start CIDMUS at half the usual recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter. No starting dose adjustment is needed for mild hepatic impairment. Use in patients with severe hepatic impairment is not recommended. 

1. Angioedema

2. Hypotension

3. Impaired Renal Function

4. Hyperkalemia

5. Hypersensitivity including rash, pruritus, and anaphylactic reaction

CIDMUS is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to CIDMUS allow a washout period of 36 hours between administration of the two drugs.

Pregnancy

CIDMUS can cause fetal harm when administered to a pregnant woman. The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. When pregnancy is detected, consider alternative drug treatment and discontinue CIDMUS.

Lactation 

There is no information regarding the presence of sacubitril/valsartan in human milk, the effects on the breastfed infant, or the effects on milk production. Sacubitril/valsartan is present in rat milk. Because of the potential for serious adverse reactions in breastfed infants from exposure to sacubitril/valsartan, advise a nursing woman that breastfeeding is not recommended during treatment with CIDMUS.

Geriatric Use

No relevant pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population.

Hepatic Impairment

No dose adjustment is required when administering CIDMUS to patients with mild hepatic impairment (Child-Pugh A classification). The recommended starting dose in patients with moderate hepatic impairment (Child-Pugh B classification) is 24/26 mg twice daily. The use of CIDMUS in patients with severe hepatic impairment (Child-Pugh C classification) is not recommended, as no studies have been conducted on these patients.

Renal Impairment

No dose adjustment is required in patients with mild (eGFR 60 to 90 mL/min/1.73 m2 ) to moderate (eGFR 30 to 60 mL/min/1.73 m2 ) renal impairment. The recommended starting dose in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2 ) is 24/26 mg twice daily.

• Dual Blockade of the Renin-Angiotensin-Aldosterone System Concomitant use of the drug with an ACE inhibitor is contraindicated because of the increased risk of angioedema. Avoid the use of CIDMUS with an ARB, because CIDMUS contains the angiotensin II receptor blocker valsartan. The concomitant use of CIDMUS with aliskiren is contraindicated in patients with diabetes. Avoid use with aliskiren in patients with renal impairment (eGFR < 60 mL/min/1.73 m²).

• Potassium-Sparing Diuretics - As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increase in serum potassium levels.

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with CIDMUS may result in worsening of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically.

• Lithium - Increases in serum lithium concentrations and lithium toxicity have been reported during the concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with CIDMUS.