sacubitril + valsartan: clinical use

Prescribing considerations

• Confirm the licensed heart-failure phenotype and review previous ACE inhibitor or ARB treatment before initiation.
• Assess volume status and susceptibility to symptomatic hypotension, particularly with renal impairment, older age, diuretics, vomiting or diarrhoea.
• Use caution in significant renal impairment and moderate hepatic impairment; there is no experience in end-stage renal disease.
• Film-coated tablets are unsuitable for children weighing less than 40 kg; granules provide an alternative formulation.

Contraindications and cautions

• Concomitant ACE inhibitor use or initiation before completion of the required washout period
• Previous ACE inhibitor- or ARB-related angioedema, or hereditary or idiopathic angioedema
• Aliskiren use in patients with diabetes or renal impairment below the specified eGFR threshold
• Severe hepatic impairment, biliary cirrhosis or cholestasis
• Second or third trimester of pregnancy
• Hypersensitivity to an active substance or excipient

Monitoring

• Blood pressure and symptoms of hypotension
• Renal function and hydration status
• Serum potassium, particularly with renal impairment, diabetes or potassium-raising medicines
• Angioedema and uncommon neuropsychiatric events
• Use NT-proBNP rather than BNP when interpreting natriuretic peptides, because neprilysin inhibition affects BNP

Clinical pharmacology

Sacubitril is a prodrug converted to LBQ657, which inhibits neprilysin; valsartan blocks the angiotensin II AT1 receptor. The components are highly protein-bound, and valsartan exposure from this combination differs from conventional valsartan formulations.

Formulation and product differences

• Film-coated tablets should be swallowed with water and should not be split or crushed.
• Granule capsules must be opened; their contents are sprinkled onto soft food and consumed immediately. The shells are not swallowed.
• The granule formulation is licensed for paediatric heart failure and supports administration where tablets are unsuitable.