Tablets or Oral Suspension (suspension indicated where applicable)
- PO (Adults ): Sacubitril 49 mg/valsartan 51 mg twice daily initially; double dose in 2–4 wk to target dose of sacubitril 97 mg/valsartan 103 mg, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Sacubitril 24 mg/valsartan 26 mg twice daily initially; double dose every 2–4 wk to target dose of sacubitril 97 mg/valsartan 103 mg, as tolerated.
- PO (Children ≥1 yr and ≥50 kg): Sacubitril 49 mg/valsartan 51 mg twice daily initially; ↑ dose in 2 wk to sacubitril 72 mg/valsartan 78 mg twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 97 mg/valsartan 103 mg twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Sacubitril 24 mg/valsartan 26 mg twice daily initially; ↑ dose in 2 wk to sacubitril 49 mg/valsartan 51 mg twice daily, as tolerated; then ↑ dose again in 2 wk to sacubitril 72 mg/valsartan 78 mg twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 97 mg/valsartan 103 mg twice daily, as tolerated.
- PO (Children ≥1 yr and 40–<50 kg): Sacubitril 24 mg/valsartan 26 mg twice daily initially; ↑ dose in 2 wk to sacubitril 49 mg/valsartan 51 mg twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 72 mg/valsartan 78 mg twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: 0.8 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily initially; ↑ dose in 2 wk to 1.6 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose in 2 wk to 2.3 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of 3.1 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated.
- PO (Children ≥1 yr and <40 kg): 1.6 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily initially; then ↑ dose in 2 wk to 2.3 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of 3.1 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: 0.8 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily initially; ↑ dose in 2 wk to 1.6 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose in 2 wk to 2.3 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of 3.1 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated.
Hepatic/Renal Impairment
- PO (Adults ): Severe renal impairment (CCr <30 mL/min/1.73 m2) or moderate hepatic impairment: Sacubitril 24 mg/valsartan 26 mg twice daily initially; double dose every 2–4 wk to target dose of sacubitril 97 mg/valsartan 103 mg, as tolerated.
Hepatic/Renal Impairment
- PO (Children ≥1 yr and ≥50 kg): Severe renal impairment (CCr <30 mL/min/1.73 m2) or moderate hepatic impairment : Sacubitril 24 mg/valsartan 26 mg twice daily initially; ↑ dose in 2 wk to sacubitril 49 mg/valsartan 51 mg twice daily, as tolerated; then ↑ dose again in 2 wk to sacubitril 72 mg/valsartan 78 mg twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 97 mg/valsartan 103 mg twice daily, as tolerated.
Hepatic/Renal Impairment
- PO (Children ≥1 yr and 40–<50 kg): Severe renal impairment (CCr <30 mL/min/1.73 m2) or moderate hepatic impairment: 0.8 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily initially; ↑ dose in 2 wk to 1.6 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose in 2 wk to 2.3 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of 3.1 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated.
Hepatic/Renal Impairment
- PO (Children ≥1 yr and <40 kg): Severe renal impairment (CCr <30 mL/min/1.73 m2) or moderate hepatic impairment: 0.8 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily initially; ↑ dose in 2 wk to 1.6 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose in 2 wk to 2.3 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of 3.1 mg/kg (represents combined amount of sacubitril and valsartan) of oral suspension twice daily, as tolerated.
Oral Pellets
- PO (Children ≥1 yr and 34–<50 kg): Sacubitril 30 mg/valsartan 32 mg (using two sacubitril 15 mg/valsartan 16 mg capsules) twice daily initially; ↑ dose in 2 wk to sacubitril 45 mg/valsartan 48 mg (using three sacubitril 15 mg/valsartan 16 mg capsules) twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 60 mg/valsartan 64 mg (using four sacubitril 15 mg/valsartan 16 mg capsules) twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Use oral suspension (see above for dosing information).
- PO (Children ≥1 yr and 26–<34 kg): Sacubitril 24 mg/valsartan 24 mg (using four sacubitril 6 mg/valsartan 6 mg capsules) twice daily initially; ↑ dose in 2 wk to sacubitril 30 mg/valsartan 32 mg (using two sacubitril 15 mg/valsartan 16 mg capsules) twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 45 mg/valsartan 48 mg (using three sacubitril 15 mg/valsartan 16 mg capsules) twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Use oral suspension (see above for dosing information).
- PO (Children ≥1 yr and 19–<26 kg): Sacubitril 18 mg/valsartan 18 mg (using three sacubitril 6 mg/valsartan 6 mg capsules) twice daily initially; ↑ dose in 2 wk to sacubitril 24 mg/valsartan 24 mg (using four sacubitril 6 mg/valsartan 6 mg capsules) twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 30 mg/valsartan 32 mg (using two sacubitril 15 mg/valsartan 16 mg capsules) twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Use oral suspension (see above for dosing information).
- PO (Children ≥1 yr and 13–<19 kg): Sacubitril 12 mg/valsartan 12 mg (using two sacubitril 6 mg/valsartan 6 mg capsules) twice daily initially; ↑ dose in 2 wk to sacubitril 18 mg/valsartan 18 mg (using three sacubitril 6 mg/valsartan 6 mg capsules) twice daily, as tolerated; then ↑ dose again in 2 wk to target dose of sacubitril 24 mg/valsartan 24 mg (using four sacubitril 6 mg/valsartan 6 mg capsules) twice daily, as tolerated. Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Use oral suspension (see above for dosing information).
- PO (Children ≥1 yr and <13 kg): Use oral suspension (see above for dosing information). Patients not currently receiving ACE inhibitors or angiotensin II receptor blockers or receiving low doses of these agents: Use oral suspension (see above for dosing information).
Therapeutic Classification: vasodilators, heart failure agents
Pharmacologic Classification: angiotensin II receptor antagonists, neprilysin inhibitors
Sacubitril
Absorption: ≥60% absorbed following oral administration.
Distribution: Widely distributed to tissues.
Protein Binding: 94–97%.
Metabolism/Excretion: Rapidly converted to LBQ657, its active form. LBQ657 is not significantly metabolized; 52–68% excreted in urine, primarily as LBQ657; 37–48% excreted in feces, primarily as LBQ657.
Half-Life: Sacubitril: 1.4 hr. LBQ657: 11.5 hr.
Valsartan
Absorption: Absorption in combinations with sacubitril is more compared to oral administration of single-entity formulation.
Distribution: Widely distributed to tissues
Protein Binding: 94–97%.
Metabolism/Excretion: Minimally metabolized by the liver; 13% excreted in urine; 86% in feces.
Half-Life: 9.9 hr.
sa-KU-bi-tril/val-SAR-tan