SACUBITRIL AND VALSARTAN

AbsorptionFollowing oral administration, Sacubitril and valsartan tablets dissociates into sacubitril and valsartan. Sacubitril is further metabolized to LBQ657. The peak plasma concentrations of sacubitril, LBQ657, and valsartan are reached in 0.5 hours, 2 hours, and 1.5 hours, respectively. The oral absolute bioavailability of sacubitril is estimated to be greater than or equal to 60%. The valsartan in sacubitril and valsartan tablets is more bioavailable than the valsartan in other marketed ...

Dosing in clinical trials was based on the total amount of both components of sacubitril and valsartan, i.e., 24/26 mg, 49/51 mg, and 97/103 mg were referred to as 50 mg, 100 mg, and 200 mg, respectively. 14.1 Adult Heart Failure PARADIGM-HF PARADIGM-HF was a multinational, randomized, double-blind trial comparing sacubitril and valsartan tablets and enalapril in 8,442 adult patients with symptomatic chronic heart failure (NYHA class II–IV) and systolic dysfunction (left ventricular ejection fraction ≤ 40%). Patients had to have been on an ACE inhibitor or ARB for at least four weeks and on ma...

Clinically significant adverse reactions that appear in other sections of the labeling include:

• Angioedema [see Warnings and Precautions ( 5.2 )]
• Hypotension [see Warnings and Precautions ( 5.3 )]
• Impaired Renal Function [see Warnings and Precautions ( 5.4 )]
• Hyperkalemia [see Warnings and Precautions ( 5.5 )] Adverse reactions occurring greater than or equal to 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact X...

Sacubitril and valsartan tablets are contraindicated:

• in patients with hypersensitivity to any component
• in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy [see Warnings and Precautions ( 5.2 )]
• with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions ( 7.1 )]
• with concom...

• Observe for signs and symptoms of angioedema and hypotension. ( 5.2 , 5.3 )
• Monitor renal function and potassium in susceptible patients. ( 5.4 , 5.5 ) 5.1 Fetal Toxicity Sacubitril and valsartan tablets can cause fetal harm when administered to a pregnant woman. 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 altern...

7 DRUG INTERACTIONS

• Avoid concomitant use with aliskiren in patients with estimated glomerular filtration rate (eGFR) less than 60. ( 7.1 )
• Potassium-sparing diuretics: May lead to increased serum potassium. ( 7.2 )
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): May lead to increased risk of renal impairment. ( 7.3 )
• Lithium: Increased risk of lithium toxicity. ( 7.4 ) 7.1 Dual Blockade of...