ENTRESTO™ (sacubitril and valsartan) tablets, for oral use
Initial U.S. Approval: 2015
BRIEF SUMMARY: Please see package insert for full prescribing information.
WARNING: FETAL TOXICITY
• When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1)
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing
fetus (5.1)
1 INDICATIONS AND USAGE
1.1 Heart Failure
ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in
patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE
inhibitor or other ARB.
4 CONTRAINDICATIONS
ENTRESTO is 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 concomitant use of aliskiren in patients with diabetes [see Drug Interactions (7.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Fetal Toxicity
ENTRESTO 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 alternative drug treatment and discontinue ENTRESTO. However, if there is no appropriate alternative to therapy
with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother,
advise a pregnant woman of the potential risk to the fetus [see Use in Specific Populations (8.1)].
5.2 Angioedema
ENTRESTO may cause angioedema. In the double-blind period of PARADIGM-HF, 0.5% of patients
treated with ENTRESTO and 0.2% of patients treated with enalapril had angioedema [see Adverse Reactions (6.1)]. If angioedema occurs, discontinue ENTRESTO immediately, provide appropriate therapy,
and monitor for airway compromise. ENTRESTO must not be re-administered. In cases of confirmed
angioedema where swelling has been confined to the face and lips, the condition has generally resolved
without treatment, although antihistamines have been useful in relieving symptoms.
Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue,
glottis or larynx, likely to cause airway obstruction, administer appropriate therapy, e.g., subcutaneous
epinephrine/adrenaline solution 1:1000 (0.3 mL to 0.5 mL) and take measures necessary to ensure
maintenance of a patent airway.
ENTRESTO has been associated with a higher rate of angioedema in Black than in non-Black patients.
Patients with a prior history of angioedema may be at i