Sacubitril And Valsartan

⛔ FDA Black Box Warning

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue sacubitril and valsartan tablets 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 ) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue sacubitril and valsartan tablets 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 )

Contraindications

4 CONTRAINDICATIONS Sacubitril and valsartan 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 )] • Hypersensitivity to any component. ( 4 ) • History of angioedema related to previous ACEi or ARB therapy. ( 4 ) • Concomitant use with ACE inhibitors. ( 4 , 7.1 ) • Concomitant use with aliskiren in patients with diabetes. ( 4 , 7.1 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Sacubitril and valsartan 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 (see Clinical Considerations). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. In animal reproduction studies, sacubitril and valsartan treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits (see Data) . When pregnancy is detected, consider alternative drug treatment and discontinue sacubitril and valsartan. 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and phys