erapy may be required.
Hepatic disease
Administration of sacubitril; valsartan is not recommended in patients with severe hepatic disease (Child-Pugh class C), as no studies have been conducted in these patients. Dose adjustments are recommended in patients with moderate hepatic disease (Child-Pugh class B); no dose adjustment is required when administering sacubitril; valsartan to patients with mild hepatic impairment (Child-Pugh class A).
Children, infants, neonates
The safety and efficacy of sacubitril; valsartan has not been in established in adolescents, children, infants, or neonates.
Pregnancy
Sacubitril; valsartan can cause fetal harm when administered to a pregnant woman. Once pregnancy is detected, every effort should be made to discontinue sacubitril; valsartan and consider alternative therapy. When used during second and third trimesters, drugs that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists), including valsartan, can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported; it is attributed to decreased fetal renal function and is associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. If pregnancy occurs during therapy and the drug is considered lifesaving to the mother and there is no appropriate alternative therapy, advise the pregnant woman of the potential risk to the fetus. While it was previously thought that adverse effects do not result from first-trimester drug exposure, an observational study based on Tennessee Medicaid data reported that the risk of congenital malformations is significantly increased during first-trimester exposure to ACE inhibitors. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Ultrasound examination should be performed to assess the intra-amniotic environment, and fetal testing may be appropriate, based on week of gestation. Patients and physicians should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates and infants with histories of in utero exposure to sacubitril; valsartan for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.
Breast-feeding
It is not known if sacubitril; valsartan is excreted in human milk, and there is no information on the effects of sacubitril; valsartan on a breastfed infant or the effects on milk production. Sacubitril; valsartan is present in rat milk. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended during treatment with sacubitril; valsartan. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug |
