Aliskiren-valsartan has been assigned to pregnancy category D by the FDA. Aliskiren-valsartan contains both aliskiren (a direct renin inhibitor) and valsartan (an angiotensin II receptor blocker). When administered during the second or third trimester of pregnancy, drugs that act directly on the renin-angiotensin-aldosterone system can cause fetal and neonatal morbidity and death. Aliskiren-valsartan can cause fetal harm when administered to a pregnant woman. If aliskiren-valsartan is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Angiotensin II receptor agonists, like valsartan, and angiotensin-converting enzyme (ACE) inhibitors exert similar effects on the renin-angiotensin-aldosterone system. In several dozen published cases, ACE inhibitor use during the second and third trimesters of pregnancy was associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios was also reported, presumably from decreased fetal renal function. In this setting, oligohydramnios was associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus were also reported, although it is not clear whether these occurrences were due to exposure to the drug. In addition, first trimester use of ACE inhibitors, a specific class of drugs acting on the renin-angiotensin-aldosterone system, has been associated with a potential risk of birth defects in retrospective data.

When pregnancy occurs in a patient using aliskiren-valsartan, the drug should be discontinued as soon as possible. The patient should be informed of the potential risks to the fetus based on the time of gestational exposure to aliskiren-valsartan (first trimester only or later). If exposure occurs beyond the first trimester, an ultrasound examination should be performed.

In the rare instance when another antihypertensive agent cannot be used to treat the pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. Routine fetal testing with non-stress tests, biophysical profiles, and/or contraction stress tests may be appropriate based on gestational age and standards of care in the community. If oligohydramnios occurs in these situations, individualized decisions about continuing or discontinuing aliskiren-valsartan treatment and about pregnancy management should be made by the patient, her physician, and experts in the management of high risk pregnancy. Patients and physicians should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to aliskiren-valsartan should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, these infants may require blood pressure and renal perfusion support. Exchange transfusion or dialysis may be required to reverse hypotension or support decreased renal function.

No reproductive toxicology studies have been conducted with the combination of aliskiren and valsartan. However, these studies have been conducted for aliskiren as well as valsartan alone.

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