Pregnancy: US FDA Pregnancy Category D.
The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy. The use of AIIRAs is contraindicated during the second and third trimester of pregnancy (see CONTRAINDICATIONS).
Epidemiological evidence reported regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy is inconclusive, however, a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data reported on the risk with AIIRAs, similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be administered an alternative anti-hypertensive treatments with an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate therapy should be started.
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. AIIRAs therapy exposure during the second and third trimesters is reported to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia). Resulting oligohydramnios is reportedly associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Therefore, when pregnancy is detected, valsartan/AIIRA should be discontinued as soon as possible and, if appropriate, alternative therapy should be started.
If exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
If there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue valsartan, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Close observation of infants with histories of in utero exposure to valsartan for hypotension, oliguria, and hyperkalemia is recommended.
Lactation: It is not known whether valsartan is excreted in human milk. Valsartan was reported to be excreted in the milk of lactating rats; however, animal breast milk drug levels may not accurately reflect human breast milk levels. Since many drugs are excreted into human milk and have the potential to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue valsartan, based on the importance of the drug to the mother.
Fertility: Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses up to 200 mg/kg/day which is 6 times the maximum recommended human dose.