Pregnancy: The safety of intramuscularly-injected paliperidone palmitate or orally-dose paliperidone for use during human pregnancy has not been established.
A retrospective observational cohort study based on a US claims database compared the risk of congenital malformations for live births among women with and without antipsychotic use during the first trimester of pregnancy. Paliperidone, the active metabolite of risperidone, was not specifically evaluated in this study. The risk of congenital malformations with risperidone, after adjusting for confounder variables available in the database, was elevated compared to no antipsychotic exposure (relative risk=1.26, 95% CI: 1.02-1.56). No biological mechanism has been identified to explain these findings and teratogenic have not been observed in non-clinical studies. Based on the findings of this single observational study, a causal relationship between in utero exposure to risperidone and congenital malformations has not been established.
No teratogenic effect was noted in any animal study. Laboratory animals treated with a high dose of oral paliperidone showed a slight increase in fetal deaths. Pregnancy parameters were not affected in rats given the intramuscular injection of the 1-month paliperidone palmitate injectable product. The high doses were toxic to the mothers. The offspring was not affected at oral exposures 20- to 22-fold the maximum human dose of oral paliperidone or at intramuscular exposures 6-fold the maximum human dose of the 1-month paliperidone palmitate injectable product.
Neonates exposed to antipsychotic drugs (including paliperidone) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in severity following delivery. These symptoms in the neonates may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Since paliperidone has been detected in plasma up to 18 months after a single-dose administration of INVEGA TRINZA, consideration should be given to the long-acting nature of INVEGA TRINZA as neonates may be at risk from INVEGA TRINZA administration before pregnancy or during first and second trimesters as well.
INVEGA TRINZA should only be used during pregnancy if the benefits outweigh the risks. The effect of INVEGA TRINZA on labor and delivery in humans is unknown.
Breast-feeding: In animal studies with paliperidone and in human studies with risperidone, paliperidone was excreted in the milk. Therefore, women receiving INVEGA TRINZA should not breast-feed infants. Since paliperidone has been detected in plasma up to 18 months after a single-dose administration of INVEGA TRINZA, consideration should be given to the long-acting nature of INVEGA TRINZA as nursing infants may be at risk even from INVEGA TRINZA administration long before nursing.