Is Invega (paliperidone) safe to use during pregnancy?

Invega (Paliperidone) Safety in Pregnancy

Invega is not contraindicated during pregnancy, but should be used only when the benefits clearly justify the potential risks, particularly given the lack of robust human safety data and the known risk of neonatal extrapyramidal and withdrawal symptoms with third-trimester exposure. 1

FDA Classification and Risk Assessment

• Paliperidone does not have a formal FDA pregnancy category assignment under the current labeling system, but available data suggest it would fall under the former Category C classification (animal studies show adverse effects, inadequate human studies) 1

• The FDA drug label explicitly states that "overall, available data from published epidemiologic studies of pregnant women exposed to paliperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes" 1

• However, this absence of established risk reflects limited data rather than proven safety 1

Critical Neonatal Risks

Neonates exposed to antipsychotic drugs, including paliperidone, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery. 1

• These symptoms include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders 1

• Symptom severity varies considerably—some neonates recover within hours to days without treatment, while others require prolonged hospitalization 1

• All neonates exposed to paliperidone in the third trimester must be monitored for extrapyramidal and withdrawal symptoms and managed appropriately 1

Maternal Disease Considerations

• There is substantial risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide 1

• Untreated schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth, though it remains unclear whether this results directly from the illness or comorbid factors 1

• The decision to use paliperidone must weigh the maternal risk of untreated psychotic illness against potential fetal risks 1

Available Human Data

• A retrospective cohort study of 9,258 women exposed to antipsychotics during pregnancy showed no overall increased risk for major birth defects 1

• There was a small increase in risk of major birth defects (RR=1.26,95% CI 1.02-1.56) and cardiac malformations (RR=1.26,95% CI 0.88-1.81), though these findings were not specific to paliperidone 1

• A prospective observational study of 6 women treated with risperidone (paliperidone's parent compound) demonstrated placental passage of both risperidone and paliperidone 1

• One case report documented safe use of paliperidone palmitate throughout gestation in a 34-year-old patient with schizoaffective disorder, with no malformations or perinatal complications 2

• Pharmacokinetic modeling suggests that serum concentrations of paliperidone decrease during pregnancy due to CYP2D6 activity changes and recover abruptly after delivery, necessitating close monitoring 3

Clinical Management Algorithm

If paliperidone is deemed necessary during pregnancy:

1. First trimester: Avoid if possible, as this is the period of organogenesis when risk of congenital malformations is highest 4

2. Second and third trimesters: May continue if maternal benefit outweighs fetal risk, with awareness of third-trimester neonatal complications 1

3. Dosing adjustments: Monitor clinical response closely, as pregnancy-induced physiological changes may decrease drug concentrations 3

4. Delivery planning: Prepare neonatal care team for potential extrapyramidal or withdrawal symptoms requiring monitoring and possible intervention 1

5. Postpartum: Expect abrupt recovery of pre-pregnancy drug levels after delivery; monitor for maternal side effects and adjust dose if needed 3

Pregnancy Registry

• Healthcare providers are strongly encouraged to register patients exposed to paliperidone during pregnancy with the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388 or http://womensmentalhealth.org/clinical-andresearch-programs/pregnancyregistry/) 1

• This registry helps collect observational data to better assess risks for both new and established drugs 5

Common Pitfalls to Avoid

• Do not discontinue paliperidone abruptly in a pregnant woman with severe psychiatric illness without careful risk-benefit assessment, as maternal decompensation poses significant risks 1

• Do not assume safety based on absence of reported problems—the limited human data reflects insufficient study rather than proven safety 6

• Do not fail to prepare the neonatal team for potential complications in third-trimester exposures 1

• Do not use atenolol as an alternative if switching to a different medication class is considered, as it has documented fetal risks 4