Livmarli Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Maternal use at the recommended clinical dose of LIVMARLI is not expected to result in measurable fetal exposure because systemic absorption following oral administration is low [see Pharmacology: Pharmacokinetics under Actions]. Maralixibat may inhibit the absorption of fat-soluble vitamins [see Clinical Considerations as follows; Fat Soluble Vitamin (FSV) Deficiency under Precautions]. In animal reproduction studies, no developmental effects were observed (see Data as follows).
The estimated background risk of major birth defects for the indicated population is higher than the general population because Alagille syndrome is an autosomal dominant condition. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations: Fetal/Neonatal Adverse Reactions: Maralixibat may inhibit the absorption of fat-soluble vitamins (FSV). Monitor for FSV deficiency and supplement as needed. Increased supplementation of FSVs may be needed during pregnancy [see Fat Soluble Vitamin (FSV) Deficiency under Precautions].
Data: Animal Data: No effects on embryo-fetal development were observed in pregnant rats treated orally with up to 1000 mg/kg/day (approximately 3300 to 12000 times the maximum recommended dose based on AUC [area under the plasma concentration-time curve]) or in pregnant rabbits treated orally with up to 250 mg/kg/day (approximately 1200 to 4700 times the maximum recommended dose based on AUC) during the period of organogenesis. No effects on postnatal development were observed in a pre- and postnatal development study, in which female rats were treated orally with up to 750 mg/kg/day during organogenesis through lactation. Maternal systemic exposure to maralixibat at the maximum dose tested was approximately 2500 to 9400 times the maximum recommended dose based on AUC.
Lactation: Risk Summary: LIVMARLI has low absorption following oral administration, and breastfeeding is not expected to result in exposure of the infant to LIVMARLI at the recommended dose [see Pharmacology: Pharmacokinetics under Actions]. There are no data on the presence of LIVMARLI in human milk, the effects on the breastfed infant, or the effects on milk production. Patients with ALGS can have FSV deficiency as part of their disease. Maralixibat may reduce absorption of fat-soluble vitamins [see Fat Soluble Vitamin (FSV) Deficiency under Precautions]. Monitor FSV levels and supplement FSV intake, if FSV deficiency is observed during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's need for LIVMARLI and any potential adverse effects on the breastfed child from LIVMARLI or from the underlying maternal condition.