Pregnancy: Risk summary: There are no adequate and well-controlled studies of Revolade in pregnant women to inform a drug-associated risk. In animal developmental and reproductive toxicology studies, oral administration of eltrombopag to pregnant rats and rabbits throughout organogenesis resulted in developmental toxicity in rats (see Animal data as follows). The effect of eltrombopag on human pregnancy is unknown. Pregnant women or women of childbearing potential should be advised of the potential risk of Revolade to a fetus. Revolade should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.
Animal data: In embryo-fetal developmental toxicity studies in rats and rabbits, oral eltrombopag was administered to pregnant animals during organogenesis. In rats, a maternally toxic dose of 60 mg/kg/day (6 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 3 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day) resulted in decreased fetal weights and a slight increase in the incidence of the fetal variation, cervical rib. No evidence of major structural malformations was observed. In rabbits, there was no evidence of embryo-fetal toxicity or teratogenicity up to 150 mg/kg/day (0.5 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day).
In a pre-and postnatal developmental toxicity study in pregnant rats, oral eltrombopag was administered from gestation day 6 through lactation Day 20. No adverse effects on maternal reproductive function or on the development of the offspring were observed at doses up to 20 mg/kg/day (2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and similar to the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Eltrombopag was detected in the plasma of offspring. The plasma concentrations in pups increased with dose following administration of drug to the F0 dams.
Lactation: Risk summary: There is no information regarding the presence of eltrombopag or its metabolites in human milk, or their effects on the breastfed infant, or on milk production. However, eltrombopag was detected in the pups of lactating rats 10 days postpartum suggesting the potential for transfer during lactation. A decision must be made whether to discontinue breastfeeding or to continue/abstain from Revolade therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Females and males of reproductive potential: Contraception: Based on animal reproduction studies, Revolade can cause fetal harm when administered to a pregnant woman (see PREGNANCY as previously mentioned). Sexually-active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) when using Revolade during treatment and for at least 7 days after stopping treatment with Revolade.
Infertility: There is no effect of Revolade on fertility based on animal studies (see Pharmacology: Toxicology: NON-CLINICAL SAFETY DATA under Actions). Eltrombopag did not affect female or male fertility in rats at doses 2 and 3 times respectively the human clinical exposure based on AUC in patients with ITP at 75 mg/day and in patients with chronic Hepatitis C at 100 mg/day (see Pharmacology: Toxicology: NON-CLINICAL SAFETY DATA under Actions).