Pregnancy: Risk Summary: There are no adequate data on the developmental risk associated with the use of BONSPRI in pregnant women. Ofatumumab may cross the placenta and cause fetal B-cell depletion based on findings from animal studies (see Data as follows).
Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to BONSPRI have not been studied in clinical trials. The potential duration of B-cell depletion in infants exposed to ofatumumab in utero, and the impact of B-cell depletion on the safety and effectiveness of vaccines, are unknown. Avoid administering live vaccines to neonates and infants exposed to BONSPRI in utero until B-cell recovery occurs [see Injection-Related Reactions under Precautions and Pharmacology: Pharmacodynamics under Actions].
Following administration of ofatumumab to pregnant monkeys, increased mortality, depletion of B-cell populations, and impaired immune function were observed in the offspring, in the absence of maternal toxicity, at plasma levels substantially higher than that in humans (see Data as follows).
Epidemiologic studies from USA, Canada, major EU countries and South American countries have shown that the risk of birth defects in MS population is similar to that in the general population. For spontaneous abortions and still births, the background risk in the MS population in the US appears to be similar to that in the general US population.
Data: Animal Data: Intravenous administration of ofatumumab (weekly doses of 0, 20, or 100 mg/kg) to pregnant monkeys during the period of organogenesis (gestations days 20 to 50) resulted in no adverse effects on embryofetal development; however, B-cell depletion was observed in fetuses at both doses when assessed on gestation day 100. Plasma exposure (Cave) at the no-effect dose (100 mg/kg) for adverse effects on embryofetal development was greater than 5000 times that in humans at the recommended human maintenance dose of 20 mg. A no-effect dose for effects on B-cells was not identified; plasma exposure (Cave) at the low-effect dose (20 mg/kg) was approximately 780 times that in humans at the recommended human maintenance dose (RHMD) of 20 mg/month.
Intravenous administration of ofatumumab (5 weekly doses of 0, 10, and 100 mg/kg, followed by biweekly doses of 0, 3, and 20 mg/kg) to pregnant monkeys throughout pregnancy resulted in no adverse effects on the development of the offspring. However, postnatal death, B-cell depletion, and impaired immune function were observed in the offspring at the high dose. The deaths at the high dose were considered secondary to B-cell depletion. Plasma exposure (Cave) in dams at the no-effect dose (100/20 mg/kg) for adverse developmental effects was approximately 500 times that in humans at RHMD. A no-effect level for mortality and immune effects in offspring was not established because of the limited number of evaluable offspring at the low dose.
Lactation: Risk Summary: There are no data on the presence of ofatumumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Human IgG is excreted in human milk, and the potential for absorption of ofatumumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BONSPRI and any potential adverse effects on the breastfed infant from BONSPRI or from the underlying maternal condition.
Females and Males of Reproductive Potential: Contraception: Females of childbearing potential should use effective contraception while receiving BONSPRI and for 6 months after the last treatment of BONSPRI [see Fetal Risk under Precautions and Pharmacology: Pharmacokinetics under Actions].