serpine) during the 4 to 5 day
MAVENCLAD treatment cycles. If this is not possible,
consider selection of alternative concomitant drugs with no or
minimal ENT1, CNT3, or BCRP transporter inhibiting
properties. If this is not possible, dose reduction to the
minimum mandatory dose of drugs containing these
compounds, separation in the timing of administration, and
careful patient monitoring is recommended.
7.6 Potent BCRP and P-gp Transporter Inducers
Clinical Impact Possible decrease in cladribine exposure if potent BCRP or
P-gp transporter inducers are co-administered.
Prevention or Management Consider a possible decrease in cladribine efficacy if potent
BCRP (e.g., corticosteroids) or P-gp (e.g., rifampicin, St.
John's Wort) transporter inducers are co-administered.
7.7 Hormonal Contraceptives
Clinical Impact It is currently unknown whether MAVENCLAD may reduce
the effectiveness of systemically acting hormonal
contraceptives.
Prevention or Management Women using systemically acting hormonal contraceptives
should add a barrier method during MAVENCLAD dosing
and for at least 4 weeks after the last dose in each treatment
course.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
MAVENCLAD is contraindicated in pregnant women and in females and males of reproductivepotential who do not plan to use effective contraception. There are no adequate data on thedevelopmental risk associated with use of MAVENCLAD in pregnant women. Cladribine wasembryolethal when administered to pregnant mice and produced malformations in mice andrabbits [see Data]. The observed developmental effects are consistent with the effects ofcladribine on DNA [see Contraindications (4) and Warnings and Precautions (5.2)].
In the U.S. general population, the estimated background risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Thebackground risk of major birth defects and miscarriage for the indicated population is unknown.
Data
Animal Data
When cladribine was administered intravenously (0, 0.5, 1.5, or 3 mg/kg/day) to pregnant miceduring the period of organogenesis, fetal growth retardation and malformations (includingexencephaly and cleft palate) and embryofetal death were observed at the highest dose tested. Anincrease in skeletal variations was observed at all but the lowest dose tested. There was noevidence of maternal toxicity.
When cladribine was administered intravenously (0, 0.3, 1, and 3 mg/kg/day) to pregnant rabbitsduring the period of organogenesis, fetal growth retardation and a high incidence of craniofacialand limb malformations were observed at the highest dose tested, in the absence of maternaltoxicity.
When cladribine was administered intravenously (0, 0.5, 1.5, or 3.0 mg/kg/day) to micethroughout pregnancy and lactation, skeletal anomalies and embryolethality were observed at allbut the lowest dose tested.
8.2 Lactation
Risk Summary
MAVENCLAD is contraindicated in breastfeeding women because of the potential for seriousadverse reactions in breastfed infants [see Contraindications (4) and Warnings and Precautions(5)].
Advise women not to breastfeed during dosing with MAVENCLAD and for 10 days afterthe last dose.
There are no data on the presence of cladribine in human milk, the effects on the breastfed infant,or the effects of the drug on milk production.
8.3 Females and Males of Repro |
