Mavenclad Use In Pregnancy & Lactation

Effects on Fertility: The effect of cladribine on human fertility is unknown.
In male mice, cladribine did not affect fertility at subcutaneous doses up to 30 mg/kg per day, but reduced testes weights and increased numbers of non-motile sperm were seen, indicating the presence of testicular effects. For these effects, 5 mg/kg per day was the no-observed-adverse-effect level (NOAEL).
In female mice, cladribine did not affect fertility up to a subcutaneous dose of 8 mg/kg per day (higher doses were not tested). The extrapolated daily exposure data (based on plasma AUC) associated with these dose levels in mice exceeded the daily exposure with the oral human dose in MS by at least an order of magnitude.
A 1-year subcutaneous study in monkeys reported testicular degeneration, prostatic inflammation, prostatic and seminal vesicle secretion depletion, epididymal hypospermia and increased incidence of degenerated cells, while a 3-month oral and subcutaneous study noted only reduced sperm motility. The estimated exposure (plasma AUC) at the no-effect oral dose (3 mg/kg/day) was 3-fold clinical MS exposure.
Male Patients: As cladribine interferes with DNA synthesis, adverse effects on human gametogenesis could be expected. Therefore, male patients must take precautions to prevent pregnancy of their partner during MAVENCLAD treatment and for at least 6 months after the last dose. This will allow time for completion of new male reproductive cycles to clear intracellular phosphorylated cladribine from the body.
If the partner of a male patient becomes pregnant during a course of his MAVENCLAD therapy, it is recommended that the partner be informed about the potential hazard to the foetus.
Use in Pregnancy: While there were no effects on female fertility, reproductive function or general performance of offspring, cladribine was shown to be embryolethal in pregnant mice, and the compound was teratogenic in mice and rabbits. A significant increase in foetal variations was observed in mice receiving 1.5 mg/kg/day or greater intravenously during the period of organogenesis, or from early gestation to weaning, and increased resorptions, reduced litter size and increased foetal malformations were observed in mice receiving 3 mg/kg/day. Foetal malformations were observed in rabbits that received 3 mg/kg/day intravenously during the period of organogenesis. The observed embryolethal and teratogenic effects are consistent with the pharmacological mechanisms of cladribine.
There are no adequate or well-controlled studies in human pregnancies. A limited amount of data is available from pregnant women exposed to MAVENCLAD prior to conception. No imbalance of adverse pregnancy outcomes between cladribine and placebo has been observed.
Although clinical data from MAVENCLAD did not reveal evidence of teratogenicity in humans, MAVENCLAD has been shown to inhibit DNA synthesis. Other agents that inhibit DNA synthesis (e.g. methotrexate) have been reported to be teratogenic in humans.
MAVENCLAD is contraindicated in pregnant women (refer to Contraindications).
Contraception: In women of childbearing potential, pregnancy must be excluded before the initiation of MAVENCLAD therapy in year 1 and year 2, and prevented by use of reliable contraception during MAVENCLAD treatment and for at least 6 months (6 menstrual cycles) after the last dose. This will allow for the removal of any follicle that may have been exposed to cladribine during or immediately after a course of treatment. Women using systemically acting hormonal contraceptives should add a barrier method during MAVENCLAD treatment and for at least 4 weeks after the last dose in each treatment year (refer to Interactions). Women who become pregnant during therapy with MAVENCLAD tablets should discontinue treatment.
In case of exposure to MAVENCLAD during pregnancy, it is recommended that the patient be informed about the potential hazard to the foetus.
Use in Lactation: It is not known whether cladribine is excreted in human milk. Because many medicines are excreted in human milk and the potential for serious adverse reactions in breast-fed infants from MAVENCLAD, a decision should be made either to discontinue breast-feeding or to discontinue MAVENCLAD, taking into account the importance of MAVENCLAD to the mother (refer to Contraindications).