Cladribine

⛔ FDA Black Box Warning

WARNING: MALIGNANCIES AND RISK OF TERATOGENICITY Malignancies Treatment with cladribine tablets may increase the risk of malignancy. Cladribine tablets are contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of cladribine tablets on an individual patient basis. Follow standard cancer screening guidelines in patients treated with cladribine tablets [see Contraindications (4) and Warnings and Precautions ( 5.1 )] . Risk of Teratogenicity Cladribine tablets are contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with cladribine tablets in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course. Stop cladribine tablets if the patient becomes pregnant [see Contraindications (4), Warnings and Precautions (5.2), and Use in Specific Populations (8.1, 8.3)] . WARNING: MALIGNANCIES and RISK OF TERATOGENICITY See full prescribing information for complete boxed warning. Malignancies Cladribine tablets may increase the risk of malignancy. Cladribine tablets are contraindicated in patients with current malignancy; evaluate the benefits and risks on an individual basis for patients with prior or increased risk of malignancy. ( 5.1 ) Risk of Teratogenicity Cladribine tablets are contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the risk of fetal harm. ( 5.2 )

Contraindications

4 CONTRAINDICATIONS Cladribine tablets are contraindicated: in patients with current malignancy [ see Warnings and Precautions (5.1) ] . in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course. May cause fetal harm [ see Warnings and Precautions (5.2) and Use in Specific Populations (8.1, 8.3 )]. in patients infected with the human immunodeficiency virus (HIV) [ see Warnings and Precautions (5.4) ]. in patients with active chronic infections (e.g., hepatitis or tuberculosis) [ see Warnings and Precautions (5.4) ]. in patients with a history of hypersensitivity to cladribine [ see Warnings and Precautions (5.8) ]. in women intending to breastfeed on a cladribine treatment day and for 10 days after the last dose [ see Use in Specific Populations (8.2) ]. Patients with current malignancy. (4) Pregnant women, and women and men of reproductive potential who do not plan to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course. (4, 8.3) HIV infection. (4) Active chronic infections (e.g., hepatitis or tuberculosis). (4) History of hypersensitivity to cladribine. (4, 5.8) Women intending to breastfeed on a cladribine treatment day and for 10 days after the last dose. (4, 8.2)

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Cladribine tablets are contraindicated in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception. There are no adequate data on the developmental risk associated with use of cladribine in pregnant women. Cladribine was embryolethal when administered to pregnant mice and produced malformations in mice and rabbits [ see Data ]. The observed developmental effects are consistent with the effects of cladribine 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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background 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 mice during the period of organogenesis, fetal growth retardation and malformations (including exencephaly and cleft palate) and embryofetal death were observed at the highest dose tested. An increase in skeletal variations was observed at all but the lowest dose tested. There was no evidence of maternal toxicity. When cladribine was administered intravenously (0, 0.3, 1, and 3 mg/kg/day) to pregnant rabbits during the period of organogenesis, fetal growth retardation and a high incidence of craniofacial and limb malformations were observed at the highest dose tested, in the absence of maternal toxicity. When cladribine was administered intravenously (0, 0.5, 1.5, or 3 mg/kg/day) to mice throughout pregnancy and lactation, skeletal anomalies and embryolethality were observed at all but the lowest dose tested.