Cladribine

2 DOSAGE AND ADMINISTRATION Assessments are required prior to starting each cladribine treatment course. (2.1) Cumulative dosage of 3.5 mg/kg administered orally and divided into 2 treatment courses (1.75 mg/kg per treatment course). Each treatment course is divided into 2 treatment cycles. (2.2) Cladribine tablets are a cytotoxic drug. (2.4) Separate administration from any other oral drug by at least 3 hours. (2.4) 2.1 Assessments Prior to Starting Each Cladribine Treatment Course Cancer Screening Follow standard cancer screening guidelines because of the risk of malignancies [ see Boxed Warning and Warnings and Precautions (5.1) ]. Pregnancy Exclude pregnancy prior to treatment with cladribine tablets in females of reproductive potential [ see Contraindications (4) , Warnings and Precautions (5.2) , and Use in Specific Populations (8.1, 8.3) ]. Complete Blood Count (CBC) Obtain a CBC with differential including lymphocyte count [ see Dosage and Administration (2.5) and Warnings and Precautions (5.3) ]. Lymphocytes must be: within normal limits before initiating the first treatment course at least 800 cells per microliter before initiating the second treatment course If necessary, delay the second treatment course for up to 6 months to allow for recovery of lymphocytes to at least 800 cells per microliter. If this recovery takes more than 6 months, the patient should not receive further treatment with cladribine tablets. Infections [ see Warnings and Precautions (5.4) ] Exclude HIV infection. Perform tuberculosis screening. Screen for hepatitis B and C. Evaluate for acute infection. Consider a delay in cladribine treatment until any acute infection is fully controlled. Vaccination of patients who are seronegative for VZV is recommended prior to initiation of cladribine tablets. Vaccination of patients who are seropositive to VZV is recommended with zoster vaccine recombinant, adjuvanted. Patients may be administered zoster vaccine recombinant, adjuvanted at any time prior to or during the year 1 or year 2 course of cladribine treatment. These patients may also be administered the vaccine if their lymphocyte counts are ≤ 500 cells per microliter. Administer all immunizations (except as noted for VZV) according to immunization guidelines prior to starting cladribine tablets. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting cladribine tablets. Obtain a baseline (within 3 months) magnetic resonance imaging prior to the first treatment course because of the risk of progressive multifocal leukoencephalopathy (PML). Liver Injury Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to each treatment cycle and course [ see Warnings and Precautions (5.7) ]. 2.2 Recommended Dosage The recommended cumulative dosage of cladribine tablets is 3.5 mg per kg body weight administered orally and divided into 2 yearly treatment courses (1.75 mg per kg per treatment course) (see Table 1). Each treatment course is divided into 2 treatment cycles: Administration of First Treatment Course First Course/First Cycle: start any time. First Course/Second Cycle: administer 23 to 27 days after the last dose of First Course/First Cycle. Administration of Second Treatment Course Second Course/First Cycle: administer at least 43 weeks after the last dose of First Course/Second Cycle. Second Course/Second Cycle: administer 23 to 27 days after the last dose of Second Course/First Cycle. Table 1 Dose of Cladribine tablets per Cycle by Patient Weight in Each Treatment Course Weight Range Dose in mg (Number of 10 mg Tablets) per Cycle kg First Cycle Second Cycle 40* to less than 50 40 mg (4 tablets) 40 mg (4 tablets) 50 to less than 60 50 mg (5 tablets) 50 mg (5 tablets) 60 to less than 70 60 mg (6 tablets) 60 mg (6 tablets) 70 to less than 80 70 mg (7 tablets) 70 mg (7 tablets) 80 to less than 90 80 mg (8 tablets) 70 mg (7 tablets) 90 to less than 100 90 mg (9 tablets) 80 mg (8 tablets) 100 to less than 110 100 mg (10 tablets) 90 mg (9 tablets) 110 and above 100 mg (10 tablets) 100 mg (10 tablets) *The use of cladribine tablets in patients weighing less than 40 kg has not been investigated. Administer the cycle dosage as 1 or 2 tablets once daily over 4 or 5 consecutive days [ see How Supplied/Storage and Handling (16.1) ]. Do not administer more than 2 tablets daily. Following the administration of 2 treatment courses, do not administer additional cladribine treatment during the next 2 years. Treatment during these 2 years may further increase the risk of malignancy [ see Warnings and Precautions (5.1) ]. The safety and efficacy of reinitiating cladribine tablets more than 2 years after completing 2 treatment courses has not been studied. 2.3 Missed Dose If a dose is missed, patients should not take double or extra doses. If a dose is not taken on the scheduled day, then the patient must take the missed dose on the following day and extend the number of days in that treatment cycle. If two consecutive doses are missed, the treatment cycle is extended by 2 days. 2.4 Administration Cladribine tablets are taken orally, with water, and swallowed whole without chewing. Cladribine tablets can be taken with or without food. Separate administration of cladribine tablets and any other oral drugs by at least 3 hours during the 4 to 5 day cladribine treatment cycles [ see Clinical Pharmacology (12.6) ]. Cladribine tablets are a cytotoxic drug. Follow applicable special handling and disposal procedures [ see References (15) ]. Cladribine tablets are an uncoated tablet and must be swallowed immediately once removed from the blister. If a tablet is left on a surface, or if a broken or fragmented tablet is released from the blister, the area must be thoroughly washed with water. The patient’s hands must be dry when handling the tablets and washed thoroughly afterwards. Avoid prolonged contact with skin. 2.5 Laboratory Testing and Monitoring to Assess Safety Cancer Screening Follow standard cancer screening guidelines in patients treated with cladribine tablets [see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.1 )]. Complete Blood Count Obtain complete blood count (CBC) with differential including lymphocyte count: before initiating the first treatment course of cladribine tablets before initiating the second treatment course of cladribine tablets 2 and 6 months after start of treatment in each treatment course; if the lymphocyte count at month 2 is below 200 cells per microliter, monitor monthly until month 6. See Warnings and Precautions ( 5.3, 5.4 ) for instructions based on the patient’s lymphocyte counts and clinical status (e.g., infections). Hold cladribine tablets therapy if the lymphocyte count is below 200 cells per microliter periodically thereafter and when clinically indicated [ see Warnings and Precautions (5.5) ] 2.6 Recommended Concomitant Medication Herpes Prophylaxis Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter [ see Warnings and Precautions (5.4) ].

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1 INDICATIONS AND USAGE Cladribine tablets are indicated for the treatment of relapsing form of multiple sclerosis (MS), to include relapsing-remitting disease in adults.