Cladribine

MAVENCLAD is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Limitations of Use MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile. MAVENCLAD is a purine antimetabolite indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults.

The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes.

Assessments are required prior to starting each MAVENCLAD treatment course. 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. MAVENCLAD is a cytotoxic drug. Separate administration from any other oral drug by at least 3 hours.

MAVENCLAD is contraindicated: in patients with current malignancy. in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course for females, and 14 weeks for males. May cause fetal harm. in patients infected with the human immunodeficiency virus (HIV ). in patients with active chronic infections (e.g., hepatitis or tuberculosis). in patients with a history of hypersensitivity to cladribine. in females intending to breastfeed on a MAVENCLAD treatment day and for 10 days after the last dose. Patients with current malignancy.

Boxed warning (malignancies and risk of teratogenicity): Malignancies Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is 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 MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD. Lymphopenia: Monitor lymphocyte counts before, during and after treatment. Infections: Serious, including life-threatening and fatal infections, have occurred. Screen patients for active and latent infections, delay treatment until infection is fully resolved or controlled. Vaccination of patients seronegative to varicella zoster virus (VZV) is recommended prior to treatment.

The following serious adverse reactions and potential risks are discussed, or discussed in greater detail, in other sections of the labeling: Malignancies Risk of Teratogenicity Lymphopenia Infections Hematologic Toxicity Graft-Versus-Host Disease With Blood Transfusion Liver Injury Hypersensitivity Cardiac Failure Most common adverse reactions (incidence > 20%) are upper respiratory tract infection, headache, and lymphopenia.

Table 3 Drug Interactions with MAVENCLAD Immunomodulatory, Immunosuppressive, or Myelosuppressive Drugs Clinical Impact Concomitant use of MAVENCLAD with immunomodulatory, immunosuppressive, or myelosuppressive drugs may increase the risk of adverse reactions because of the additive effects on the immune system. Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short- term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of MAVENCLAD.

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store in original package in order to protect from moisture.