Indications for: MAVENCLAD
Relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease.
Limitations of Use:
Not for use in clinically isolated syndrome (CIS).
The efficacy of Mavenclad was evaluated in a 96-week randomized, double-blind, placebo-controlled clinical study (Study 1; NCT00213135) in 1326 patients with relapsing forms of MS who had at least 1 relapse in the previous 12 months. Patients were randomly assigned to receive either placebo (n=437) or a cumulative oral dosage of Mavenclad 3.5 mg/kg (n=433) or 5.25 mg/kg (n=456) for 96 weeks in 2 treatment courses.
The primary endpoint was the annulaized relapse rate (ARR). Additional outcome measures included the proportion of patients with confirmed disability progression, the time to first qualifying relapse, the mean number of MRI T1 Gadolinium-enhancing (Gd+) lesions, and new or enlarging MRI T2 hyperintense lesions.
Results showed that treatment with Mavenclad 3.5 mg/kg achieved the following clinical outcomes at week 96 compared with placebo, respectively:
ARR: 0.14 vs 0.33 (P <.001); relative reduction, 58%
Proportion of patients without relapse: 81% vs 63% (nominal P <.05)
Time to 3-month confirmed EDSS progression, Hazard Ratio: 0.67 (nominal P <.05)
Proportion of patients with a 3-month EDSS progression: 13% vs 19%
Median number of active T1 Gd+ lesions: 0 vs 0.33 (P <.001)
Median number of active T2 lesions: 0 vs 0.67 (P <.001)
See full labeling. Give 3.5mg/kg cumulative dose divided into 2 yearly treatment courses (1.75mg/kg per treatment course). ≥18yrs: Swallow whole. Each cycle: give 1–2 tabs once daily over 4–5 consecutive days. First course/first cycle: start at any time; first course/second cycle: give 23–27 days after the last dose of first course/first cycle. Second course/first cycle: give ≥43 weeks after the last dose of first course/second cycle; second course/second cycle: give 23–27 days after the last dose of second course/first cycle. 40–<50kg: 4 tabs per cycle; 50–<60kg: 5 tabs per cycle; 60–<70kg: 6 tabs per cycle; 70–<80kg: 7 tabs per cycle; 80–<90kg: 8 tabs in first cycle, then 7 tabs in second cycle; 90–<100kg: 9 tabs in first cycle, then 8 tabs in second cycle; 100–<110kg: 10 tabs in first cycle, then 9 tabs in second cycle; ≥110kg: 10 tabs per cycle. Give herpes prophylaxis if lymphocycte counts <200cells/mcL. Additional treatment after completion of 2 treatment courses: not recommended for next 2 years.
<18yrs: not recommended.
Current malignancy. Pregnancy. Men and women of reproductive potential (without plans to use effective contraception during and for 6 months after last dose in each course). Nursing mothers (who plan to breastfeed on treatment day and for 10 days after last dose). HIV infection. Active chronic infections (eg, hepatitis, TB).
Malignancies. Risk of teratogenicity.
Perform cancer screening according to guidelines prior to each course. Prior malignancy or increased risk of malignancy: evaluate benefits/risks. Risk of lymphopenia and hematologic toxicity; obtain CBC with differential (include lymphocyte counts) prior to, during, and after treatment. Exclude HIV infection prior to initiation. Screen for TB, hepatitis prior to first and second courses. Evaluate for acute infection; consider delaying start until fully controlled. Test for antibodies to varicella zoster virus; if negative, give vaccination prior to initiating cladribine; see full labeling. If lymphocyte counts <500cells/mcL: monitor for infections (eg, herpes) and treat. Administer all immunizations (except as noted for VZV) according to immunization guidelines prior to starting cladribine. Obtain baseline MRI (within 3 months) prior to first course due to risk of progressive multifocal leukoencephalopathy (PML); withhold and evaluate if signs/symptoms occur. Graft-versus-host disease with blood transfusion: irradiation of cellular blood component is recommended. Obtain serum AST/ALT, total bilirubin prior to first and second course. Interrupt or discontinue treatment if hepatic dysfunction is suspected. Cardiac failure. Moderate to severe renal or hepatic impairment: not recommended. Elderly. Risk of teratogenicity. Advise females and males (w. female partners) of reproductive potential to use effective contraception during and for ≥6 months after the last dose in each treatment course. Pregnancy: exclude status before initiation; discontinue if occurs during treatment. Nursing mothers: not recommended (during and for 10 days after the last dose).
Chlorinated purine nucleoside analog.
Concomitant myleosuppressive or other immunosuppressive therapy: not recommended. Give live-attenuated or live vaccines ≥4–6 weeks prior to treatment; avoid during and after treatment. Concomitant interferon-beta may increase lymphopenia risk: not recommended. Additive effects with hematotoxic drugs: monitor. Avoid concomitant drugs that require intracellular phosphorylation (eg, lamivudine, zalcitabine, ribavirin, stavudine, zidovudine). Avoid potent ENT1, CNT3, or BCRP transporter inhibitors (eg, ritonavir, eltrombopag, curcumin, cyclosporine, dilazep, nifedipine, nimodipine, cilostazol, sulindac, dipyridamole, reserpine) during the 4–5 day treatment cycles; if unavoidable, consider alternatives or reduce dose. May be antagonized by potent BCRP (eg, corticosteroids) or P-gp (eg, rifampicin, St John's wort) transporter inducers. Separate dosing with other oral drugs by ≥3hrs during the 4–5 day treatment cycles. Use additional barrier method with systemic hormonal contraceptives during and for ≥4 weeks after the last dose in each treatment course.
Upper respiratory tract infection, headache, lymphopenia, nausea, back pain, arthralgia/arthritis, insomnia, bronchitis, hypertension, fever, depression; liver injury, hypersensitivity (discontinue if occurs).
Renal. Half-life: ~1 day.
Generic Drug Availability:
Tabs—4, 5, 6, 7, 8, 9, 10