Names and pronunciation
(klad′-dri-been) Mavenclad
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Drug reference
(klad′-dri-been) Mavenclad
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Func. class.: Multiple sclerosis agent/ antineoplastic
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Chem. class.: Purine nucleoside antimetabolite
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ACTION: May be lymphocyte depletion through cytotoxic effects on B and T lym- phocytes through impairment of DNA syn- thesis
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USES: Relapsing multiple sclerosis, active hairy-cell leukemia
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CONTRAINDICATIONS: Breast- feeding, HIV, TB
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Black Box Warning: Pregnancy Precautions: Contraceptive requirements, hepatic dis- ease, infection, renal disease, progressive multifocal leukoencephalopathy, neonates, premature Black Box Warning: Bone marrow suppression, neurotoxicity, nephrotoxic- ity, new primary malignancy, reproductive risk; requires an experienced clinician Black Box Warning: Bone marrow suppression: assess for neutropenia, anemia, thrombocytopenia; usually re- versible and dose dependent; during the first 2 wk after treatment initiation, mean platelet count, absolute neutrophil count (ANC) and HB declined, and then increased by day 15, wk 5, and wk 8; monitor hematologic parameters espe- cially during the first 4 to 8 wk after treatment Black Box Warning: Secondary malig- nancies: monitor for secondary malig- nancies Black Box Warning: Pregnancy/ breastfeeding: assess if pregnancy is planned or suspected or if breastfeeding
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SIDE EFFECTS CNS: Fatigue, fever, headache, neurotoxicity HEMA: Anemia, neutropenia, thrombocyto- penia, lymphopenia GI: Nausea GU: Nephrotoxicity INTEG: Rash
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INTERACTIONS • Do not use with live virus vaccines • Duplicate effects: immunosuppres- sives, avoid using together • Antiviral and antiretroviral drugs: avoid concomitant use • BCRP or ENT/CNT inhibitors: may al- ter bioavailability; avoid using together
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DOSAGE AND ROUTES Relapsing forms of multiple sclerosis Adults: PO 1.75 mg/kg per treatment course divided into 2 cycles and given as divided doses of 1 or 2 tablets daily over 4 or 5 days for each cycle with second cycle starting 23 to 27 days after the last dose of first cycle; give a second course at least 43 wk after the last dose of the first course, second cycle for a cumulative dosage of 3.5 mg/kg; max: 20 mg (2 tablets)/cycle day Active hairy-cell leukemia (orphan drug) Adult: IV: 0.14 mg/kg/day over 2 hr for 5 days or 0.1 mg/kg/day continuous infu- sion for 7 days for 1 cycle or 0.09 mg/ C kg/day continuous infusion for 7 days for 1 cycle
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Available forms: Tablet 10 mg, solution for injection 1 mg/mL
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Administer: • Follow cytotoxic handling and disposal procedures • Separate all other products by ≥3 hr during the 4- or 5-day treatment cycles PO route • Use dry hands; wash hands after use; avoid prolonged contact with skin • If a tablet is left on a surface, broken or fragmented, wash the area with water • Take without regard to meals; swallow whole with water immediately after re- moval from blister; do not chew IV route • Visually inspect for particulate matter and discoloration prior to use; a precipi- tate may occur during the exposure of injection to low temperatures; it may be resolubilized by allowing the solution to warm to room temperature and by shak- ing vigorously • Does not contain preservative • The concentrate for injection must be diluted before use; do not use dextrose 5% injection, or benzyl alcohol in neo- nates; do not admix Daily IV infusion: • Add calculated daily dose of the con- centrate through a sterile 0.22-microm- eter disposable hydrophilic syringe filter to a polyvinyl chloride infusion bag con- taining 500 mL of 0.9% sodium chloride injection; discard any unused portion; vials are for single-use only; once solu- tions are diluted, administer or store at 35.6°F to 46.4°F (2°C to 8°C) for no more than 8 hr before the start of administration • Infuse over 24 hr • Admixtures are stable for at least 24 hr at room temperature under normal room fluorescent light in Baxter Viaflex PVC infusion containers Seven-day IV infusion: • Calculate the dose for a 7-day period and withdraw from the concentrate for injection; dilute in bacteriostatic 0.9% sodium chloride injection containing benzyl alcohol as a preservative; first the calculated 7-day dose and then the amount of diluent needed to bring the total volume to 100 mL should be passed through a sterile 0.22-micrometer dis- posable hydrophilic syringe filter as each solution is being added to the infusion reservoir; after completing solution preparation, clamp off the line, discon- nect, and discard the filter; aspirate air bubbles from the reservoir using the sy- ringe and a dry second sterile filter or a sterile vent filter assembly; reclamp the line, and discard the syringe and filter • Discard unused portion of injection; vials are for single-use only; once solutions are diluted, administer or store at 35.6°F to 46.4°F (2°C to 8°C) for no more than 8 hr before the start of administration • Infuse over 7 days
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Assess: • Progressive multifocal leukoen- cephalopathy (PML): Assess for new or worsening neurologic, cognitive, or be- havioral signs or symptoms, irreversible paraparesis and quadriparesis; may be more common in those who received continuous infusion at high doses (4 to 9 times the recommended dose for hairy cell leukemia)
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Evaluate: Therapeutic response: Decrease in spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • If a dose is missed, take the missed dose on the following day and extend the number of days in that treatment cycle; if 2 consecutive doses are missed, extend the treatment cycle by 2 days Black Box Warning: Pregnancy/ breastfeeding: advise females of repro- ductive potential to use effective contra- ception during treatment with PO product and for at least 6 mo after the last dose in each course; instruct women who are using systemic hormonal contraceptives to add a barrier method during PO product and for at least 4 wk after the last treat- ment; advise male patients of reproductive potential to take precautions to prevent pregnancy of their partner during PO treat- ment and for at least 6 mo after the last dose in each treatment course; highly effective contraception is recommended during treatment with IV product
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PHARMACOKINETICS Protein binding 20%; crosses blood- brain barrier; half-life 1 day; PO product effect is decreased by a high-fat meal
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