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Cladribine

Brand Name and Other Names: Mavenclad, Leustatin DSC

Generic Name: Cladribine

Drug Class: Purine Antimetabolite

What Is Cladribine Used For and How Does it Work?

Cladribine is used to treat relapsing-remitting forms of multiple sclerosis (MS) and active secondary progressive disease. Use of Cladribine is generally recommended for patients with inadequate response to, or unable to tolerate, an alternate indicated drug.

Off-label uses for Cladribine include for cutaneous T-cell lymphoma, ccute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), autoimmune hemolytic anemia, mycosis fungoides, and Sezary syndrome.

Cladribine is available under the following different brand and other names: Mavenclad and Leustatin DSC.

Dosages of Cladribine:

Dosage Forms and Strengths

Tablets

  • 10 mg (Mavenclad)

Injectable Solution (Generic Formulation)

  • 1mg/mL (10 mL single-use vial)

Dosage Considerations – Should be Given as Follows:

Relapsing Forms of Multiple Sclerosis

Cladribine only

  • Include relapsing-remitting disease and active secondary progressive disease
  • Use is generally recommended for patients with inadequate response to, or unable to tolerate, alternate indicated drug
  • 2 yearly treatment courses: 1.75 mg/kg/course orally; each course divided into 2 treatment cycles; not to exceed 3.5 mg/kg cumulative dosage (see oral administration)
  • Oral dose per cycle by weight in each treatment course
    • Also see Administration for timing of each treatment course and cycles
    • Less than 40 kg: Safety and efficacy not established
    • 40 kg to less than 50 kg: 40 mg first cycle; 40 mg second cycle
    • 50 kg to less than 60 kg: 50 mg first cycle; 50 mg second cycle
    • 60 kg to less than 70 kg: 60 mg first cycle; 60 mg second cycle
    • 70 kg to less than 80 kg: 70 mg first cycle; 70 mg second cycle
    • 80 kg to less than 90 kg: 80 mg first cycle; 70 mg second cycle
    • 90 kg to less than 100 kg: 90 mg first cycle; 80 mg second cycle
    • 100 kg to less than 110 kg: 100 mg first cycle; 90 mg second cycle
    • 110 kg or greater: 100 mg first cycle; 100 mg second cycle
    • Do not administer more than 2 tablets daily; administer 1-2 tablets/day orally over 4-5 consecutive days

Hairy Cell Leukemia

Cladribine (parenteral only)

  • 0.09 mg/kg/day intravenously (IV) continuous infusion for 7 days

Dosing considerations

  • Monitor complete blood count (CBC) with differential
  • Monitor for signs/symptoms of neurotoxicity and infection; if infection present, treat as appropriate prior to therapy; if not possible, consider alternative therapy if possible

Dosage Modifications

Cladribine only

  • Renal impairment
    • Mild (CrCl 60-89 mL/minute): No dosage adjustment recommended
    • Moderate to severe (CrCl less than 60 mL/minute): Not recommended
  • Hepatic impairment
    • Mild: No dosage adjustment recommended
    • Moderate to severe (Child-Pugh greater than 6): Not recommended

Dosing considerations

Cladribine only

  • Limitations of use: Treatment is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile
  • Prior to administration
  • Complete blood count
    • Lymphocytes must be within normal limits before initiating first treatment course and at least 800 cells/mcL before initiating second treatment course
    • May delay second treatment course for up to 6 months to allow for recovery of lymphocytes to at least 800 cells per microliter; if recovery takes more than 6 months, patient should not receive further treatment
    • Obtain CBC with differential including lymphocyte count before initiating first treatment course and before initiating second course
    • Obtain CBC with differential including lymphocyte count 2 and 6 months after start of treatment course; if lymphocyte count at month 2 less than 200 cells/mcL, monitor monthly until month 6 and periodically thereafter and when clinically indicated
    • Hold therapy if lymphocyte count less than 200 cells/mcL
    • Administer antiherpes prophylaxis in patients with lymphocyte counts less than 200 cells/mcL

Safety and efficacy not established in pediatric patients

Other Uses

Off-label: Cutaneous T-cell lymphoma, ccute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), autoimmune hemolytic anemia, mycosis fungoides, Sezary syndrome

QUESTION

What kind of disease is multiple sclerosis? See Answer

What Are Side Effects Associated with Using Cladribine?

Common side effects of cladribine include:

Cladribine

Cladribine (parenteral)

Less common side effects of Cladribine include:

Cladribine

  • Seizures

Cladribine (parenteral)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Cladribine?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Cladribine has no listed severe interactions with other drugs.

Serious interactions of Cladribine include:

  • adenovirus types 4 and 7 live, oral
  • palifermin
  • tofacitinib

Moderate interactions of Cladribine include:

Mild interactions of Cladribine include:

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Cladribine?

Warnings

This medication contains Cladribine. Do not take Mavneclad or Leustatin DSC if you are allergic to Cladribine or any ingredients contained in this drug.

Cladribine

  • Malignancies
    • Therapy may increase risk of malignancy
    • Contraindicated in patients with current malignancy
    • Evaluate on an individual patient basis the benefits and risks therapy in patients with prior malignancy or with increased risk of malignancy; follow standard cancer screening guidelines in patients receiving therapy
  • Risk of teratogenicity
    • Contraindicated for use in pregnant women and women and men of reproductive potential who do not plan to use effective contraception because of potential for fetal harm
    • Malformations and embryolethality shown in animals
    • Exclude pregnancy before start of treatment in females of reproductive potential
    • Advise females and males of reproductive potential to use effective contraception during therapy and for 6 months after last dose in each treatment course
    • Stop therapy if patient becomes pregnant

Cladribine (parenteral)

  • The drug should be administered under the supervision of an experienced cancer chemotherapy physician
  • Bone marrow suppression may occur but is usually reversible and appears to be dose dependent
  • Continuous infusion of high doses of 4 to 9 times the recommended dose for hairy cell leukemia has been associated with serious acute nephrotoxicity and neurological toxicity resulting in irreversible paraparesis and quadriparesis; standard cladribine dosing regimens have also been associated with severe neurological toxicity
  • Acute nephrotoxicity reported with high doses (4-9 times recommended dose for hairy cell leukemia), especially when used concomitantly with nephrotoxic agents

Contraindications

Cladribine

  • Patients with current malignancy
  • Pregnant women and women and men of reproductive potential who do not plan to use effective contraception during therapy and for 6 months after last dose in each treatment course
  • Patients with infected HIV
  • Active chronic infections (e.g., hepatitis, tuberculosis)
  • History of hypersensitivity to drug or excipients
  • Women intending to breastfeed on a treatment day and for 10 days after last dose

Cladribine (parenteral)

  • Hypersensitivity

Effects of Drug Abuse

  • No information available

Short-Term Effects

  • See "What Are Side Effects Associated with Using Cladribine?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Cladribine?"

Cautions

Cladribine

  • Treatment may increase risk of malignancies, including metastatic pancreatic carcinoma, malignant melanoma, and ovarian cancer
  • Serious cases of thrombocytopenia, neutropenia, and pancytopenia (some with documented bone marrow hypoplasia) requiring transfusion and granulocyte-colony stimulating factor treatment reported; monitor complete blood count (CBC)
  • Advise women of potential risk to a fetus during therapy and for 6 months after last dose in each treatment course
  • Latent tuberculosis infections may be activated with therapy; in patients with tuberculosis infection, delay initiation of treatment until infection adequately treated
  • Patients who are carriers of hepatitis B or C virus may be at risk of irreversible liver damage caused by virus reactivation; in patients with hepatitis infection, delay initiation of therapy until infection adequately treated
  • Incidence of herpes zoster reported to be higher during period of absolute lymphocyte count less than 500 cells/mcL per microliter; monitor for signs and symptoms suggestive of infections, including herpes infections in patients with lymphocyte counts less than 500 cells/mcL; if such signs and symptoms occur, initiate treatment as clinically indicated; consider interruption or delay of therapy until there is resolution of infection
  • In patients treated with parenteral cladribine for oncologic indications, cases of PML reported in the postmarketing setting; no cases reported in clinical studies of receiving therapy for MS
  • In patients who require blood transfusion, irradiation of cellular blood components recommended prior to administration to decrease risk of transfusion-related graft versus host disease; consultation with hematologist advised
  • Liver injury may occur; if a patient develops clinical signs, including unexplained liver enzyme elevations or symptoms suggestive of hepatic dysfunction, including unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice, and/or dark urine, promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment as appropriate
  • Not for use in patients with history of hypersensitivity; discontinue therapy if hypersensitivity reaction suspected
  • Cardiac failure with myocarditis reported with parenteral cladribine for indications other than MS; patients should seek medical advice if they experience symptoms of cardiac failure, including shortness of breath, rapid or irregular heartbeat, or swelling

Cladribine (parenteral)

  • As with other potent chemotherapeutic agents, monitoring of renal and hepatic function is also recommended, especially in patients with underlying kidney or liver dysfunction
  • Allopurinol and IV hydration recommended for patients with high tumor burden to prevent tumor lysis syndrome
  • May impair fertility; shown to suppress rapidly generating cells, including testicular cells
  • Fever with or without neutropenia is frequently observed during first month of treatment; given known myelosuppressive effects of therapy, practitioners should carefully evaluate risks and benefits of administering this drug to patients with active infections
  • Nephrotoxicity reported with high doses (4-9 times approved dose), especially when coadministered with other nephrotoxic drugs; manufacturer reports no nephrotoxicity at doses approved for hairy cell leukemia
  • Periodic assessment of peripheral blood counts, particularly during first 4-8 weeks post-treatment, recommended to detect development of anemia, neutropenia and thrombocytopenia and for early detection of any potential sequelae (e.g., infection or bleeding)

Drug interaction overview

  • Therapy causes dose-dependent reduction in lymphocyte count; additive hematological adverse reactions may be expected if therapy administered prior to or concomitantly with other drugs that affect the hematological profile
  • Initiation of therapy in patients currently receiving immunosuppressive or myelosuppressive therapy not recommended; concomitant use may increase risk of myelosuppression; acute short-term therapy with corticosteroids may be administered
  • Do not administer live virus vaccines; risk of infection in setting of immunosuppression
  • Lymphopenia risk may be increased when therapy coadministered with interferon-beta
  • Avoid coadministration of potent ENT1, CNT3, or BCRP transporter inhibitors (e.g., ritonavir, eltrombopag, curcumin, cyclosporine, diltiazem, nifedipine, nimodipine, cilostazol, sulindac, dipyridamole, or reserpine) during the 4- to 5-day treatment cycle; the bioavailability, intracellular distribution, and renal elimination of the drug may be altered
  • Consider a possible decrease in efficacy if potent BCRP (e.g., corticosteroids) or P-gp (e.g., rifampicin, St. John's wort) transporter inducers are coadministered
  • Women using systemically acting hormonal contraceptives should add a barrier method during therapy and for at least 4 weeks after last dose in each treatment course

Pregnancy and Lactation

Cladribine is 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 Cladribine therapy in pregnant women.

Females of reproductive potential should use of effective contraception during Cladribine therapy and for at least 6 months after last dose in each treatment course; add also a barrier method during therapy and for at least 4 weeks after last dose in each treatment course. Male patients of reproductive potential should take precautions to prevent pregnancy of their partner during Cladribine therapy and for at least 6 months after last dose in each treatment course.

Cladribine therapy is contraindicated in breastfeeding women because of the potential for serious adverse reactions in breastfed infants. Women are advised not to breastfeed during Cladribine therapy and for 10 days after last dose. There are no data on presence of Cladribine in human milk, the effects on breastfed infants, or on milk production.

SLIDESHOW

Multiple Sclerosis (MS) Symptoms and Treatment See Slideshow
Reviewed on 2/7/2020
References
https://reference.medscape.com/drug/mavenclad-cladribine-342213
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