Cladribine should be administered under the supervision of a qualified health care provider experienced in the use of antineoplastic therapy.
Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent.
Treatment with cladribine oral tablets may increase the risk of malignancy. Cladribine oral tablets are 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 cladribine oral tablets on an individual patient basis. Follow standard cancer screening guidelines in patients treated with cladribine oral tablets.
Serious neurological toxicity (including irreversible paraparesis and quadriparesis) has been reported in patients who received cladribine by continuous infusion at high doses (4 to 9 times the recommended dose for hairy cell leukemia). Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard cladribine dosing regimens.
Acute nephrotoxicity has been observed with high doses of cladribine (4 to 9 times the recommended dose for hairy cell leukemia), especially when given concomitantly with other nephrotoxic agents/therapies.
Cladribine oral tablets are contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with cladribine oral tablets in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during cladribine oral tablets dosing and for 6 months after the last dose in each treatment course. Stop cladribine oral tablets if the patient becomes pregnant.
Acute myeloid leukemia (off-label use):
Acute myeloid leukemia (newly diagnosed), induction (off-label use): DAC regimen: IV: 5 mg/m2 over 3 hours on days 1 to 5 (in combination with daunorubicin and cytarabine); a second induction cycle may be administered if needed (Holowiecki 2012).
Acute myeloid leukemia (relapsed/refractory), induction (off-label use): CLAG or CLAG-M regimen: IV: 5 mg/m2/day over 2 hours for 5 days (in combination with cytarabine and filgrastim ± mitoxantrone); a second induction cycle may be administered if needed (Robak 2000; Wierzbowska 2008; Wrzesien-Kus 2003).
Hairy cell leukemia:
IV: 0.14 mg/kg/day over 2 hours for 5 days for 1 cycle (Grever 2017) or 0.1 mg/kg/day continuous infusion for 7 days for 1 cycle (Goodman 2003; Saven 1998) or 0.09 mg/kg/day continuous infusion for 7 days for 1 cycle (Cladribine labeling [Fresenius] August 2016) or 0.15 mg/kg/day over 2 hours on days 1 to 5 as a single course (in combination with concurrent or delayed rituximab) (Chihara 2020).
SUBQ (off-label route): 0.1 to 0.14 mg/kg/day for 5 days for 1 cycle (Grever 2017).
Mantle cell lymphoma (off-label use): IV: 5 mg/m2/day over 2 hours for 5 days every 4 weeks for 2 to 6 cycles (Inwards 2008) or 5 mg/m2/day over 2 hours for 5 days every 4 to 5 weeks for a maximum of 6 cycles (Rummel 1999) or 5 mg/m2/day over 2 hours for 5 days every 4 weeks for 2 to 6 cycles (in combination with rituximab) (Inwards 2008).
Multiple sclerosis, relapsing:
Note: Lymphocytes must be within normal limits before initiating first treatment course and ≥800 cells/mm3 before initiating the second treatment course. If needed, the second treatment course can be delayed up to 6 months to allow lymphocytes to recover to ≥800 cells/mm3. If lymphocytes <800 cells/mm3 after 6-month delay, do not continue cladribine. Screen for HIV, tuberculosis, and hepatitis B and C status prior to each treatment course. For patients who screen positive for latent infections, consult infectious disease or other appropriate specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]).
Oral: 3.5 mg/kg over 2-year treatment course, administered as 1.75 mg/kg in each year. Divide the 1.75 mg/kg dose over 2 cycles, each cycle lasting 4 to 5 consecutive days; do not administer more than 20 mg/day. In the first-year treatment course, initiate the first cycle at any time; administer the second cycle 23 to 27 days after the last dose of the first cycle. In the second-year treatment course, initiate the first cycle ≥43 weeks after the last dose of the first year's second cycle. Administer the second cycle 23 to 27 days after the last dose of the second year's first cycle. Following 2 years of treatment, do not administer oral cladribine during the next 2 years. Refer to manufacturer's labeling for additional dosing details, including dosing tables.
Missed doses: If a dose is not administered on a scheduled day, administer the missed dose on the following day and extend the number of days in that treatment cycle. If 2 consecutive doses are missed, extended the treatment cycle by 2 days.
T-cell large granular lymphocytic leukemia, refractory (off-label use; based on limited data): IV: 0.1 mg/kg/day continuous infusion for 7 days for 2 cycles (Edelman 1997).
Waldenström macroglobulinemia (off-label use):
IV: 0.1 mg/kg/day continuous infusion for 7 days every 4 weeks for 2 cycles (Dimopoulos 1994).
SUBQ: 0.1 mg/kg/day for 5 consecutive days every month for 4 cycles (in combination with rituximab) (Laszlo 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
IV: There are no dosage adjustments provided in the manufacturer's labeling (due to inadequate data); use with caution. The following adjustments have been recommended:
Krens 2019:
eGFR ≤50 mL/minute: Use is not recommended.
Hemodialysis: Use is not recommended.
Aronoff 2007:
CrCl 10 to 50 mL/minute: Administer 75% of dose.
CrCl <10 mL/minute: Administer 50% of dose.
Continuous ambulatory peritoneal dialysis (CAPD): Administer 50% of dose.
Oral:
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl <60 mL/minute: Use is not recommended.
IV: There are no dosage adjustments provided in the manufacturer's labeling (due to inadequate data); use with caution. The following adjustments have been recommended:
Mild impairment (Child-Pugh class A): Dosage adjustment is not likely necessary (Krens 2019).
Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended (Krens 2019).
Oral:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate to severe impairment (Child-Pugh classes B and C): Use is not recommended (has not been studied).
(For additional information see "Cladribine: Pediatric drug information")
Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
Acute myeloid leukemia: Limited data available: Infants, Children, and Adolescents: IV: 8.9 mg/m2/day continuous infusion for 5 days for 1 or 2 courses (Krance 2001) or 9 mg/m2/day over 30 minutes for 5 days for 1 course (in combination with cytarabine) (Crews 2002; Rubnitz 2009)
Langerhans cell histiocytosis, refractory: Limited data available: Infants, Children, and Adolescents: IV: 5 mg/m2/day over 2 hours for 5 days every 21 days for up to 6 cycles (Weitzman 2009); has also been administered as a continuous IV infusion: 5 mg/m2/day over 24 hours for 3 days; if tolerated, dose increased to 6.5 mg/m2/day over 24 hours for 3 days for subsequent courses (Stine 2004)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (due to inadequate data); use with caution. The following guidelines have been used by some clinicians (Aronoff 2007):
Infants, Children, and Adolescents: IV:
GFR >50 mL/minute/1.73 m2: No adjustment required.
GFR 10 to 50 mL/minute/1.73 m2: Administer 50% of dose.
GFR <10 mL/minute/1.73 m2: Administer 30% of dose.
Hemodialysis: Administer 30% of dose.
Continuous renal replacement therapy (CRRT): Administer 50% of dose.
There are no dosage adjustments provided in the manufacturer's labeling (due to inadequate data); use with caution.
Refer to adult dosing.
Hematology/Oncology uses: ASCO guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Generic: 10 mg/10 mL (10 mL)
Tablet Therapy Pack, Oral:
Mavenclad (10 Tabs): 10 mg [five packs containing 2 tablets ea] (10 ea)
Mavenclad (4 Tabs): 10 mg [four packs containing 1 tablet] (4 ea)
Mavenclad (5 Tabs): 10 mg [five packs containing 1 tablet] (5 ea)
Mavenclad (6 Tabs): 10 mg [one pack containing 2 tablets; four packs containing 1 tablet] (6 ea)
Mavenclad (7 Tabs): 10 mg [two packs containing 2 tablets ea; three packs containing 1 tablet ea] (7 ea)
Mavenclad (8 Tabs): 10 mg [three packs containing 2 tablets ea; two packs containing 1 tablet ea] (8 ea)
Mavenclad (9 Tabs): 10 mg [four packs containing 2 tablets ea; one pack containing 1 tablet] (9 ea)
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 mg/mL (10 mL, 20 mL); 10 mg/10 mL (10 mL)
Tablet Therapy Pack, Oral:
Mavenclad: 10 mg (1 ea, 4 ea, 5 ea, 6 ea, 7 ea, 8 ea)
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Mavenclad: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022561s006lbl.pdf#page=29
IV: Usually administered as a continuous infusion or over 2 hours; infusions over 3 hours have also been reported; refer to specific reference for infusion rate.
SUBQ (off-label route): May also be administered SUBQ (Grever 2017; Laszlo 2010).
Oral: Administer with water (with or without food); swallow whole immediately after removing from packaging; do not chew. Patients should use dry hands for handling and avoid prolonged contact with skin; wash hands and any surface that came in contact with the tablet thoroughly afterwards. Separate administration from any other oral medication by 3 hours. Refer to manufacturer's labeling for additional administration detail.
Parenteral: IV: Further dilute prior to use, may be administered over 24 hours as a continuous infusion, or as an intermittent infusion over 30 minutes or 2 hours; dependent upon indication and/or protocol.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Hairy cell leukemia (injection only): Treatment of active hairy cell leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.
Multiple sclerosis, relapsing (oral tablet only): Treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting (RRMS) and active secondary progressive disease in adults who have had inadequate response or are intolerant to other therapies for multiple sclerosis.
Limitations of use: Not recommended for patients with clinically isolated syndrome.
Acute myeloid leukemia; Mantle cell lymphoma; T-cell large granular lymphocytic leukemia (refractory); Waldenström macroglobulinemia
Cladribine may be confused with clevidipine, clofarabine, cytarabine, fludarabine
Leustatin may be confused with lovastatin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
IV:
>10%:
Hematologic & oncologic: Bone marrow depression (34%, may be delayed onset), febrile neutropenia (47%), severe anemia (37%), severe neutropenia (70%), thrombocytopenia (12%)
Infection: Bacterial infection (12%), infection (28%; serious infection: 6%)
Miscellaneous: Fever (69%; high fever: 11%)
1% to 10%: Infection: Fungal infection (6%), herpes zoster infection (4%), viral infection (6%)
Frequency not defined:
Cardiovascular: Edema, peripheral edema, phlebitis, tachycardia
Dermatologic: Ecchymosis, hyperhidrosis, pruritus, skin rash
Gastrointestinal: Abdominal pain, constipation, decreased appetite, diarrhea, flatulence, nausea, vomiting
Hematologic & oncologic: Bruise, decreased CD-4 cell count (nadir occurred 4 to 6 months following treatment and may continue to be depressed >15 months), petechia, purpuric disease
Infection: Bacteremia, localized infection, septicemia
Local: Bleeding at injection site, injection site reaction, localized edema
Nervous system: Anxiety, chills, dizziness, fatigue, headache, insomnia, malaise, myasthenia, pain, severe neurotoxicity
Neuromuscular & skeletal: Arthralgia, asthenia, myalgia
Respiratory: Abnormal breath sounds, cough, dyspnea, rales
Postmarketing:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, viral skin infection
Hematologic & oncologic: Tumor lysis syndrome
Nervous system: Progressive multifocal leukoencephalopathy
Respiratory: Pneumonia, respiratory tract infection
Oral:
>10%:
Hematologic & oncologic: Decreased hemoglobin (26%), decreased platelet count (11%), lymphocytopenia (24% to 87%)
Hypersensitivity: Hypersensitivity reaction (11%; severe hypersensitivity reaction: <1%)
Infection: Infection (49%)
Nervous system: Headache (25%)
Respiratory: Upper respiratory tract infection (38%)
1% to 10%:
Cardiovascular: Hypertension (5%)
Dermatologic: Alopecia (3%)
Gastrointestinal: Nausea (10%), oral herpes simplex infection (3%)
Hematologic & oncologic: Neutropenia (4%)
Infection: Herpes virus infection (6%), herpes zoster infection (2%)
Nervous system: Depression (5%), insomnia (6%)
Neuromuscular & skeletal: Arthralgia (≤7%), arthritis (≤7%), back pain (8%)
Respiratory: Bronchitis (5%)
Miscellaneous: Fever (5%)
<1%:
Cardiovascular: Cardiac failure, myocarditis
Hepatic: Hepatic injury
Nervous system: Seizure (tonic clonic), status epilepticus
Respiratory: Tuberculosis
Frequency not defined:
Dermatologic: Skin rash
Hematologic & oncologic: Malignant melanoma, malignant neoplasm, malignant neoplasm of ovary, pancreatic adenocarcinoma
Infection: Coccidioidomycosis, fungal infection
Renal: Pyelonephritis
Hypersensitivity to cladribine or any component of the formulation
Oral tablet: Current malignancy; pregnancy; men or women of reproductive potential who do not plan to use effective contraception during therapy and for 6 months after the last dose in each treatment course; HIV infection; active chronic infections (eg, hepatitis or tuberculosis); breastfeeding (during treatment or for 10 days after last dose)
Oral tablet [Canadian product]: Additional contraindications (not in US labeling): Increased risk of opportunistic infections (including those immunocompromised due to therapy [immunosuppressive or immunomodulating, antineoplastic or myelosuppressive therapies; total lymphoid irradiation; bone marrow transplantation] or disease [immunodeficiency syndrome]); history of progressive multifocal leukoencephalopathy; moderate or severe renal impairment (CrCL <60 mL/minute)
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Injection: Dose-dependent myelosuppression (neutropenia, anemia, and thrombocytopenia) is common and generally reversible. Lymphopenia has also been reported in patients receiving oral tablets for multiple sclerosis (MS). Use with caution in patients with preexisting hematologic or immunologic abnormalities and patients receiving other drugs that affect the hematologic profile concurrently or prior to treatment with cladribine. Monitor blood counts at baseline and during and after treatment.
• Cardiotoxicity: Cardiotoxicity, including life-threatening acute cardiac failure with myocarditis, has been reported.
• Fever: Treatment is associated with fever (≥100°F), with or without neutropenia, and is observed more commonly in the first month of treatment.
• Graft-versus-host disease: Graft-versus-host disease (GVHD) has been reported rarely in cladribine treated patients following transfusions of nonirradiated blood. Consult with a hematologist; irradiation of cellular blood components prior to transfusion is recommended.
• Hepatotoxicity: Serious liver injury or liver injury leading to treatment discontinuation has been reported within a few weeks to several months after initiation with cladribine. Monitor liver function. If patient develops unexplained liver enzyme elevations or symptoms of liver dysfunction, including abdominal pain, anorexia, dark urine, fatigue, jaundice, or unexplained nausea or vomiting, interrupt or discontinue treatment with cladribine.
• Hypersensitivity: Hypersensitivity reactions have occurred. Discontinue cladribine if a hypersensitivity reaction is suspected.
• Infection: Serious and potentially fatal infections (bacterial, viral, and fungal) have been reported. Due to neutropenia and T-cell depletion, risk versus benefit of treatment should be evaluated in patients with active infections. If active infection is present, manage appropriately prior to administering cladribine (Grever 2017). For the treatment of MS, screen for HIV, tuberculosis, and hepatitis B and C status prior to each treatment course. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). Consider interrupting or delaying oral cladribine treatment in patients with lymphocyte counts <500/mm3 and signs or symptoms of infections, including herpes infections. If lymphocyte counts <200 cells/mm3, administer anti-herpes prophylaxis. Initiating oral cladribine during concomitant treatment with immunosuppressive or myelosuppressive therapies is not recommended.
• Malignancy: [US Boxed Warning]: Oral tablet: Treatment with cladribine oral tablets may increase the risk of malignancy. After the completion of 2 courses of treatment, do not administer cladribine oral tablets for 2 years. Cladribine oral tablets are 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 cladribine oral tablets on an individual patient basis. Follow standard cancer screening guidelines in patients treated with cladribine oral tablets.
• Neurotoxicity: [US Boxed Warning]: Injection: Serious, dose-related neurologic toxicity (including irreversible paraparesis and quadriparesis) has been reported with continuous infusions of higher doses (4 to 9 times the approved dose); may also occur at approved doses (rare). Neurotoxicity may be delayed and may present as progressive, irreversible motor weakness of the upper and/or lower extremities; diagnostics with electromyography and nerve conduction studies were consistent with demyelinating disease. Neurotoxicity after high-dose administration was first noted 35 to 84 days after therapy initiation.
• Progressive multifocal leukoencephalopathy: Cases of progressive multifocal leukoencephalopathy (PML) due to the John Cunningham (JC) virus have been reported in patients receiving parenteral cladribine for oncologic indications. Symptoms progress over days to weeks and may include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, and mental status changes. Obtain baseline MRI before treatment initiation. At the first sign or symptom suggestive of PML, perform a diagnostic evaluation and withhold therapy. MRI findings may be apparent before patients are symptomatic. Monitoring with brain MRI for signs that may be consistent with PML may be beneficial and allow for an early diagnosis of PML.
• Renal toxicity: [US Boxed Warning]: Injection: Acute nephrotoxicity (eg, acidosis, anuria, increased serum creatinine), possibly requiring dialysis, has been reported with high doses (4 to 9 times the approved dose), particularly when administered with other nephrotoxic agents. Per the manufacturer, nephrotoxicity has not occurred when used at the dose approved for hairy cell leukemia.
• Tumor lysis syndrome: With high tumor burden, tumor lysis syndrome and subsequent hyperuricemia may occur (rare); consider antihyperuricemics and hydrate accordingly.
Special populations:
• Pregnancy: [US Boxed Warning]: Oral tablet:Cladribine oral tablets are contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with cladribine oral tablets in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during cladribine oral tablet dosing and for 6 months after the last dose in each treatment course. Stop cladribine oral tablets if the patient becomes pregnant.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Injection: Weekly (7-day) infusion preparation recommends further dilution with bacteriostatic normal saline which contains benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Experienced physician: [US Boxed Warning]: Injection: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Vaccines: When used in the oncology setting, administration of live-attenuated or live vaccines is not recommended during treatment with cladribine (may increase the risk of infection due to immunosuppression). When using for the treatment of MS, complete necessary immunizations at least 4 to 6 weeks prior to initiating cladribine. Avoid live-attenuated vaccines in patients who currently receive or have recently discontinued cladribine; consider using live-attenuated vaccines only if risk of infection is high and killed vaccines are unavailable (AAN [Farez 2019]). Provide VZV vaccination prior to initiation of therapy in VZV antibody–negative patients. In antibody-positive patients, vaccination with zoster vaccine (recombinant) is recommended any time prior to or during the course of treatment; may also administer if lymphocyte counts are ≤500 cells/mm3.
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Agents that Undergo Intracellular Phosphorylation: May diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
BCRP/ABCG2 Inducers: May decrease the serum concentration of Cladribine. Risk C: Monitor therapy
BCRP/ABCG2 Inhibitors: May increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Hormonal Contraceptives: Cladribine may diminish the therapeutic effect of Hormonal Contraceptives. Management: In females of reproductive potential using systemically acting hormonal contraceptives, add a barrier method during cladribine dosing and for at least 4 weeks after the last dose in each treatment course Risk D: Consider therapy modification
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins: May increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider therapy modification
Interferons (Beta): Cladribine may enhance the adverse/toxic effect of Interferons (Beta). Specifically, the risk for lymphopenia may be increased. Risk X: Avoid combination
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Methotrexate: May enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Myelosuppressive Agents: Cladribine may enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Cladribine. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Cladribine may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of cladribine when possible. Patients vaccinated less than 14 days before initiating or during cladribine should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Cladribine may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Cladribine may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Zoster Vaccine (Recombinant): Cladribine may diminish the therapeutic effect of Zoster Vaccine (Recombinant). Management: Vaccination with recombinant zoster vaccine is permitted for seropositive patients. Seronegative patients should be vaccinated prior to cladribine therapy. Consider revaccination 3 months after therapy for patients vaccinated during cladribine therapy. Risk D: Consider therapy modification
Females of reproductive potential should use highly effective contraception during therapy regardless of the route of administration/indication for treatment.
[US Boxed Warning]: Oral tablet: Cladribine is contraindicated for use in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Exclude pregnancy before the start of treatment with cladribine in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during cladribine dosing and for 6 months after the last dose in each treatment course. Pregnancy should be excluded in females of reproductive potential prior to each course of cladribine. The effect of cladribine on hormonal contraceptives is not known, use of a barrier method is recommended in addition to systemic hormonal contraceptives during therapy and for 4 weeks after the last cladribine dose.
In general, disease-modifying therapies for multiple sclerosis are stopped prior to a planned pregnancy except in females at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]). Consider use of agents other than cladribine for females at high risk of disease reactivation who are planning a pregnancy. Delaying pregnancy is recommended for females with persistent high disease activity; when disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to cladribine is expected to cause fetal harm.
[US Boxed Warning]: Oral tablet: Cladribine is contraindicated for use in pregnant women because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Stop cladribine if the patient becomes pregnant.
In general, disease-modifying therapies for multiple sclerosis are not initiated during pregnancy, except in females at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]).
Information related to the use of cladribine for the treatment of hairy cell leukemia in pregnancy is limited (Daver 2013).
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).
It is not known if cladribine is present in breast milk.
Use of the oral tablet is contraindicated in breastfeeding females during treatment and for 10 days after the last cladribine dose.
According to the manufacturer, due to the potential for serious adverse reactions in the breastfed infant, when using cladribine injection the decision to discontinue cladribine or to discontinue breastfeeding should take into account the importance of treatment to the mother. Some sources recommended withholding breastfeeding for at least 48 hours after the last cladribine injection, longer in patients with impaired renal function (Almas 2016).
IV: CBC with differential (at baseline, during, and after treatment; particularly during the first 4 to 8 weeks post-treatment), renal and hepatic function; bone marrow biopsy (after CBC has normalized, to confirm treatment response). Monitor for fever; monitor for signs/symptoms of neurotoxicity, infection, hepatotoxicity, progressive multifocal leukoencephalopathy (PML), and tumor lysis syndrome.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Oral tablet: CBC including lymphocyte count (before each treatment course, 2 and 6 months after the start of each yearly course [if 2-month lymphocyte <200 cells/mm3, monitor monthly until month 6], and periodically during and after treatment); evaluate HIV, tuberculosis, hepatitis B (HBV) and hepatitis C (HCV) status (prior to each treatment course); evaluate varicella zoster virus VZV antibody status (prior to treatment initiation); pregnancy test (prior to treatment in females of reproductive potential); liver function tests (serum aminotransferase, alkaline phosphatase and total bilirubin levels) (prior to each treatment course and as clinically appropriate); MRI (at baseline [within 3 months] prior to first treatment course); signs or symptoms of progressive multifocal leukoencephalopathy (if PML is suspected, obtain brain MRI scan); standard cancer screening; signs or symptoms of acute infection
Cladribine is a purine nucleoside analogue; it is a prodrug which is activated by phosphorylation and converted into the active moiety, Cd-ATP. This active form incorporates into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis and repair. This also results in a depletion of nicotinamide adenine dinucleotide and adenosine triphosphate (ATP). Cladribine is cell-cycle nonspecific. The mechanism of cladribine in treating multiple sclerosis (MS) is unknown, but may involve cytotoxic effects on B and T lymphocytes that result from the shutdown of DNA synthesis, leading to a depletion of lymphocytes.
Absorption: Oral: Rapid; delayed with food
Distribution: Vd:
Children 8 months to 18 years: 12.7 ± 8.5 L/kg; penetrates CSF (CSF concentrations are ~18% of plasma concentration) (Kearns 1994)
Adults: 480 to 490 L or ~9 L/kg; penetrates CSF (CSF concentrations are ~25% of plasma concentrations)
Protein binding: ~20%
Metabolism: Prodrug; activated via phosphorylation to active metabolite, Cd-ATP; negligible hepatic metabolism.
Bioavailability: Oral tablet: ~40%
Half-life elimination:
Children 8 months to 18 years: IV: 19.7 ± 3.4 hours (Kearns 1994)
Adults: IV: After a 2-hour infusion (with normal renal function): 5.4 hours; Oral: ~24 hours
Time to peak: Oral: Median 0.5 hour (range 0.5 to 1.5 hours) (fasting); 1.5 hours (range 1 to 3 hours) (with high-fat meal)
Excretion: Urine (18% to 28.5%)
Altered kidney function:
Mild impairment (CrCl 60 to 90 mL/minute): 18% decrease in total clearance; 25% increase in cladribine exposure
Moderate or serious impairment: Limited clinical experience.
Solution (Cladribine Intravenous)
10 mg/10 mL (per mL): $42.00 - $52.20
Tablet Therapy Pack (Mavenclad (10 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (4 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (5 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (6 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (7 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (8 Tabs) Oral)
10 mg (per each): $10,970.27
Tablet Therapy Pack (Mavenclad (9 Tabs) Oral)
10 mg (per each): $10,970.27
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