Version July 2025
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.
Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
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 (Ref); 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 (Ref)
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 (Ref):
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.
(For additional information see "Cladribine: Drug information")
Dosage guidance:
Safety: For oncologic uses, assess risk for tumor lysis syndrome; consider antihyperuricemics and hydrate accordingly.
Dosing: Cladribine may be dosed in mg/kg or in mg/m2; use caution with dose calculations.
Clinical considerations: Prophylactic anti-infectives should be considered for patients with an increased risk for developing opportunistic infections.
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 (Ref).
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 (Ref).
Erdheim-Chester disease (off-label use): IV: 0.14 mg/kg on days 1 to 5 every 28 days or 5 mg/m2 on days 1 to 5 every 28 days; the median number of cycles administered was 2.5 (range: 1 to 6) (Goyal 2017) or 0.1 mg/kg on days 1 to 5 every 28 days (Ref).
Hairy cell leukemia: Note: If active infection is present, manage appropriately prior to administering cladribine (Ref).
IV: 0.14 mg/kg/day over 2 hours for 5 days for 1 cycle (Ref) or 0.1 mg/kg/day continuous infusion for 7 days for 1 cycle (Ref) or 0.09 mg/kg/day continuous infusion for 7 days for 1 cycle (Ref) 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) (Ref) or 5.6 mg/m2 over 2 hours once daily for 5 days as a single course, followed 28 days later by rituximab (Ref).
SUBQ (off-label route): 0.1 to 0.14 mg/kg/day for 5 days for 1 cycle (Ref).
Langerhans cell histiocytosis (multifocal or multisystem ) (off-label use): Note: Maximum response is generally obtained by cycle 4; limiting cladribine to 4 cycles may reduce the rate of severe cytopenias (Ref).
IV: 0.14 mg/kg on days 1 to 5 every 28 days or 5 mg/m2 on days 1 to 5 every 28 days; the median number of cycles administered was 4 (range: 1 to 9) (Ref) or 0.14 mg/kg on days 1 to 5 every 28 days for 3 to 6 cycles depending on response (Ref).
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 (Ref). Initiating oral cladribine during concomitant treatment with immunosuppressive or myelosuppressive therapies is not recommended.
Oral: 3.5 mg/kg cumulative dose over 2 years, administered in 2 treatment courses as 1.75 mg/kg in each year. The 1.75 mg/kg dose is further divided over 2 cycles, each cycle lasting 4 to 5 consecutive days; do not administer more than 20 mg/day.
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.
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 (Ref).
Waldenström macroglobulinemia (off-label use):
IV: 0.1 mg/kg/day continuous infusion for 7 days every 4 weeks for 2 cycles (Ref) or 0.12 mg/kg/day for 5 consecutive days every 28 days for 3 to 8 cycles depending on response (Ref).
SUBQ: 0.1 mg/kg/day for 5 consecutive days every month for 4 cycles (in combination with rituximab) (Ref).
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:
eGFR-based dosing:
eGFR ≤50 mL/minute: Use is not recommended (Ref).
Creatinine clearance-based dosing:
CrCl 10 to 50 mL/minute: Administer 75% of dose (Ref).
CrCl <10 mL/minute: Administer 50% of dose (Ref).
Hemodialysis: Use is not recommended (Ref).
Continuous renal replacement therapy (CRRT): Administer 50% of dose (Ref).
Oral:
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl <60 mL/minute: Use is not recommended.
Hepatic impairment prior to treatment initiation:
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-Turcotte-Pugh class A): Dosage adjustment is not likely necessary (Ref).
Moderate or severe impairment (Child-Turcotte-Pugh class B or C): Use is not recommended (Ref).
Oral:
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.
Moderate to severe impairment (Child-Turcotte-Pugh classes B and C): Use is not recommended (has not been studied).
Hepatotoxicity (eg, unexplained liver enzyme elevations or symptoms suggestive of hepatic dysfunction [eg, abdominal pain, anorexia, fatigue, jaundice, unexplained nausea, dark urine, and/or vomiting]) during treatment: Oral: Measure serum transaminases and total bilirubin immediately and interrupt or discontinue cladribine therapy.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
IV:
>10%:
Hematologic & oncologic: Anemia (severe: 37%), bone marrow depression (34%; may be delayed onset), febrile neutropenia (47%), neutropenia (severe: 70%), thrombocytopenia (12%)
Infection: Bacterial infection (12%), infection (28%; serious infection: 6% [including pneumonia, septicemia])
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: Cellulitis, ecchymosis, hyperhidrosis, macular eruption, pruritus, skin rash
Gastrointestinal: Abdominal pain, constipation, decreased appetite, diarrhea, flatulence, nausea, vomiting
Hematologic & oncologic: Bruise, decreased CD-4 cell count, petechia, purpuric disease
Infection: Bacteremia
Local: Injection-site reaction (including bleeding at injection site, cellulitis at injection site, erythema at injection site, pain at injection site), localized edema, localized infection
Nervous system: Anxiety, asthenia, chills, dizziness, fatigue, headache, insomnia, malaise, myasthenia, pain
Neuromuscular & skeletal: Arthralgia, myalgia
Respiratory: Abnormal breath sounds, cough, dyspnea, rales
Oral:
>10%:
Hematologic & oncologic: Decreased hemoglobin (26%), decreased neutrophils (27%; severe: 4%), decreased platelet count (11%), lymphocytopenia (24% to 87%)
Hypersensitivity: Hypersensitivity reaction (11%; severe hypersensitivity reaction: <1%)
Infection: Infection (49%; including bacterial infection, fungal infection, parasitic infection, serious infection, viral infection)
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%)
Infection: Herpes virus infection (6%), herpes zoster infection (2%; serious: <1%)
Nervous system: Depression (5%), insomnia (6%)
Neuromuscular & skeletal: Arthralgia (≤7%), arthritis (≤7%), back pain (8%)
Respiratory: Bronchitis (5%)
Miscellaneous: Fever (5%)
<1%:
Cardiovascular: Heart failure, myocarditis
Hepatic: Hepatic injury
Nervous system: Status epilepticus, tonic-clonic seizure
Respiratory: Tuberculosis
Frequency not defined:
Hematologic & oncologic: Malignant neoplasm (including malignant melanoma, ovarian carcinoma, pancreatic adenocarcinoma)
Infection: Coccidioidomycosis
Renal: Pyelonephritis
Postmarketing (any formulation):
Dermatologic: Viral skin infection
Hematologic & oncologic: Tumor lysis syndrome
Infection: Cryptococcosis, histoplasmosis, nocardiosis, toxoplasmosis, varicella zoster infection
Nervous system: Neurotoxicity (severe), progressive multifocal leukoencephalopathy
Respiratory: Respiratory tract infection
Hypersensitivity to cladribine or any component of the formulation.
Oral tablet: Current malignancy; pregnancy; individuals 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 and for 10 days after last dose).
Oral tablet [Canadian product]: Additional contraindications (not in the 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: Dose-dependent myelosuppression (neutropenia, anemia, and thrombocytopenia) is common with cladribine injection 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.
• 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 of cladribine. Significant and life-threatening liver injury has been reported in patients on oral therapy ~30 days after initiation; patients with preexisting liver disease and/or taking other hepatotoxic drugs may be at increased risk.
• Hypersensitivity: Hypersensitivity reactions have occurred.
• Infection: Serious and potentially fatal infections (bacterial, viral, parasitic, and fungal) have been reported. Cryptococcosis, histoplasmosis, nocardiosis, toxoplasmosis, and varicella zoster have been reported postmarketing. Due to neutropenia and T-cell depletion, risk versus benefit of treatment should be evaluated in patients with active infections. 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]). Initiating oral cladribine during concomitant treatment with immunosuppressive or myelosuppressive therapies is not recommended.
• Kidney toxicity: 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.
• Malignancy: 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 versus risks of cladribine oral tablets based on individual patient factors. Follow standard cancer screening guidelines in patients treated with cladribine oral tablets.
• Neurotoxicity: Serious, dose-related neurologic toxicity (including irreversible paraparesis and quadriparesis) has been reported with continuous IV 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. 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.
• Tumor lysis syndrome: With high tumor burden, tumor lysis syndrome and subsequent hyperuricemia may occur (rare).
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:
• 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 varicella zoster virus (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 .
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
Solution (Cladribine Intravenous)
10 mg/10 mL (per mL): $42.00 - $52.20
Tablet Therapy Pack (Mavenclad (10 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (4 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (5 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (6 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (7 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (8 Tabs) Oral)
10 mg (per each): $12,967.81
Tablet Therapy Pack (Mavenclad (9 Tabs) Oral)
10 mg (per each): $12,967.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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)
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.
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 (Ref).
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.
Hazardous agent (NIOSH 2024 [table 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 2023; NIOSH 2024; USP-NF 2020).
For injectable cladribine, follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.
Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light. A precipitate may develop at low temperatures and may be resolubilized at room temperature or by shaking the solution vigorously. Inadvertent freezing does not affect the solution; if freezing occurs prior to dilution, allow to thaw naturally prior to reconstitution; do not heat or microwave; do not refreeze.
Solutions for infusion diluted in NS in PVC containers are stable for 24 hours at room temperature and normal lighting conditions.
24-hour continuous infusion: Dilutions in NS for infusion should be used promptly; if not used promptly, the 24-hour infusion may be stored refrigerated for up to 8 hours prior to administration.
7-day continuous infusion: Dilutions in NS for infusion should be used promptly; if not used promptly, the 7-day infusion may be stored refrigerated for up to 8 hours prior to administration. Reconstituted solution is stable for 7 days (when diluted in bacteriostatic NS) in a CADD medication cassette reservoir. For patients weighing >85 kg, the effectiveness of the preservative in the bacteriostatic diluent may be reduced (due to dilution).
Oral tablet: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture. Store in original packing until immediately before use.
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/2024/022561s009lbl.pdf#page=29
Parenteral: Treatment of active hairy cell leukemia (FDA approved in adults); has also been used for acute myeloid leukemia and refractory Langerhans cell histiocytosis.
Oral: Treatment of relapsing forms of multiple sclerosis, including relapsing-remitting and active secondary progressive disease in patients who have had inadequate response or are intolerant to other therapies for multiple sclerosis (FDA approved in adults).
Cladribine may be confused with clevidipine, clofarabine, cytarabine, fludarabine.
Leustatin may be confused with leucovorin, lovastatin.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; contraindicated in pregnancy [oral tablet]; immunosuppressant agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, P-glycoprotein (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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Agents that Undergo Intracellular Phosphorylation: May decrease therapeutic effects of Cladribine. Risk X: Avoid
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
BCRP/ABCG2 Inducers: May decrease serum concentration of Cladribine. Risk C: Monitor
BCRP/ABCG2 Inhibitors: May increase 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
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. 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 increase immunosuppressive effects of Cladribine. Risk X: Avoid
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects 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 increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Elacestrant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Immunosuppressants (Cytotoxic Chemotherapy): May increase immunosuppressive effects of Cladribine. Risk X: Avoid
Immunosuppressants (Miscellaneous Oncologic Agents): May increase immunosuppressive effects of Cladribine. Risk X: Avoid
Immunosuppressants (Therapeutic Immunosuppressant Agents): May increase immunosuppressive effects of Cladribine. Risk X: Avoid
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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) Transporters: May increase 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 increase adverse/toxic effects of Interferons (Beta). Specifically, the risk for lymphopenia may be increased. Risk X: Avoid
Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Lenograstim: Antineoplastic Agents may decrease therapeutic effects 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
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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 increase immunosuppressive effects of Cladribine. Risk X: Avoid
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Myelosuppressive Agents: Cladribine may increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Cladribine. Risk C: Monitor
Palifermin: May increase adverse/toxic effects 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
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of 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
Pretomanid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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
Sparsentan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects 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
Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Cladribine may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Cladribine may decrease therapeutic effects of Vaccines (Live). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Cladribine may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting 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
Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Vimseltinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid concomitant use of vimseltinib and BCRP substrates when possible. If combined, monitor for increased effects and toxicities of the BCRP substrate and consider dose adjustments. Risk D: Consider Therapy Modification
Voxilaprevir: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Recombinant): Cladribine may decrease therapeutic effects 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
Evaluate pregnancy status prior to use; exclude pregnancy prior to each treatment course in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of cladribine, regardless of the route of administration/indication for treatment. Patients with partners who could become pregnant should also use effective contraception during therapy and for 6 months after the last cladribine dose. Use of oral cladribine is contraindicated in patients of reproductive potential who do not plan to use effective contraception during therapy and for 6 months after the last dose.
In general, disease-modifying therapies for multiple sclerosis are stopped prior to a planned pregnancy except in patients at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]). Consider use of agents other than cladribine for patients at high risk of disease reactivation who are planning a pregnancy. Delaying pregnancy is recommended for patients 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. Discontinue cladribine if pregnancy occurs during treatment; use of oral cladribine during pregnancy is contraindicated.
Outcome data related to the use of cladribine for the treatment of hairy cell leukemia (Daver 2013) or multiple sclerosis (Dost-Kovalsky 2023; Giovannoni 2020) during pregnancy are limited.
In general, disease-modifying therapies for multiple sclerosis are not initiated during pregnancy, except in patients at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]).
Data collection to monitor pregnancy and infant outcomes following exposure to cladribine for the treatment of patients with multiple sclerosis is ongoing. Health care providers are encouraged to enroll patients exposed to cladribine during pregnancy or within 6 months prior to pregnancy in the EMD Serono’s Adverse Event reporting line (1-800-283-8088 ext. 5563) or by faxing (1-781-681-2961); patients may also enroll themselves.
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
CBC with differential (particularly during the first 4 to 8 weeks post-treatment); baseline and periodic renal and hepatic function tests; body temperature (fever); bone marrow biopsy (after CBC has normalized; to confirm treatment response); signs and symptoms of neurotoxicity
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: IV: ~9 L/kg; penetrates CSF (CSF concentrations are ~25% of plasma concentrations); Oral: 480 to 490 L.
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 (IV: 18%; Oral: 28.5%).
Altered kidney function:
Mild impairment (CrCl 60 to 90 mL/minute): Oral: 18% decrease in total clearance; 25% increase in cladribine exposure
Moderate or serious impairment: Limited clinical experience.
