Cladribine

The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes.

• Cladribine tablets are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease in adults. Because of its safety profile, use of cladribine tablets is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS [ see Warnings and Precautions (5) ].ICD-10: G35

• Cladribine tablets are contraindicated: in patients with current malignancy [ see Warnings and Precautions (5.1) ] . in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course for females, and 14 weeks for males.contraindicated

Assessments are required prior to starting each cladribine treatment course. (2.1) Cumulative dosage of 3.5 mg/kg administered orally and divided into 2 treatment courses (1.75 mg/kg per treatment course). Each treatment course is divided into 2 treatment cycles. (2.2) Cladribine tablets are a cytotoxic drug. (2.4) Separate administration from any other oral drug by at least 3 hours. (2.4) 2.1 Assessments Prior to Starting Each Cladribine Treatment Course Cancer Screening Follow standard cancer screening guidelines because of the risk of malignancies [ see Boxed Warning and Warnings and Precautions (5.1) ]. Pregnancy Exclude pregnancy prior to treatment with cladribine tablets in females of reproductive potential [ see Contraindications (4) , Warnings and Precautions (5.2) , and Use in Specific Populations (8.1, 8.3) ]. Complete Blood Count (CBC) Obtain a CBC with differential including lymphocyte count [ see Dosage and Administration (2.5) and Warnings and Precautions (5.3) ]. Lymphocytes must be: within normal limits before initiating the first treatment course at least 800 cells per microliter before initiating the second treatment course If necessary, delay the second treatment course for up to 6 months to allow for recovery of lymphocytes to at least 800 cells per microliter. If this recovery takes more than 6 months, the patient should not receive further treatment with cladribine tablets. Infections [ see Warnings and Precautions (5.4) ] Exclude HIV infection. Perform tuberculosis screening. Screen for hepatitis B and C. Evaluate for acute infection.

Lymphopenia: Monitor lymphocyte counts before, during and after treatment. (5.3) Infections: Serious, including life-threatening and fatal infections, have occurred. Screen patients for active and latent infections; delay treatment until infection is fully resolved or controlled. Vaccination of patients seronegative to varicella zoster virus (VZV) is recommended prior to treatment. Vaccination of patients seropositive to VZV with zoster vaccine recombinant, adjuvanted, is recommended prior to or during treatment. Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter. Monitor for infections. (5.4) Hematologic toxicity: Monitor complete blood count before, during and after treatment. (5.5) Graft-versus-host-disease with blood transfusion: Irradiation of cellular blood components is recommended. (5.6) Liver injury: Clinically significant liver injury has occurred. Obtain tests prior to treatment. Discontinue if clinically significant injury is suspected. (5.7) 5.1 Malignancies Treatment with cladribine tablets may increase the risk of malignancy. In controlled and extension clinical studies worldwide, malignancies occurred more frequently in cladribine-treated patients [10 events in 3,754 patient-years (0.27 events per 100 patient-years)], compared to placebo patients [3 events in 2,275 patient-years (0.13 events per 100 patient-years)].

The following serious adverse reactions and potential risks are discussed, or discussed in greater detail, in other sections of the labeling: Malignancies [ see Warnings and Precautions (5.1) ] Risk of Teratogenicity [ see Warnings and Precautions (5.2) ] Lymphopenia [ see Warnings and Precautions (5.3)] Infections [ see Warnings and Precautions (5.4) ] Hematologic Toxicity [ see Warnings and Precautions (5.5) ] Graft-Versus-Host Disease With Blood Transfusion [ see Warnings and Precautions (5.6) ] Liver Injury [ see Warnings and Precautions (5.7) ] Hypersensitivity [ see Warnings and Precautions (5.8) ] Cardiac Failure [ see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence > 20%) are upper respiratory tract infection, headache, and lymphopenia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In the clinical trial program of cladribine in MS, 1,976 patients received cladribine for a total of 9,509 patient years. The mean time on study including follow-up was approximately 4.8 years, and approximately 24% of cladribine-treated patients had approximately 8 years of time on study including follow-up.

8.1 Pregnancy Risk Summary Cladribine tablets are contraindicated in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception. There are no adequate data on the developmental risk associated with use of cladribine in pregnant women. Cladribine was embryolethal when administered to pregnant mice and produced malformations in mice and rabbits [ see Data ]. The observed developmental effects are consistent with the effects of cladribine on DNA [ see Contraindications (4) and Warnings and Precautions (5.2) ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When cladribine was administered intravenously (0, 0.5, 1.5, or 3 mg/kg/day) to pregnant mice during the period of organogenesis, fetal growth retardation and malformations (including exencephaly and cleft palate) and embryofetal death were observed at the highest dose tested. An increase in skeletal variations was observed at all but the lowest dose tested. There was no evidence of maternal toxicity.

Metabolism

Cladribine is a prodrug that becomes active upon phosphorylation to its 2-chlorodeoxyadenosine triphosphate (Cd-ATP) metabolite. The pharmacokinetic parameters presented below were assessed following oral administration of cladribine 10 mg, unless otherwise specified.

There is no experience with overdose of cladribine tablets. Lymphopenia is known to be dose- dependent. Particularly close monitoring of hematological parameters is recommended in patients who have been exposed to an overdose of cladribine tablets [ see Warnings and Precautions (5.3, 5.5) ]. There is no known specific antidote to an overdose of cladribine tablets. Treatment consists of careful observation and initiation of appropriate supportive measures. Discontinuation of cladribine tablets may need to be considered. Because of the rapid and extensive intracellular and tissue distribution, hemodialysis is unlikely to eliminate cladribine to a significant extent.

• Feb 28, 2000ANDAANDA075405Hikma
• Apr 22, 2004ANDAANDA076571Fresenius Kabi Usa
• Mar 29, 2019NDANDA022561Emd Serono Inc
• Nov 25, 2019ANDAANDA210856Hisun Pharm Hangzhou
• Nov 24, 2025ANDAANDA218425Apotex
• Mar 27, 2026ANDAANDA215547Hopewell Pharma

1. 1Fatigue7898.5%
2. 2Headache6547.1%
3. 3Lymphocyte Count Decreased4715.1%
4. 4Multiple Sclerosis Relapse4685.1%
5. 5Nausea4104.4%
6. 6Pneumonia3914.2%
7. 7White Blood Cell Count Decreased3483.8%
8. 8Off Label Use3273.5%
9. 9Pyrexia2863.1%
10. 10Drug Ineffective2833.1%
11. 11Urinary Tract Infection2712.9%
12. 12Multiple Sclerosis2492.7%
13. 13Asthenia2342.5%
14. 14Lymphopenia2222.4%
15. 15Febrile Neutropenia2092.3%

Recent PubMed references pinned to Cladribine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Cladribine treatment in pediatric-onset multiple sclerosis: real-world clinical outcomes and safety insights.
  Frontiers in immunology · 2026 · Ganelin-Cohen E, Wexler Y, Kraus S, et al.
  PMID 42148068DOI 10.3389/fimmu.2026.1727925
• Dynamics of Spinal Fluid Immune Cell Alterations Following Cladribine Tablet Treatment in Multiple Sclerosis.
  Neurology(R) neuroimmunology & neuroinflammation · 2026 · Smirnov RA, Cantoni C, Lee K, et al.
  PMID 41990287DOI 10.1212/NXI.0000000000200565
• The comparative efficacy of cladribine tablets versus alternative disease-modifying treatments for relapsing-remitting multiple sclerosis: Updated meta-regression estimates by patient subgroup.
  Multiple sclerosis and related disorders · 2026 · Harty GT, Jones M, J S, et al.
  PMID 41926863DOI 10.1016/j.msard.2026.107160
• Comparative assessment of treatment switching in patients with multiple sclerosis receiving cladribine tablets versus fingolimod, dimethyl fumarate, and teriflunomide.
  Multiple sclerosis and related disorders · 2026 · Lobo C, Rey GG, Zhao X, et al.
  PMID 41894909DOI 10.1016/j.msard.2026.107143
• Long-term outcomes of cladribine tablets in multiple sclerosis: Treatment completion, persistence, and subsequent therapy transitions in Southeast Europe.
  Multiple sclerosis and related disorders · 2026 · Krbot Skorić M, Brecl Jakob G, Rajda C, et al.
  PMID 41886879DOI 10.1016/j.msard.2026.107151
• The Regimen of Cladribine, Cytarabine, and Venetoclax (CAV) Induces Apoptosis in Acute Myeloid Leukemia Cells by Enhancing DNA Damage.
  Journal of visualized experiments : JoVE · 2026 · Liu FT, Huang YH, Ge SS, et al.
  PMID 41871015DOI 10.3791/69797
• The effect of cladribine-containing conditioning regimen on the efficacy and safety of allogeneic hematopoietic stem cell transplantation for children with acute lymphoblastic leukemia.
  Stem cell research & therapy · 2026 · Li X, Hu K, Lin S, et al.
  PMID 41851884DOI 10.1186/s13287-026-04973-y
• Treatment-free remission in MS: long-term disease control with cladribine tablets.
  Journal of neurology · 2026 · Wiendl H, Gold R, Pul R, et al.
  PMID 41844910DOI 10.1007/s00415-026-13753-w

The 10 most recently updated of 174 ClinicalTrials.gov registrations naming Cladribine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
  Recruiting · Phase 1 · Phase 2 · Interventional · 80 enrolled · M.D. Anderson Cancer Center
  NCT04047641updated 2026-06-12
• Cladribine and Rituximab in Treating Patients With Hairy Cell Leukemia
  Recruiting · Phase 2 · Interventional · 150 enrolled · M.D. Anderson Cancer Center
  NCT00412594updated 2026-06-11
• IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.
  Recruiting · Phase 3 · Interventional · 339 enrolled · Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
  NCT06713837updated 2026-06-10
• Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
  Recruiting · Phase 2 · Interventional · 145 enrolled · M.D. Anderson Cancer Center
  NCT03586609updated 2026-06-08
• Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia
  Completed · Phase 1 · Phase 2 · Interventional · 37 enrolled · M.D. Anderson Cancer Center
  NCT04848974updated 2026-06-05
• A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
  Recruiting · Phase 2 · Interventional · 60 enrolled · M.D. Anderson Cancer Center
  NCT05365035updated 2026-06-05
• Testing the Combination of Anti-cancer Drugs, Tovorafenib Plus Rituximab, in Patients With Hairy Cell Leukemia
  Recruiting · Phase 1 · Phase 2 · Interventional · 84 enrolled · National Cancer Institute (NCI)
  NCT06965114updated 2026-06-03
• A Study of Vemurafenib and Obinutuzumab Compared to Cladribine and Rituximab in People With Hairy Cell Leukemia (HCL)
  Recruiting · Phase 2 · Interventional · 86 enrolled · Memorial Sloan Kettering Cancer Center
  NCT06561360updated 2026-05-26
• Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis (MyClad)
  Recruiting · Phase 3 · Interventional · 264 enrolled · Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  NCT06463587updated 2026-05-22
• Cladribine Tablets Level of Response Predictors in Clinical Practice (CLODINA)
  Active not recruiting · Observational · 367 enrolled · Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  NCT05797740updated 2026-05-22

Frequently asked questions

How does Cladribine work?

The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes.

What is Cladribine used for?

According to FDA labeling, Cladribine carries indications including: Cladribine tablets are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease in adults. Because of its safety profile, use of cladribine tablets is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS [ see Warnings and Precautions (5) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Cladribine?

Cladribine is classified as Purine analogues, Selective immunosuppressants, Purine Antimetabolite, Nucleic Acid Synthesis Inhibitors, Decreased DNA Integrity, Decreased DNA Replication.

What are the brand names for Cladribine?

Cladribine is marketed under brand names including Mavenclad.

What are the contraindications for Cladribine?

Cladribine labeling lists contraindications including: Cladribine tablets are contraindicated: in patients with current malignancy [ see Warnings and Precautions (5.1) ] . in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course for females, and 14 weeks for males.. Always consult the full prescribing information and a clinician.