Cladribine

Cladribine is available in two distinct forms for two distinct conditions:

• Cladribine tablets (Mavenclad, oral): Treats relapsing forms of multiple sclerosis (MS) in adults, including relapsing-remitting MS and active secondary progressive MS. Generally used when other MS treatments haven't worked or aren't tolerated. Not recommended for clinically isolated syndrome (CIS).
• Cladribine injection (intravenous): Treats active hairy cell leukemia — a rare blood cancer — in adults with significant anemia, low neutrophils (infection-fighting white cells), low platelets, or symptoms from the disease.

Cladribine is a type of drug called a purine antimetabolite — it mimics a building block of DNA and gets taken up by lymphocytes (immune cells). Once inside, it is converted into an active form that accumulates to toxic levels, disrupting the cell's ability to make and repair DNA. This kills off large numbers of B and T lymphocytes — the immune cells responsible for MS-related inflammation, and the cancerous cells in hairy cell leukemia. Unlike many chemotherapy drugs, cladribine can kill both actively dividing cells and resting (non-dividing) cells.

Certain cells are more vulnerable because of a specific enzyme imbalance inside them — they build up the toxic form of cladribine faster than they can get rid of it. This gives cladribine a degree of selectivity toward lymphocytes and monocytes.

Dosing is very different depending on the form:

• Oral tablets (Mavenclad): Taken by mouth in two yearly treatment courses, each divided into two short cycles of daily dosing. Any other oral drug must be taken at least 3 hours apart. Can be taken with or without food, though a high-fat meal slightly delays absorption (not considered clinically significant). After completing both courses, no additional cladribine is given for at least the following 2 years.
• IV injection: Given by continuous intravenous infusion over 7 consecutive days in a clinical or hospital setting. It is prepared by healthcare professionals and is not a self-administered treatment.

Always follow your prescriber's exact schedule. Do not adjust doses on your own.

Side effects vary by formulation and are common — here are the most frequently reported:

• Fever and chills (very common with IV treatment, especially in the first month)
• Fatigue and weakness
• Nausea, vomiting, diarrhea
• Headache and dizziness
• Rash
• Low lymphocyte counts (lymphopenia) — experienced by the majority of MS patients on the tablets
• Decreased appetite
• Infections, including herpes/shingles

Serious reactions requiring prompt attention include signs of severe infection (high fever, difficulty breathing, painful rash), new neurological changes (weakness, vision loss, confusion — possible PML), signs of liver injury (jaundice, dark urine), or unusual bleeding. Contact your care team immediately if any of these occur.

• Cancer risk: Cladribine tablets may raise the risk of malignancy. It is contraindicated in current cancer and requires a careful risk discussion in those with prior cancer history. Standard cancer screening should continue throughout treatment.
• Severe fetal harm: Cladribine causes birth defects and embryo death in animals. Pregnancy must be excluded before each course; effective contraception is required during and for months after treatment for both women and men.
• Lymphopenia (low immune cell counts): Most patients will experience a significant drop in lymphocyte counts, increasing infection risk. Counts are monitored closely and the second treatment course may be delayed if counts are too low.
• Serious infections: Life-threatening bacterial, viral, fungal, and parasitic infections have occurred, including tuberculosis reactivation, hepatitis B reactivation, herpes zoster (shingles), and rare brain infection (PML). Screening for HIV, TB, and hepatitis is required before starting.
• Blood count suppression: Low neutrophils, hemoglobin, and platelets have all been reported, sometimes severely. Regular blood count monitoring is required.
• Liver injury: Clinically significant liver damage has been reported. Liver tests should be checked before starting treatment.
• Blood transfusions: If a transfusion is needed, irradiated blood products are recommended to reduce the risk of a rare but dangerous reaction called transfusion-associated graft-versus-host disease.

Cladribine can interact with several types of drugs — tell your care team about everything you take:

• Immunosuppressive or myelosuppressive drugs (e.g., other MS therapies, chemotherapy): Additive immune suppression — co-use is not recommended.
• Interferon-beta: May worsen lymphopenia — co-use not recommended.
• Antivirals/antiretrovirals (e.g., lamivudine, ribavirin, zidovudine, stavudine, zalcitabine): May block cladribine from being activated inside cells — avoid combining.
• Potent transporter inhibitors (e.g., ritonavir, cyclosporine, eltrombopag, dipyridamole): May change how much cladribine reaches its targets — avoid during dosing cycles.
• Potent inducers (e.g., rifampicin, St. John's Wort): May reduce cladribine's effectiveness.
• Live vaccines: Must not be given during treatment or while white blood cell counts are still low — risk of active vaccine infection. Live vaccines should be given at least 4–6 weeks before starting cladribine.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Current cancer: Cladribine tablets are contraindicated — cannot be used.
• Prior cancer or elevated cancer risk: Requires individual benefit-risk evaluation with your doctor.
• Active HIV infection: Contraindicated — must be excluded before starting.
• Active chronic infections (hepatitis B, hepatitis C, tuberculosis): Contraindicated — these must be screened for and treated first.
• Pregnancy: Contraindicated — can cause serious fetal harm. A negative pregnancy test is required before each course.
• Breastfeeding: Oral cladribine is contraindicated on dosing days and for 10 days after the last dose.
• Women of reproductive potential: Must use effective contraception during treatment and for at least 6 months after the last dose of each course.
• Men of reproductive potential: Must use contraception for at least 14 weeks after the last dose of each course.
• Moderate to severe kidney disease (creatinine clearance below 60 mL/min): Oral cladribine is not recommended.
• Moderate to severe liver disease (Child-Pugh score above 6): Oral cladribine is not recommended.
• Children under 18: Safety and effectiveness not established; not recommended due to cancer risk.
• Older adults: Use with caution — greater chance of reduced kidney, liver, or heart function with age.
• History of hypersensitivity to cladribine: Contraindicated.

Taking too much cladribine — particularly at high doses — has been associated with serious and potentially irreversible effects, including severe nerve damage causing progressive weakness or paralysis, acute kidney failure, and dangerous suppression of bone marrow (leading to very low blood counts).

There is no specific antidote. If overdose is suspected, the drug should be stopped and supportive medical care given. It is not known whether dialysis can remove cladribine from the body.

Cladribine tablets cause a predictable, dose-dependent drop in lymphocyte counts (white blood cells that drive immune activity). The lowest counts typically occur about 2 to 3 months after each treatment cycle starts, and counts fall further with the second course. By the end of the second year of treatment, most patients' counts begin recovering — the median time to recover from very low counts (below 500 cells per microliter) to a safer level (at least 800 cells per microliter) is about 28 weeks. For the IV formulation used in hairy cell leukemia, cladribine also causes prolonged suppression of CD4 immune cells, with counts remaining low for many months after treatment.

When taken by mouth, cladribine is about 40% absorbed, reaching peak blood levels in about 30 minutes on an empty stomach (slightly delayed with a high-fat meal, but the total amount absorbed is the same). It is a prodrug — meaning it only becomes active after being converted inside lymphocytes into its active form, cladribine triphosphate (Cd-ATP), which has an intracellular half-life of about 10 hours. The drug distributes widely in the body and can cross into the brain and spinal fluid. It is cleared roughly equally by the kidneys and other routes, with an estimated blood half-life of about 1 day. When given intravenously (for leukemia), it also distributes extensively — about 9 liters per kilogram — penetrates cerebrospinal fluid, and is only about 20% bound to plasma proteins, with a terminal half-life of roughly 5 to 7 hours depending on the study.

Store refrigerated 2° to 8°C (36° to 46°F). Protect from light during storage.