Cladribine – Uses, Dosage, Side Effects, Interaction

Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy? drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply.

Use in Cancer

Cladribine is approved to treat:

• Hairy cell leukemia.

Cladribine is also being studied in the treatment of other types of cancer.

Contraindications

• hepatic cirrhosis?,
• chronic kidney disease?,
• active malignancy,
• HIV, or tuberculosis?.
• Other contraindications to cladribine include a history of use of other immunosuppressants, including cyclophosphamide, azathioprine, methotrexate, or mitoxantrone.
• Sexually active men and women should receive counseling about cladribine’s teratogenicity and its effects on sperm quality and viability.
• a bad infection?
• decreased function of bone marrow?
• anemia
• a reduction in the body’s resistance to infection
• decreased function of bone marrow
• anemia
• a decreased number of lymphocytes in the blood
• inflammation? of the liver called hepatitis?
• severe? liver disease
• decreased kidney function
• abnormal liver function tests
• decreased blood platelets
• low levels of a type of white blood cell called neutrophils
• a painful condition that affects the nerves in the legs and arms called peripheral neuropathy
• severe liver disease
• the high amount of uric acid in the blood
• abnormal liver function tests
• pregnancy
• a patient who is producing milk and breastfeeding
• progressive multifocal leukoencephalopathy, a type of brain infection
• chronic kidney disease stage 3A (moderate)
• chronic kidney disease stage 3B (moderate)
• chronic kidney disease stage 4 (severe)
• chronic kidney disease stage 5 (failure)
• Child-Pugh class B liver impairment
• Child-Pugh class C liver impairment

Dosage

Strengths: 1 mg/mL; 10 mg

Hairy Cell Leukemia

• 0.09 mg/kg/day by continuous IV infusion for 7 days

Alternate dosing recommendation:

• Subcutaneous bolus injection: 0.14 mg/kg/day subcutaneously for 5 consecutive days
• IV infusion: 0.1 mg/kg/day IV for 7 consecutive days
• Under certain hematological conditions (e.g., recovery of severe myelosuppression) a small number of patients may require a second cycle and occasionally a third cycle to achieve a stable and prolonged response.

Cladribine for multiple sclerosis is an orally administered drug. The FDA-approved dose is 3.5 mg/kg given over two years, administered as 1.75 mg/kg per year. Two treatment courses are separated by twelve months. The first course is given over four to five consecutive days in the first month, followed by an equivalent dose over four to five consecutive days in the second month.

The second course of cladribine follows twelve months later with the same frequency and dosing. For an adult of average body weight, dosing is estimated at approximately 10 to 20 mg daily for 4 to 5 days. Prescribers need to follow the manufacturer’s specific guidelines for weight-based dosing according to approved federal guidelines of the Risk Evaluation and Mitigation Strategies (REMS) program. Monitoring occurs as described below to assure safe remission of the disease without severe lymphopenia or other adverse events.[rx]

Side Effects

The Most Common

• nausea
• vomiting
• diarrhea
• stomach pain
• constipation
• loss of appetite
• skin rash
• headache
• excessive sweating
• pain, redness, swelling, or sores in the place where the medication was injected
• pale skin
• excessive tiredness
• shortness of breath
• dizziness
• fast heartbeat

More Common

• constipation
• diarrhea
• dizziness
• headache
• joint pain
• loss of appetite
• muscle pain
• nausea
• the overall feeling of discomfort or illness
• sleeping problems
• unusual tiredness
• heart problems–swelling, rapid weight gain, feeling short of breath;
• low blood cell counts–fever, swollen glands, stomach pain, cough, runny nose, joint pain, mouth sores, skin sores or rash, easy bruising, unusual bleeding;
• liver problems–nausea, vomiting, stomach pain, tiredness, loss of appetite, yellowing of your skin or eyes, dark urine;
• signs of shingles–flu-like symptoms, tingly or painful blistering rash on one side of your body; or
• signs of tuberculosis: fever, cough, night sweats, loss of appetite, weight loss, and feeling very tired.
• low white blood cell counts; or
• cold symptoms such as stuffy nose, sneezing, and sore throat.

Rare

• numbness or tingling of the hands or feet
• pain, swelling, or redness at the site of injection
• shortness of breath
• signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, cuts that don’t stop bleeding)
• skin rash
• stomach pain
• sweating, pale skin
• swelling of feet or lower legs
• unusually fast heartbeat
• fever or chills
• flu-like symptoms (e.g., cough, hoarseness, sore throat, fever or chills)
• difficulty moving arms or legs
• shortness of breath
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools, spitting up of blood, vomiting blood or material that looks like coffee grounds)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of a severe skin reaction (such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort)
• signs of a skin reaction at the injection site (e.g., red streaks along vein where medication was injected, pain at injection site, redness, or warmth at site of injection)

Drug Interaction

Pregnancy and Lactation

AU TGA pregnancy category: D
US FDA pregnancy category: D

Pregnancy

This drug can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should use effective contraception during therapy and for 6 months after the last dose. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Men being treated with this drug should be advised not to father a child up to 6 months after the last dose.

Lactation

Data in one patient indicates that the drug is rapidly eliminated over 24 hours and undetectable at 48 hours after a dose. It is suggested that breastfeeding be withheld for at least 48 hours after a dose of cladribine and perhaps up to a week,[1,2] although the manufacturers recommend a 7-day (Europe) or 10-day (US) abstinence period. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breast milk.[3] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

References