DrugindexOnline^{2nd edition}

Pronouncation: (KLAD-rih-BEAN)
Class: Purine analog

Trade Names:
Leustatin
- Solution for injection 1 mg/mL

Mechanism of Action

Pharmacology

The selective toxicity of cladribine toward certain normal and malignant lymphocyte and monocyte populations is based on the relative activities of deoxycytidine kinase, deoxynucleotidase, and adenosine deaminase. In cells with a high ratio of deoxycytidine kinase to deoxynucleotidase, cladribine passively crosses the cell membrane. Cladribine is cytotoxic to actively dividing and quiescent lymphocytes and monocytes, inhibiting DNA synthesis and repair.

Pharmacokinetics

Distribution

Vd is about 4.5 L/kg. About 20% protein bound.

Elimination

The t _½ is about 5.4 h. Cl is about 978 mL/h/kg.

Indications and Usage

Adult

Hairy cell leukemia.

Unlabeled Uses

Chronic lymphocytic leukemia, non-Hodgkin lymphoma, acute myeloid leukemia.

Contraindications

Standard considerations.

Dosage and Administration

Hairy Cell Leukemia
Adults

Continuous IV infusion 0.09 mg/kg/day for 7 days, single course. It can be prepared each day as a 24-h infusion or as a single dose to infuse over 7 days in an ambulatory infusion pump. For patients weighing more than 85 kg, preparation of a single dose for administration over 7 days is not advised because solutions may be inadequately preserved because of increased dilution of benzyl alcohol.

General Advice

• Avoid mixing with dextrose 5% because increased degradation may occur.

• Daily infusion
• Mix calculated dose of cladribine in 500 mL of sodium chloride 0.9% solution prior to infusion.
• Solutions diluted in sodium chloride 0.9% are stable for at least 24 h at room temperature in PVC containers.

• 7-day infusion
• Diluted solutions prepared in bacteriostatic sodium chloride 0.9% (with benzyl alcohol) are stable for at least 7 days at room temperature.

Storage/Stability

Store vials in refrigerator and protect from light. May be frozen. If frozen, allow to thaw at room temperature. Do not heat, microwave, or refreeze. After dilution, cladribine solution may be stored in the refrigerator for up to 8 h prior to administration.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Fatigue; headache; dizziness; insomnia.

Dermatologic

Rash; injection-site reactions.

GI

Nausea; vomiting.

Hematologic

Bone marrow suppression; decreased CD4 count.

Musculoskeletal

Myalgia; arthralgia.

Miscellaneous

Fever.

Precautions

Warnings Bone marrow suppression Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, has been observed in patients treated with cladribine, especially at high doses. Nephrotoxicity Associated with high dose and concurrent nephrotoxic drugs. Neurotoxicity Severe cases more common with continuous high-dose infusions. Serious neurological toxicity (including irreversible paraparesis and quadraparesis) has been reported with doses 4 to 9 times the recommended dose for hairy cell leukemia. Severe neurological toxicity has been rarely reported with standard dosing regimens.

Monitor CBC Monitor CBC at baseline and for 4 to 8 wk after therapy. Hyperuricemia May occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol. Neurologic exam Perform baseline neurologic exam and monitor for 4 to 12 wk after therapy. Renal function Assess renal function at baseline and throughout therapy.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Extravasation risk

Local irritation or phlebitis may occur. Refer to the institution's specific protocol.

Fever

Fever 37.8°C (100°F or higher) was associated with the use of cladribine in about 66% of patients in the first month of therapy.

Overdosage

Symptoms

Irreversible neurologic toxicity (paraparesis/quadriparesis); acute nephrotoxicity; severe bone marrow suppression resulting in neutropenia, anemia, and thrombocytopenia.

Patient Information

• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver to carefully follow instructions for supplemental therapies designed to protect the kidneys from excessive uric acid (eg, increased fluid intake, allopurinol, urinary alkalinizing agents).
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills, or other signs of infection; sore throat; unusual bleeding or bruising.
• Advise patient, family, or caregiver to report any of the following to the health care provider: persistent nausea, vomiting or appetite loss; persistent fatigue; injection-site reaction.