Cladribine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antimetabolites

Antineoplastic agents

Included in the formulation

Vero-Cladribine

solution d / infusion

VEROPHARM SA Russia

АТХ:

L.01.B.B.04 Cladribine

Pharmacodynamics:

An analogue of 2'-deoxyadenosine, which is part of the DNA molecule. Thereby cladribine (2-chloro-2'-deoxyadenosine) has a cytotoxic effect on fissionable and non-dividing cells, inhibiting the synthesis and repair of DNA. Inhibition of ribonucleotide reductase, which catalyzes the synthesis of deoxynucleoside triphosphates involved in the synthesis of DNA polymerases. Besides cladribine inhibits DNA polymerase, which also leads to the cessation of DNA synthesis. Activation of specific endonuclease leads to single-strand breaks in the DNA chain. As a result, there is a death of tumor lymphoid cells that have a high level of deoxycytidine kinase activity and a low 5'-nucleotidase in comparison with cells of other tissues.

Pharmacokinetics:

After intravenous administration, up to 25% of the drug is in the cerebrospinal fluid. Since the activity of deoxycytidine kinase is higher than that of 5'-nucleotidase, and also because of the drug's resistance to adenosine deaminase, all three phosphorylated forms of 2-chloro-2'-deoxyadenosine rapidly accumulate in the cell.

Metabolism in the liver.

The half-life is 5.7-19.7 hours.Elimination by the kidneys.

Indications:

It is used for treatment hairy cell leukemia.

ICD-10

II.C81-C96.C91.4 Hairy cell leukemia (Leukemic reticuloendotheliosis)

Contraindications:

Leukopenia, thrombocytopenia, immunodeficiency, severe impairment of liver and kidney function, individual intolerance, childhood.

Carefully:

Renal failure, elderly age.

Pregnancy and lactation:

Recommendations for FDA - Category X. Contraindicated in pregnancy and lactation.

Dosing and Administration:

Intravenously drip for 2 or 24 hours. The recommended dose: 0.09-0.1 mg / kg per day for 7 days.

The highest daily dose: 0.1 mg / kg.

The highest single dose: 0.1 mg / kg.

Side effects:

Central and peripheral nervous system: fatigue, dizziness, aphasia, convulsions.

The system of hematopoiesis: anemia, thrombocytopenia, and leukopenia.

Respiratory system: cough, rapid breathing, interstitial pneumonitis.

Digestive system: ulcerative stomatitis, anorexia, nausea, rarely - melena, diarrhea, pancreatitis, fatty degeneration of the liver.

Musculoskeletal system: arthralgia, myalgia.

Urinary system: hematuria, cystitis.

Reproductive system: oligospermia, decreased libido, menstrual irregularities, impotence.

Allergic reactions.

Overdose:

Anemia, neutropenia, thrombocytopenia, acute nephrotoxicity, irreversible neurotoxicity: paresis / tetraparesis.

Treatment is symptomatic.

Interaction:

Antibiotics and allopurinol enhance skin rash.

Simultaneous use with other myelotoxic drugs leads to an additive inhibition of bone marrow function.

Mixing with a 5% solution of dextrose increases the degradation of cladribine.

Special instructions:

Treatment with cladribine is carried out under the supervision of a doctor who has experience of antitumor therapy. Monitoring of liver and kidney functions, blood tests. With the development of hyperthermia against the background of neutropenia, the appointment of antibacterial drugs is recommended.

Instructions

Cladribine (Cladribinum)