Cladribine is a cytostatic antitumor chemotherapeutic drug from the group of purine antagonists, an analogue of 2'-deoxyadenosine, which is part of the DNA molecule. Cladribine exhibits cytotoxic effects (due to the active metabolite of 5'-triphosphate-2-chloro-2'-deoxyadenosine) in relation to dividing and non-dividing cells, inhibiting DNA synthesis and repair (inhibits ribonucleotide reductase, which catalyzes the formation of deoxynucleoside triphosphates, activates DNA polymerase and activates endonuclease, which leads to single-stranded DNA breaks), which ultimately leads to cell death. Lymphoid cells are more sensitive to the drug (since they have a higher deoxycytidine kinase activity and low 5'-nucleotidase activity) than non-lymphoid cells.
Content
Pharmacokinetics
25% of the drug penetrates the CSF. Undergoes intracellular metabolism. At the initial stage, phosphorylation to 5'-monophosphate is carried out by deoxycytidine kinase. Since the activity of deoxycytidine kinase is higher than that for 5'-nucleotidase, as well as due to the drug's resistance to adenosine deaminase, all three phosphorylated forms of 2-chloro-2'-deoxyadenosine rapidly accumulate in the cell. With the on / in the introduction of T1 / 2 - 5.7-19.7 hours. It is excreted mainly by the kidneys (35%), a small amount (1%) of the intestines.
Indications
Hairy cell leukemia.
Contraindications
Hypersensitivity, moderate or severe CRF (CC less than 50 ml / min), moderate or severe hepatic insufficiency (4 or more on the Child-Pyug scale), the simultaneous use of myelosuppressive drugs, children (up to 16 years), pregnancy, lactation.
Caution
Inhibition of bone marrow function, infection.
Dosage
In / in a drop, in the form of 2- or 24-hour infusions. The dose and duration of treatment are determined depending on the characteristics of the course of the disease and the severity of the condition. The recommended dose is 0.09-0.1 mg / kg / day for 7 days. There is no evidence of an increase in the antitumor effect during additional courses.
Before administration, the required amount of concentrate is diluted in 0.5-1 l of a 0.9% NaCl solution; for 24 infusions, a bacteriostatic 0.9% NaCl solution is used (contains benzyl alcohol as a preservative).
Side effect
From the hemopoietic organs
Leukopenia, neutropenia, thrombocytopenia, anemia, pancytopenia, aplastic and hemolytic anemia; very rarely - myelodysplastic syndrome.
From the digestive system
Nausea, vomiting, anorexia, diarrhea, constipation, gastralgia, increased bilirubin and / or transaminases.
From the nervous system
Headache, dizziness, insomnia, peripheral sensory neuropathies.
From the cardiovascular system
Tachycardia, swelling.
From the respiratory system
Cough, rapid breathing, interstitial pneumonitis, changes in percussion sound and auscultatory characteristics of breathing.
On the part of the skin
Rash, peeling, skin itching, urticaria.
Local reactions
Erythema, pain, swelling, thrombosis, phlebitis.
Others
Hyperthermia, weakness, asthenia, fatigue, pain of various localization, purpura, petechiae, nosebleeds, decreased immunity; predisposition to opportunistic infections, infections caused by Herpes simplex, Herpes zoster, cytomegalovirus.
Overdose
Symptoms
Irreversible neurotoxicity (paresis / tetraparesis), acute nephrotoxicity, marked inhibition of bone marrow hematopoiesis (neutropenia, anemia, thrombocytopenia).
Treatment
Symptomatic, antidote unknown.
Interaction
When administered simultaneously or immediately after other myelotoxic drugs, additive inhibition of bone marrow function is possible.
When prescribed in high doses in combination with cyclophosphamide and radiation therapy, neurotoxicity (irreversible para- and tetraparesis) and nephrotoxicity (acute renal failure) increase.
Allopurinol and antibiotics enhance skin rashes.
When mixed with 5% dextrose solution - increased degradation of cladribine.
Special instructions
Treatment with the drug should be carried out under the supervision of a doctor with experience in the use of antitumor therapy. Myelosuppression caused by the drug is dose-dependent and usually reversible, manifests itself within a month from the moment of treatment. During treatment and for at least 4-8 weeks. After that, careful monitoring of hematological blood parameters is necessary.
Particular care should be taken in patients with initial inhibition of bone marrow function of any origin due to the risk of prolonged hypoplasia.
In some cases, treatment can lead to severe forms of immunosuppression with a decrease in the number of CD4 Β± white blood cells. If hyperthermia occurs during neutropenia, it is necessary to monitor the general condition of the patient during the first month of treatment and, if necessary, prescribe antibacterial therapy.
In case of development of neurotoxicity, drug treatment should be suspended until neurological symptoms resolve.
Treatment of patients with renal and / or liver failure should be carried out under the direct control of renal and hepatic function. Treatment should be discontinued if nephro- or hepatotoxicity develops.
Careful monitoring of elderly patients is necessary (due to the lack of pharmacokinetics data).