Drug information of cladribine

Mechanism of effect

Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate. which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death.

Pharmacodynamic

Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects

Pharmacokinetics

Oral bioavailability is 34 to 48%.Cladribine injection is bound approximately 20% to plasma proteins. Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate. An average of 18% of the administered dose has been reported to be excreted in urine of patients with solid tumors during a five-day continuous intravenous infusion of 3.5 to 8.1 mg/m2/day of Cladribine injection.

Drug indications

active Hairy Cell Leukemia

Dosage

Usual Adult Dose for Hairy Cell Leukemia 0.09 mg/kg/day by continuous IV infusion for 7 days.

Drug contraindications

hypersensitivity to drug or its components.

Side effects

nausea , Headache , insomnia , constipation , Tachycardia , abdominal pain , dizziness , vomiting , fatigue , rash , Diarrhea , Dyspnea , pruritus , neutropenia , anemia , Peripheral edema , Cough , fever , myalgia , anxiety , malaise , Arthralgia , flatulence , petechiae

Interactions

Medroxyprogesterone , Natalizumab , Vitamin A , Vitamin E , Carbamazepine , pimecrolimus , Trastuzumab , Clozapine , denosumab , prednisone , Adenovirus types 4 and 7 live, oral , trabectedine , dinutuximab , Duvelisib , Floxuridine , upadacitinib , Telbivudine , Edetate Calcium Disodium , Alemtuzumab , Dupilumab , Ocrelizumab , Ofatumumab , Risankizumab , vedolizumab , Brodalumab , Ustekinumab , Lopinavir and Ritonavir , Carmustine , Temsirolimus , Lorlatinib , Blinatumomab , Entecavir , Romidepsin , Dasatinib , lasmiditan , Meningococcal conjugate vaccine , Siltuximab , Daclizumab , Venetoclax , Selinexor , Brentuximab , Raltitrexed , Famtrastuzumab , Niraparib

Alerts

1-Cladribine injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy 2- Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. 3-Serious neurological toxicity (including irreversible paraparesis and quadraparesis) has been reported in patients who received Cladribine injection by continuous infusion at high doses (four to nine times the recommended dose for Hairy Cell Leukemia). Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard Cladribine dosing regimens. 4-Acute nephrotoxicity has been observed with high doses of Cladribine injection (four to nine times the recommended dose for Hairy Cell Leukemia), especially when given concomitantly with other nephrotoxic agents/therapies.

Points of recommendation

1-Periodic assessment of peripheral blood counts, particularly during the first four to eight weeks posttreatment, is recommended to detect the development of anemia, neutropenia and thrombocytopenia and for early detection of any potential sequelae (e.g., infection or bleeding). 2-monitoring of renal and hepatic function is also recommended, especially in patients with underlying kidney or liver dysfunction 3-69% of patients developed fevers, less than 1/3 of febrile events were associated with documented infection. Given the known myelosuppressive effects of Cladribine, practitioners should carefully evaluate the risks and benefits of administering this drug to patients with active infections 4-caution is advised when administering the drug to patients with known or suspected renal or hepatic insufficiency. 5-Cladribine injection must be diluted in designated intravenous solutions prior to administration

Pregnancy level

D

Related drugs

Mitomycin , Clofarabine , Pemetrexed , Pralatrexate