Cladribine

Intravenous
Chronic lymphocytic leukaemia

Intravenous
Hairy cell leukaemia

Subcutaneous
Hairy cell leukaemia

Subcutaneous
Chronic lymphocytic leukaemia, Non-Hodgkin's lymphoma, Waldenstrom's macroglobulinaemia

Subcutaneous
Hairy cell leukaemia: Moderate to severe (CrCl ≤50 mL/min): Contraindicated.

Subcutaneous
Moderate to severe (Child-Pugh score >6): Contraindicated.

For IV infusion, the calculated dose to a polyvinyl Cl infusion bag containing 100-500 mL of 0.9% NaCl inj.

Incompatible w/ dextrose 5%.

For treatment of hairy cell leukaemia by SC inj: Moderate to severe renal and hepatic impairment; pregnancy and lactation.

Patient w/ pre-existing haematologic or immunologic abnormalities, active infection, high tumour burden or at risk for development of hyperuricaemia. Hepatic and renal impairment. Pregnancy and lactation.

Myelosuppression (e.g. neutropenia, anaemia, thrombocytopenia), prolonged CD4 lymphopenia and bone-marrow hypocellularity, haemolytic anaemia; fever, chills, diaphoresis, fatigue, malaise, nausea, abdominal pain, GI disturbance, rash, pruritus, urticaria, purpura, headache, anxiety, dizziness, abnormal breath/chest sounds, cough, dyspnoea, oedema, tachycardia, hypotension, arthralgia, myalgia; reversible increase in bilirubin and hepatic transaminases; conjunctivitis; lung infiltration, interstitial lung disease, pneumonitis, pulmonary fibrosis; confusion, neuropathy, ataxia, insomnia, somnolence, peripheral sensory and motor (e.g. paralysis) neuropathies, polyneuropathy. Rarely, myelodysplastic syndrome, hepatic, renal, and cardiac failures, atrial fibrillation, hypereosinophilia, severe neurotoxicity.
Potentially Fatal: Serious infections (e.g. pneumonia, septicaemia, septic shock). Rarely, tumour lysis syndrome.

IV/Parenteral/SC: D

May impair ability to drive or operate machinery.

Perform peripheral blood counts regularly during the 1st 4-8 wk post-treatment. Closely monitor for fever, infection, and neurotoxicity. Monitor cardiac, hepatic, and renal function regularly.

Symptoms: Neurotoxicity (e.g. irreversible paraparesis/quadraparesis), acute nephrotoxicity, severe myelosuppession (e.g. neutropenia, anaemia, thrombocytopenia, leukopenia, agranulocytosis), nausea, vomiting, diarrhoea, Guillain Barre and Brown Sequard syndromes. Management: Supportive treatment.

Reduced effect w/ antiviral agents (e.g. lamivudine). May enhance immunosuppression w/ other myelosuppressive agents. May increase risk of infection w/ live attenuated vaccines. May cause cross-resistance w/ other nucleoside analogues (e.g. fludarabine).

Description: Cladribine is a chlorinated purine nucleoside analogue that is cell-cycle nonspecific. It inhibits ribonucleotide reductase causing an imbalance in triphosphorylated deoxynucleotide (dNTP). This leads to breakage of DNA strands and inhibition of DNA synthesis and repair, particularly of resting and proliferating lymphocytes and monocytes. Additionally, it also results in nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) depletion.
Pharmacokinetics:
Distribution: Extensively distributed and penetrates into the CNS. Volume of distribution: Approx 9 L/kg. Plasma protein binding: Approx 20%.
Metabolism: Phosphorylated w/in cells into 2-chlorodeoxyadenosine-5’-triphosphate (CdATP) by deoxycytidine kinase.
Excretion: Via urine (18%). Elimination half-life: 5.4 hr.

Source: National Center for Biotechnology Information. PubChem Database. Cladribine, CID=20279, https://pubchem.ncbi.nlm.nih.gov/compound/Cladribine (accessed on Jan. 21, 2020)

Store between 2-8°C. Protect from light.

Cytotoxic Chemotherapy

L01BB04 - cladribine ; Belongs to the class of antimetabolites, purine analogues. Used in the treatment of cancer.

Anon. Cladribine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 29/07/2016.

Buckingham R (ed). Cladribine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/07/2016.

Cladribine Injection (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 29/07/2016.

Joint Formulary Committee. Cladribine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/07/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Cladribine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 29/07/2016.