Fludarabine


Generic Medicine Info
Indications and Dosage
Intravenous
B cell chronic lymphocytic leukaemia
Adult: 25 mg/m2 daily via bolus inj or infusion over 30 min for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles. Dosage may be adjusted based on evidence of haematologic or non-haematologic toxicity.

Oral
B cell chronic lymphocytic leukaemia
Adult: 40 mg/m2 daily for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles. Dosage may be adjusted based on evidence of haematologic or non-haematologic toxicity.
Renal Impairment
CrCl (mL/min) Dosage
 <30 Contraindicated.
 30-70 Reduce dose by up to 50%.
Reconstitution
Dilute the required dose in 10 mL and 100 mL of NaCl 0.9% soln for inj or dextrose 5% to prepare a soln for bolus inj and infusion, respectively.
Contraindications
Decompensated haemolytic anaemia. Renal impairment (CrCl <30 mL/min). Lactation. Concomitant use w/ pentostatin.
Special Precautions
Patient w/ severe impairment of bone marrow function, immunodeficiency, history of opportunistic infections. Renal (CrCl 30-70 mL/min) and hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Skin cancer (new onset or exacerbation).
Nervous: Agitation, confusion, seizure, insomnia, coma, peripheral neuropathy.
CV: Oedema, angina, CHF, arrhythmia, supraventricular tachycardia, MI, DVT, phlebitis, TIA, aneurysm, chest pain.
GI: Nausea, vomiting, diarrhoea, anorexia, stomatitis, GI bleeding, oesophagitis, constipation, mucositis, dysphagia, pancreatitis.
Resp: Cough, dyspnoea, upper resp infection, pharyngitis, allergic pneumonitis, haemoptysis, bronchitis, hypoxia, interstitial pulmonary infiltrate, sinusitis, epistaxis.
Hepatic: Abnormal LFT, cholelithiasis, hepatic failure, reversible hepatotoxicity.
Genitourinary: UTI, dysuria, haematuria, urinary hesitancy, renal failure, proteinuria.
Musculoskeletal: Arthralgia.
Ophthalmologic: Visual disturbance.
Dermatologic: Skin toxicity (e.g. maculopapular rash).
Potentially Fatal: Myelosuppression (e.g. thrombocytopenia, anaemia, neutropenia), autoimmune phenomena (e.g. haemolytic anaemia, autoimmune thrombocytopenia/thrombocytopenic purpura, Evan syndrome, acquired haemophilia), serious opportunistic infections, progressive multifocal leukoencephalopathy, tumour lysis syndrome, severe pulmonary toxicity. Rarely, neurotoxicity, transfusion-related graft-versus-host disease.
IV/Parenteral/PO: D
Patient Counseling Information
This drug may cause confusion, fatigue and visual disturbances, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC w/ differential and platelet count, serum creatinine and albumin, uric acid, AST, ALT; signs of infection, neurotoxicity and tumour lysis syndrome.
Overdosage
Symptoms: Leukoencephalopathy (including nausea, vomiting, headache, visual disturbances, seizures), optic neuritis, papillitis, somnolence, confusion, agitation, para-/quadriparesis, incontinence, muscle spasm, irreversible CNS toxicity (characterised by delayed blindness, coma), severe thrombocytopenia, neutropenia. Management: Supportive treatment. Blood transfusion may be necessary in managing myelosuppression.
Drug Interactions
Reduced therapeutic effect w/ dipyridamole and other inhibitors of adenosine uptake. Cytarabine may reduce the metabolic activation of fludarabine. May diminish the effect of live vaccines.
Potentially Fatal: Increased risk of severe pulmonary toxicity when used in combination w/ pentostatin.
Action
Description: Fludarabine, a purine antagonist metabolite, is rapidly dephosphorylated to 2-fluoro-ara-A and then converted intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP which inhibits α-DNA polymerase, ribonucleotide reductase, and DNA primase, resulting in inhibition of DNA synthesis leading to cell death.
Pharmacokinetics:
Absorption: Bioavailability: Approx 50-65% (oral). Time to peak plasma concentration: Approx 4 hr.
Distribution: Plasma protein binding: Approx 19-29%.
Metabolism: Fludarabine phosphate is rapidly dephosphorylated in the serum to fludarabine which enters the tumour cells to be rephosphorylated by deoxycytidine kinase enzyme to the active triphosphate derivative.
Excretion: Mainly via urine (40-60%). Terminal elimination half-life: Approx 20 hr.
Chemical Structure

Chemical Structure Image
Fludarabine

Source: National Center for Biotechnology Information. PubChem Database. Fludarabine, CID=657237, https://pubchem.ncbi.nlm.nih.gov/compound/Fludarabine (accessed on Jan. 21, 2020)

Storage
Tab: Store between 15-30°C. IV soln: Store between 2-8°C. Protect from light.
This is a cytotoxic drug. Use appropriate personal protective equipment (e.g. gloves) for receiving, handling, admin and disposal.
ATC Classification
L01BB05 - fludarabine ; Belongs to the class of antimetabolites, purine analogues. Used in the treatment of cancer.
References
Anon. Fludarabine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com . Accessed 08/03/2017.

Buckingham R (ed). Fludarabine Phosphate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2017.

Fludarabine Phosphate Injection, Solution (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/03/2017.

Fludarabine Phosphate Tablet, Film Coated (Antisoma Research Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/03/2017.

Joint Formulary Committee. Fludarabine Phosphate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Fludarabine Phosphate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 07/03/2017.

Disclaimer: This information is independently developed by MIMS based on Fludarabine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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