Fludarabine

Fludarabine Uses, Dosage, Side Effects, Food Interaction and all others data.

Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis leading to cell death. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.

Trade Name Fludarabine
Availability Prescription only
Generic Fludarabine
Fludarabine Other Names Fludarabina, Fludarabine, Fludarabinum
Related Drugs Venclexta, prednisone, methotrexate, dexamethasone, triamcinolone, Decadron, rituximab, carboplatin, fluorouracil, Rituxan
Weight 50mg, 25mg/ml
Type Tablets, Oral, Intravenous, Intravenous Powder For Injection, Intravenous Solution, Injection
Formula C10H12FN5O4
Weight Average: 285.235
Monoisotopic: 285.087332049
Protein binding

19-29%

Groups Approved
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer Accord-UK Ltd
Available Country United Kingdom, United States
Last Updated: September 19, 2023 at 7:00 am
Fludarabine
Fludarabine

Uses

Fludarabine Phosphate is used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen. The safety and effectiveness of Fludarabine Phosphate in previously untreated or non-refractory patients with CLL have not been established.

Fludarabine is also used to associated treatment for these conditions: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma refractory, Refractory Non-Hodgkin's lymphoma

How Fludarabine works

Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

Dosage

Fludarabine dosage

Intravenous (Adult):

Chronic lymphocytic leukaemia:25 mg/m2BSA daily given by bolus inj or by IV infusion over 30 minutes for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles.Oral (Adult):

Chronic lymphocytic leukaemia:40 mg/m2BSA daily for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles.

Side Effects

Fever, chills, cough, dyspnoea, pneumonia; GI disturbances, stomatitis; oedema; tumour lysis syndrome; skin rashes; haemolytic anaemia, haemorrhagic cystitis; neurological disturbances including peripheral neuropathy, agitation, confusion, visual disturbances and coma. Progressive encephalopathy and blindness (high doses).

Precaution

Routine monitoring of blood counts and Hb conc. Monitor for signs of autoimmune haemolytic anaemia; elderly. Avoid contact with skin and eyes; avoid inhalation. Myelosuppression may be cumulative and severe increasing risk of opportunistic infections. Increased risk of tumour lysis syndrome in patients with high tumour burden.

Interaction

Co-administration with pentostatin may lead to pulmonary toxicity. Reduced metabolic activation of fludarabine with cytarabine. Reduced therapeutic efficacy with dipyridamole and other adenosine uptake inhibitors.

Food Interaction

  • Take with or without food. Administration with food delays absorption, but not to a clinically significant extent.

Elimination Route

Bioavailability is 55% following oral administration.

Half Life

20 hours

Clearance

  • 117-145 mL/min [patients with B-cell CLL receiving IV administration of a single dose of 40 mg/m^2.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Renal impairment (CrCl <30 mL/min); decompensated haemolytic anaemia. Pregnancy and lactation. Concomitant use of live vaccines.

Special Warning

Renal Impairment:

  • CrCl 30-70: May reduce the doses by up to 50%
  • Severe impairment: Avoid

Storage Condition

Refrigerate at 2-8° C

Innovators Monograph

You find simplified version here Fludarabine

Fludarabine contains Fludarabine see full prescribing information from innovator Fludarabine Monograph, Fludarabine MSDS, Fludarabine FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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