Fludarabine

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Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Adverse-effects 6 Mechanism-of-action 7 More General Terms 8 Additional Terms 9 Internet Database 10 References

Introduction

• Tradename: Fludara. Fludarabine phosphate. (9-b-beta-arabinofuranosyl-2-fluoroadenine)

Indications

• treatment of chronic lymphocytic leukemia ( B-cell) in patients not responding to other agents
• low grade, non-Hodgkin's lymphoma ( follicular lymphoma)

Dosage

• 25 mg/m2/day IV for 5 days every 4 weeks
• 30% reduction if creatinine clearance < 70 mL/min

• Lyophilized powder for injection: 50 mg
• Refrigerate: use within 8 hours of reconstitution.

Pharmacokinetics

• metabolized to 2 active metabolites
• highly tissue bound
• eliminated mostly in the urine
• 1/2life is 10 hours
  

• elimination via kidney
• 1/2life = 10 hours

Adverse-effects

• common (> 10%)

• nausea/vomiting: mild emetic
• fever/ chills, fatigue, pain, rash, diarrhea, stomatitis, GI bleeding, urinary tract infection, paresthesia, myalgia, weakness, dyspnea, non-productive cough, pneumonitis, pneumonia, infection
• myelosuppression

• nadir:

• neutrophils: 3-25, mean: 13 days
• platelets: 2-32, mean: 16 days
• WBC: 8 days

• recovery 5-7 weeks

• less common (1-10%)

• congestive heart failure, malaise, headache, alopecia, hyperglycemia, anorexia, hearing loss

• uncommon (< 1%)

• occur with higher doses, often occurs on rechallenge. generally accompanied by CNS demyelination
• steroid treatment my or may not be helpful
• somnolence, blindness, coma, death, severe neurotoxicity, skin rash, metabolic acidosis, metallic taste, autoimmune hemolytic anemia (may be fatal), reversible hepatotoxicity, renal failure, hematuria, tumor lysis syndrome

• other [3]

• peripheral neuropathy
• delayed demyelinating CNS syndromes

Mechanism-of-action

• antimetabolite
• interferes with DNA synthesis

More General Terms

• antineoplastic agent (chemotherapeutic agent)
• antimetabolite

Additional Terms

• chronic lymphocytic leukemia (CLL)

Internet Database

PubChem: 657237
PubChem: 3368
PubChem: 30751
PubChem: 3367

References

1. Kaiser Permanente Northern California Regional Drug Formulary, 1998
2. AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1998
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529

fludarabine (Fludara)