L01BB05 - Fludarabine |
Propably not porphyrinogenic |
PNP |
Rationale
Non-CYP metabolism. Side effects such as nausea, vomiting and anorexia may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Fluorinated nucleotide analogue administered as phosphate, slightly soluble in water.
Therapeutic characteristics
Fludarabine is an antimetabolite antineoplastic agent used to treat chronic lymphatic leucemia of B-cell type in patients with sufficient bone marrow reserve. Administered orally or as an infusion. Common adverse reactions of fludarabine that can be confused with an acute porphyric attack are nausea, vomiting and peripheral neuropathy common. Side effects such as nausea, vomiting and anorexia may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Fludarabine phosphate is rapidly dephosphorylated followed by selective distribution to leucemic cells, whereit is rephosphorylated to the active triphosphate nucleotide. This is eliminated from target cells with a half life of about 23 hours. The active metabolite F-ara-A formed on dephosphorylation of fludarabine is largely eliminatd by renal excretion (Ganhi et al, 2002). Not reported by Rendic (2002) as CYP-inductor or inhibitor.
IPNet drug reports
No.
References
- Scientific articles
- Gandhi, V., Plunkett, W. Cellular and Clinical Pharmacology of Fludarabine. Clin Pharmacokinet 2002; 41(2): 93-103. PMID 11888330. #4570
- Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. PMID 11996015. #4559
- Drug reference publications
- McEvoy GK, editor. Fludarabine. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (03.12.09). #3328
- Sweetman SC, editor. Martindale: The complete drug reference. Fludarabine. Pharmaceutical Press 2009. #3330
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). FLUDARA. #3329
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