L01BC01 - Cytarabine |
Propably not porphyrinogenic |
PNP |
Rationale
Primarily non-CYP metabolizm. Not inhibitor or inducer of CYP3A4 or 2C9 in clinical use. However, side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Cytarabine (cytosine arabinoside) is a synthetic pyrimidine nucleoside analog.
Therapeutic characteristics
Cytarabine is an antimetabolite antineoplastic agent used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Administered intravenously by rapid injection or continuous infusion, or by subcutaneous or intrathecal injection. Common adverse reactions of cytarabine that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea and myalgia. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Cytarabine is metabolized to uridinearbinoside by hepatic, gastrointestinal and leucocyte deaminases. After entry into leucemic cells cytarabine undergoes phosphorylations forming the cytotoxic cytarabine triphosphate. Found to be a substrate of CYP3A4 by Colburn et al (2004), and also found to be an inhibitor of CYP3A4, but the authors determined that the inhibition was not of clinical significance. Baumhakel (2001) found no inhibitory effect of cytarabine on CYP3A4 in human liver microsomes.
Published experience
Used uneventfully in the treatment of acute myelogenous leukemia in AIP woman (Wehmeimer, 1987). Used uneventfully in the treatment of acute lymphoblastic leukemia in PV woman (Samuels, 1984).
References
- Scientific articles
- Baumhäkel M, Kasel D, et al. Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001;39(12):517-28. #1941
- Samuels B, Bezwoda WR, et al. Chemotherapy in porphyria. S Afr Med J. 1984;65(23):924-6. #1924
- Wehmeier A, Fischer JT, et al. Polychemotherapy of acute myelogenous leukemia in a patient with acute intermittent porphyria. Klin Wochenschr. 1987;65(7):338-40. #1936
- Drug reference publications
- DrugBank. Cytarabine. Accessed:09.07.10. #1942
- McEvoy GK, editor. Cytarabine. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (09.07.10). #1943
- Sweetman SC, editor. Martindale: The complete drug reference. Cytarabine. Pharmaceutical Press 2009. #1945
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Cytarabine Pfizer. #1944
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