L01EA01 - Imatinib |
Propably not porphyrinogenic |
PNP |
Rationale
Imatinib is a competative inhibitor of CYP3A4 and 2C9, but there is no data pointing to capacity for mechanism-based inhibition, nor to induction of metabolism of CYP3A4 or 2C9 substrates. Not listed as CYP inducer or irreversible CYP-inhibitor. However, side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Imatinib is an inhibitor of Bcr-Abl tyrosine kinase. The polycyclic molecule contains a secondary amino function.
Therapeutic characteristics
Imatinib is an antineoplastic agents used to treat chronic myelogenous leukemia, malignant gastrointestinal stromal tumors and in dermatofibrosarcoma. It is administered orally. Common adverse reactions of imatinib that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea, abdominal pain, paraesthesia, myalgia, arthalgia and insomnia. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Imatinib is mainly metabolized by CYP 3A4, while CYPs 1A2, 2D6, 2C9 and 2C19 play lesser roles. Main metabolite is the N-demetylated piperazinederivative. It is a relatively strong competetive inhibitior of of CYPs 3A4/5, 2C9 and 2D6. Imatinib did not exert a significant effect on the PXR-mediated induction of CYP3A4 (Harmsen, 2009). Not listed as CYP inducer or irreversible inhibitor.
References
- Scientific articles
- Zhou, S.F., Xue, C.C., et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007; 29(6):687:710. #1027
- Harmsen S, Meijerman I, et al. Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009;64(1):35-43. PMID 18839173. #4573
- Drug reference publications
- McEvoy GK, editor. Imatinib. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (03.06.10). #2056
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Glivec. #2057
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