L01DB07 - Mitoxantrone |
Propably not porphyrinogenic |
PNP |
Rationale
No evidence of CYP-metabolism. Mitoxantrone is not listed as a CYP inducer, and only as a weak inhibitor of CYP3A4. No observations of interference with CYP-metabolism of other drugs. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Mitoxantrone is an anthracenedione antineoplastic structurally related to doxorubicin.
Therapeutic characteristics
Mitoxaantrone is used alone or with other agents in the treatment of metastatic breast cancer, non-Hodgkins lymphomas, adult acute myeloid leukaemias, hormone-refractory prostate cancer, liver cancer and ovarian cancer. It is administered intravenously. Common adverse reactions of mitoxantrone that can be confused with an acute porphyric attack are nausea, abdominal pain, obstipation and vomiting. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
The precise metabolic pathways of mitoxantrone have not been determined. Excreted in bile and urine, to large extent un-metabolized. In vitro drug interaction studies have demonstrated that mitoxantrone did not inhibit CYP450 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 across a broad concentration range (Norwegian SPC), however it is listed as a weak inhibitor of CYP3A4 by Zhou (2007). No significant drug interactions have been seen in patients who have received Mitoxantrone for treatment of cancer.
IPNet drug reports
No.
References
- Scientific articles
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- 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
- Drug reference publications
- McEvoy GK, editor. Mitoxantrone. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (06.05.10). #2016
- Sweetman SC, editor. Martindale: The complete drug reference. Mitoxantrone. Pharmaceutical Press 2009. #2018
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Novantrone. #2017
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