L01CD02 - Docetaxel |
Propably not porphyrinogenic |
PNP |
Rationale
Human PXR-activator of low or medium potency, most likely limited capacity for significant CYP-induction. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Docetaxel is a semisynthetic taxane similiar to paclitaxel, manufactured from a taxane precursor derived from the needles of the European yew tree. Taxus baccata.
Therapeutic characteristics
Docetaxel is an antineoplastic agent used alone or in combination with other cytostatics in the treatment of cancers such as breast cancer, lung cancer, and prostate cancer. It is administered as an intravenous infusion. Common adverse reactions of docetaxel that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea/obstipation, abdominal pain, myalgia, peripheral sensoric and/or motoric neuropathy. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Docetaxel is extensively metabolized via CYP3A4. Synold (2001) found that docetaxel did not activate human PXR. In another study docetaxel was observed to moderately activate PXR, but there was no significant induction of CYP3A4 observed in human administration (Harmsen, 2009). Zhou (2007) reports docetaxel as a weak inhibitor of CYP 3A4. Interactions with CYP metabolism of other drugs in clinical use are not systematically studied.
Published experience
Docetaxel is used uneventfully to treat breast cancer in 2 women with VP, and used uneventfully to treat cancer of the uterus in one woman with AIP (Thiery-Vuillemin, 2008).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
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
- Thiery-Vuillemin, A, Chaigneau, L, et al. Anticancer therapy in patients with porphyrias: evidence today. Expert Opin Drug Saf 2008; 7(2):159-165. #1989
- Zhou, S.F., Xue, C.C., et al. Clinicallay 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. #1957
- 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
- Synold TW, Dussault I, et al. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 2001;7(5):584-90. PMID 11329060. #4575
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Docetaxel. Pharmaceutical Press 2009. #1988
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Taxotere. #1987
Similar drugs
© NAPOS 2024