L01XA02 - Carboplatin |
Not porphyrinogenic |
NP |
Rationale
Non-CYP metabolism. However, side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Carboplatin is a platinum coordination compound composed of a platinum atom surrounded in a plane by 2 ammonia groups and 2 other ligands in the cis position(diaminocyclobutane dicarboxy platinium).
Therapeutic characteristics
Carboplatin is a platinum-containing antineoplastic agent used in the treatment of ovarian tumours, lung cancer and certain head and neck cancers.
It is administered as an intravenous infusion. Common adverse reactions of carboplatin that can be confused with an acute porphyric attack are vomiting, nausea, GI pain, and constipation. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Carboplatin is mainly excreted unchanged by the kidneys. Partly non-enzymatically degraded. No reports of drug interactions pointing to CYP-metabolism.
Not listed by Rendic (2002) as CYP-inducer or inhibitor. Carboplatin did not exert a significant effect on the PXR-mediated induction of CYP3A4 (Harmsen, 2009). Carboplatin was without inhibitory effect on CYP3A4 (Baumhakel, 2001).
Published experience
Used uneventfully in AIP woman in the treatment of squamous cell carcinoma of the uterus (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
- 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 Dec;39(12):517-28. #2019
- 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.Carboplatin. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (10.05.10). #2028
- Sweetman SC, editor. Martindale: The complete drug reference. Carboplatin. Pharmaceutical Press 2009. #2029
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