Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDINAP28DX)
  Drug Name Paclitaxel (protein-bound) Drug Info Deferasirox Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics/Mitotic Inhibitors Chelating Agents
  Structure

 Mechanism of Paclitaxel (protein-bound)-Deferasirox Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Paclitaxel (protein-bound) Deferasirox
      Mechanism CYP450 2C8 substrate CYP450 2C8 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C8
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Structure Sequence
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRWKEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV
Gene Name CYP2C8
Uniprot ID CP2C8_HUMAN
KEGG Pathway hsa:1558
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
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      Mechanism Description
  • Decreased metabolism of Paclitaxel (protein-bound) caused by Deferasirox mediated inhibition of CYP450 enzyme

Recommended Action
      Management Clinicians should consider the potential for interaction with drugs that inhibit CYP450 2C8 and/or 3A4 and monitor for evidence of dose-related toxicities of paclitaxel during coadministration, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy.

References
1 Bergmann TK, Filppula AM, Launiainen T, Nielsen F, Backman J, Brosen K "Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma." Br J Clin Pharmacol (2015):. [PMID: 26446447]
2 Bun SS, Ciccolini J, Bun H, Aubert C, Catalin J "Drug interactions of paclitaxel metabolism in human liver microsomes." J Chemother 15 (2003): 266-74. [PMID: 12868554]
3 Cerner Multum, Inc. "Australian Product Information.".