Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIMCUERD5)
  Drug Name Letrozole Drug Info Cilostazol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Vasodilator Agents
  Structure

 Mechanism of Letrozole-Cilostazol Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Letrozole Cilostazol
      Mechanism CYP450 2C19 inhibitor CYP450 2C19 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C19
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Structure Sequence
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C19
Uniprot ID CP2CJ_HUMAN
KEGG Pathway hsa:1557
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
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      Mechanism Description
  • Decreased metabolism of Cilostazol caused by Letrozole mediated inhibition of CYP450 enzyme

Recommended Action
      Management Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 and/or 2C19 inhibitor is added to or withdrawn from cilostazol therapy, and the dosage adjusted as necessary. Patients should be advised to contact their physician if they experience adverse effects of cilostazol such as dizziness, nausea, diarrhea, bleeding, or irregular heartbeat.

References
1 Hedaya MA, El-Afify DR, El-Maghraby GM "The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers." Biopharm Drug Dispos 27 (2006): 103-10. [PMID: 16372380]
2 Herrlin K, Segerdahl M, Gustafsson LL, Kalso E "Methadone, ciprofloxacin, and adverse drug reactions." Lancet 356 (2000): 2069-70. [PMID: 11145498]
3 McLellan RA, Drobitch RK, Monshouwer M, Renton KW "Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human." Drug Metab Dispos 24 (1996): 1134-8. [PMID: 8894516]
4 Product Information. Pletal (cilostazol). Otsuka American Pharmaceuticals, Rockville, MD.
5 Sawant RD "Rhabdomyolysis due to an uncommon interaction of ciprofloxacin with simvastatin." Can J Clin Pharmacol 16 (2009): e78-9. [PMID: 19151423]
6 Shahzadi A, Javed I, Aslam B, et al. "Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers." Pak J Pharm Sci 24 (2011): 63-8. [PMID: 21190921]
7 Sriwiriyajan S, Samaeng M, Ridtitid W, Mahatthanatrakul W, Wongnawa M "Pharmacokinetic interactions between ciprofloxacin and itraconazole in healthy male volunteers." Biopharm Drug Dispos 32 (2011): 168-74. [PMID: 21360715]
8 Suri A, Bramer SL "Effect of omeprazole on the metabolism of cilostazol." Clin Pharmacokinet 37 (1999): 53-9. [PMID: 10702887]
9 Suri A, Forbes WP, Bramer SL "Effects of CYP3A inhibition on the metabolism of cilostazol." Clin Pharmacokinet 37 (1999): 61-8. [PMID: 10702888]