Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIEQ0TJBC)
  Drug Name Imipramine Drug Info Armodafinil Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Cns Stimulants
  Structure

 Mechanism of Imipramine-Armodafinil Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Imipramine Armodafinil
      Mechanism CYP450 2C19 substrate CYP450 2C19 inhibitor
      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 Imipramine caused by Armodafinil mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if tricyclic antidepressants are coadministered with modafinil or armodafinil in CYP450 2D6-deficient patients. Pharmacologic effects and serum TCA levels should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy, and the TCA dosage adjusted accordingly. Patients should be advised to notify their physician if they experience possible signs of TCA toxicity such as excessive drowsiness, restlessness, agitation, ataxia, blurred vision, tachycardia, arrhythmia, and seizures.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Grozinger M, Hartter S, Hiemke C, Griese EU, Roschke J "Interaction of modafinil and clomipramine as comedication in a narcoleptic patient." Clin Neuropharmacol 21 (1998): 127-9. [PMID: 9579300]
3 Product Information. Nuvigil (armodafinil). Cephalon Inc, West Chester, PA.
4 Product Information. Provigil (modafinil). Cephalon, Inc, West Chester, PA.
5 Robertson P, Decory HH, Madan A, Parkinson A "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos 28 (2000): 664-71. [PMID: 10820139]