Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIZL6AYJN)
  Drug Name Clopidogrel Drug Info Bupropion Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiplatelet Agents Antidepressants
  Structure

 Mechanism of Clopidogrel-Bupropion Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Clopidogrel Bupropion
      Mechanism CYP450 2B6 inhibitor CYP450 2B6 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2B6
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Structure Sequence
MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFREKYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNRWKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIICSIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQEINAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGTETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFSDLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGALKKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKIPPTYQIRFLPR
Gene Name CYP2B6
Uniprot ID CP2B6_HUMAN
KEGG Pathway hsa:1555
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:21289075, PubMed:12865317). 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). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:21289075, PubMed:12865317). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Bupropion caused by Clopidogrel mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if bupropion is prescribed with clopidogrel. Pharmacologic response to bupropion should be monitored closely whenever clopidogrel is added to or withdrawn from therapy. Based on clinical response, dose adjustments of bupropion may be necessary. Concomitant use with once-daily bupropion hydrochloride 450 mg extended release tablets is not recommended. When bupropion/naltrexone is used for weight loss, some authorities recommend a maximum bupropion dosage of 180 mg per day provided as 1 tablet (bupropion 90 mg/naltrexone 8 mg) twice a day (AU, CA, US). Patients should be advised to contact their physician if they experience symptoms of bupropion toxicity such as agitation, anxiety, tremor, insomnia and seizures, or neuropsychiatric symptoms such as delusions, hallucinations, psychosis, impaired concentration, paranoia and confusion.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "Canadian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Product Information. Aplenzin (buPROPion). sanofi-aventis , Bridgewater, NJ.
5 Product Information. Contrave (buPROPion-naltrexone). Orexigen Therapeutics Inc, La Jolla, CA.
6 Product Information. Forfivo XL (buPROPion (bupropion)). Almatica Pharma Inc, Parsippany, NJ.
7 Product Information. Wellbutrin SR (bupropion). Glaxo Wellcome, Research Triangle Park, NC.
8 Product Information. Wellbutrin XL (buPROPion). GlaxoSmithKline, Philadelphia, PA.
9 Product Information. Zyban (bupropion). Glaxo Wellcome, Research Triangle Park, NC.
10 Richter T, Muerdter TE, Heinkele G, et al. "Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine." J Pharmacol Exp Ther 308 (2004): 189-97. [PMID: 14563790]
11 Turpeinen M, Tolonen A, Uusitalo J, Jalonen J, Pelkonen O, Laine K "Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation." Clin Pharmacol Ther 77 (2005): 553-9. [PMID: 15961986]