Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIQ47ZJXI)
Drug Name			Chlorpheniramine		Drug Info		Bupropion		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiallergic Agents				Antidepressants
Structure

Mechanism of Chlorpheniramine-Bupropion Interaction (Severity Level: Moderate)
CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Chlorpheniramine				Bupropion
Mechanism		CYP450 2D6 substrate				CYP450 2D6 inhibitor
Key Mechanism Factor 1
		Factor Name		Cytochrome P450 2D6				× Structure Sequence MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
		Gene Name		CYP2D6
		Uniprot ID		CP2D6_HUMAN
		KEGG Pathway		hsa:1565
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). 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:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Click to Show/Hide
Mechanism Description		Decreased metabolism of Chlorpheniramine caused by Bupropion mediated inhibition of CYP450 enzyme

Recommended Action
Management		Caution is advised if bupropion must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Concomitant medications should be initiated at the lower end of the dose range. Clinical and laboratory monitoring may be appropriate for some drugs whenever bupropion is added to or withdrawn from therapy.

References
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3	Guzey C, Norstrom A, Spigset O "Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion." Ther Drug Monit 24 (2002): 436-7. [PMID: 12021638]
4	James WA, Lippmann S "Bupropion: overview and prescribing guidelines in depression." South Med J 84 (1991): 222-4. [PMID: 1899294]
5	Product Information. Aplenzin (buPROPion). sanofi-aventis , Bridgewater, NJ.
6	Product Information. Wellbutrin (bupropion). Glaxo Wellcome, Research Triangle Park, NC.
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	Shad MU "A possible bupropion and imipramine interaction." J Clin Psychopharmacol 17 (1997): 118. [PMID: 10950476]
11	Shin YW, Erm TM, Choi EJ, Kim SY "A Case of Prolonged Seizure Activity After Combined Use of Bupropion and Clomipramine." Clin Neuropharmacol 27 (2004): 192-194. [PMID: 15319707]