Basic Information
ID DDInter1159 and DDInter252
Interaction The use of bupropion is associated with a dose-related risk of seizures. The risk may be further increased when coadministered with other agents that can reduce the seizure threshold, including antidepressants, CNS stimulants, acetylcholinesterase inhibitors, phenothiazines, and dopaminergic blocking agents such as neuroleptics and metoclopramide. Coadministration with bupropion may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6, including many antidepressants, neuroleptics, CNS stimulants (e.g., amphetamines), metoclopramide, and some acetylcholinesterase inhibitors (e.g., donepezil, galantamine). The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by bupropion and its metabolite, hydroxybupropion.
Management Extreme caution is advised if bupropion is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as concomitant medications should be initiated at the lower end of the dosage range and titrated gradually as needed and as tolerated. The maximum recommended dosage for the specific bupropion formulation should not be exceeded.
References [1] Johnston JA, Lineberry CG, Ascher JA, et al. "A 102-center prospective study of seizure in association with bupropion." J Clin Psychiatry 52 (1991): 450-6 [2] 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 [3] James WA, Lippmann S "Bupropion: overview and prescribing guidelines in depression." South Med J 84 (1991): 222-4 [4] Sheehan DV, Welch JB, Fishman SM "A case of bupropion-induced seizure." J Nerv Ment Dis 174 (1986): 496-8 [5] Storrow AB "Bupropion overdose and seizure." Am J Emerg Med 12 (1994): 183-4 [6] Shad MU "A possible bupropion and imipramine interaction." J Clin Psychopharmacol 17 (1997): 118 [7] Masco HL, Kiev A, Holloman LC, Batey SR, Johnston JA, Lineberry CG "Safety and efficacy of bupropion and nortriptyline in outpatients with depression." Curr Ther Res Clin Exp 55 (1994): 851-63 [8] "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [9] Dufresne RL, Weber SS, Becker RE "Bupropion hydrochloride." Drug Intell Clin Pharm 18 (1984): 957-64 [10] "Product Information. Zyban (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [11] Gittelman DK, Kirby MG "A seizure following bupropion overdose." J Clin Psychiatry 54 (1993): 162 [12] Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink." [13] Enns MW "Seizure during combination of trimipramine and bupropion." J Clin Psychiatry 62 (2001): 476-7 [14] Rosenstein DL, Nelson JC, Jacobs SC "Seizures associated with antidepressants: a review." J Clin Psychiatry 54 (1993): 289-99 [15] 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 [16] "Product Information. Aplenzin (buPROPion)." sanofi-aventis , Bridgewater, NJ. [17] Pisani F, Spina E, Oteri G "Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice." Epilepsia 40(Suppl 10) (1999): S48-56 [18] "Product Information. Wellbutrin XL (buPROPion)." GlaxoSmithKline, Philadelphia, PA. [19] "Product Information. Wellbutrin SR (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [20] "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [21] Posner J, Bye A, Jeal S, Peck AW, Whiteman P "Alcohol and bupropion pharmacokinetics in healthy male volunteers." Eur J Clin Pharmacol 26 (1984): 627-30 [22] Hamilton MJ, Bush MS, Peck AW "The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man." Eur J Clin Pharmacol 27 (1984): 75-80 [23] Ramcharitar V, Levine BS, Goldberger BA, Caplan YH "Bupropion and alcohol fatal intoxication: case report." Forensic Sci Int 56 (1992): 151-6
Alternative for Mesoridazine N05A
Amisulpride Droperidol Pimavanserin
Alternative for Bupropion A08A
Orlistat Naltrexone Dexfenfluramine

N06A
Tryptophan Fluvoxamine Oxitriptan Viloxazine Vilazodone Vortioxetine
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.