Bupropion, drug interactions

Hesse LM, Venkatakrishnan K, Court MH, et al. CYP2B6 mediates the in vitro hydroxyla-tion of bupropion potential drug interactions with other antidepressants. Drug Metab Dispos... 

Case reports have suggested that adding stimulant medications or combining a SSRI and a TCA or bupropion may also be effective (APA, 2000), but these combinations need to be done with caution, given the possibility of drug interactions (e.g., SSRIs cytochrome inhibition leading to toxic TCA levels). Additionally, in adults, the combination of antidepressants and psychotherapy (CBT, IPT) for patients with severe or treatment-resistant depression has been found useful (APA, 2000 Keller et al., 2000). 

Three randomized clinical trials support the efficacy of bupropion in ADHD. The first used doses up to 6 mg/kg (98) the other two used doses of 100 to 300 mg per day in equally divided daily doses spaced at least 6 hours apart ( 99, 100). The concern with bupropion is its seizure risk, which requires that its daily dose stay below 450 mg per day in adults (i.e., approximately 6.5 mg/kg). Virtually no work has been done to determine the plasma concentrations of bupropion and its three active metabolites in children and adolescents. Hence, it is unknown whether a limit of 6.5 mg per kg is also appropriate for children. No data exist as to whether children are more or less sensitive to bupropion in terms of seizure risk at the same drug concentration. Also, little is known about pharmacokinetic drug-drug interactions that could reduce the clearance of bupropion. For these reasons, cautious dosing is advised when prescribing bupropion for children on other medications that can reduce oxidative drug metabolism (see Chapter 3 and Chapter 7 for more details). 

Figure 2 List of precipitants evaluated with the substrates bupropion and efavirenz and which have shown more than 20% effect in in vivo inhibition. Display from the Metabolism and Transport Drug Interaction Database (http //www.druginteractioninfo...

McCollum DL, Greene JL, McGuire DK. Severe sinus bradycardia after initiation of bupropion therapy a probable drug-drug interaction with metoprolol. Cardiovasc Drugs Ther 2004 18 329-30. 

Potential drug-drug interactions of ciclosporin with methylphenidate and amfebutamone (bupropion) have been described (43). 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

Hesse, L. M., Venkatakrishnan, K., Court, M. H., von Moltke, L. L., Duan, S. X., Shader, R. I., and Greenblatt, D. J. (2000) CYP2B6 mediates the in vitro hydroxylation of bupropion potential drug interactions with other antidepressants. Drug Metab. Dispos. 28, 1176-1183. 

Popli AP, Tanquary J, LampareUa V, MasandPS. Bupropion and anticonvulsant drug interactions. Ann Clin Psychiatry (1995) 7, 99-101. 

Drug-drug interactions The inhibitory effect of bupropion on CYP2D6 metabolism has been previously demonstrated in vivo, for example by inhibition of dextromethorphan metabolism (SEDA-30, 20). An in vitro study using desipramine as substrate has suggested that this effect is due to the metabolites erythrohydrobupropion and threohydrobupropion, which were much more potent inhibitors of CYP2D6 than hydroxybupropion or bupropion itself [71 ]. 

Reese MJ, Wurm RM, Muir KT, Generaux GT, St John-Williams L, McConn DJ. An in vitro mechanistic study to elucidate the desipramine/bupropion clinical drug-drug interaction. Drug Metab Dispos 2008 36(7) 1198-201. 

Bupropion Hydrochloride Bupropion interacts with levodopa, nicotine, alcohol, and drugs that affect hepatic metabolic enzymes. It lowers the seizure threshold and potentiates the seizure threshold-lowering effect of other antidepressants.135... 

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