Bupropion Valproate

Bupropion + valproate —> increased plasma valproate concentrations. 

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." ... 

Anticonvulsants Carbamazepine decreases the plasma concentration of bupropion to about 90% even after a single dose of 150 mg of carbamazepine. Long-term administration of valproate (a weak inhibitor of hepatic metabolism) has no effect on bupropion plasma concentration. It has been shown that bupropion does not cause clinically relevant changes in the pharmacokinetics of a single dose of 100 mg of lamotrigine. 

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

Carbamazepine decreases bupropion levels and increases the levels of its active metabolite hydroxybupropion. Phenobarbital and phenytoin are predicted to interact similar. The concurrent use of bupropion and valproate has led to increased levels of valproate and hydroxybupropion, and hallucinations have been reported in patients taking both drugs. Hypomania has been reported in a patient taking bupropion and lamotiigine. 

A study found that the AUC of hydroxybupropion, an active metabolite of bupropion, almost doubled when bupropion was given with valproate at steady-state, but the pharmacokinetics of the parent compound and the two other less active metabolites were unaffected. An increase in valproate levels of almost 30% was seen in another report in one patient. Visual and auditory hallucinations were reported in a patient given bupropion and valproate. The UK manufacturer recommends caution when using drugs which may inhibit bupropion metabolism, such as valproate. As valproate levels may also be increased by bupropion, good monitoring for evidence of increased adverse effects of both drugs would seem appropriate. 

Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, Callahan AM, Hinton ML, Chao J, Post RM Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol (1995) 15, 327-33. 

Filteau M-J, Leblanc J, Lefran9oise S, Demers M-F. Visual and auditory hallucinations with the association of bupropion and valproate. CanJ Psychiaby (2000) 45,198-9. 

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