371 Laboratory Tests: There are no specific laboratory tests recommended.
372 Drug Interactions: Few systemic data have been collected on the metabolism of bupropion
373 following concomitant administration with other drugs or, alternatively, the effect of
374 concomitant administration of bupropion on the metabolism of other drugs.
375 Because bupropion is extensively metabolized, the coadministration of other drugs may affect
376 its clinical activity. In vitro studies indicate that bupropion is primarily metabolized to
377 hydroxybupropion by CYP2B6 isoenzyme. Therefore, the potential exists for a drug
378 interaction between WELLBUTRIN XL and drugs that are substrates or inhibitors of the
379 CYP2B6 isoenzyme (e.g., orphenadrine, thiotepa, cyclophosphamide). In addition, in vitro
380 studies suggest that paroxetine, sertraline, norfluoxetine, and fluvoxamine as well as nelfinavir,
381 ritonavir, and efavirenz inhibit the hydroxylation of bupropion. No clinical studies have been
382 performed to evaluate this finding. The threohydrobupropion metabolite of bupropion does not
383 appear to be produced by the cytochrome P450 isoenzymes. The effects of concomitant
384 administration of cimetidine on the pharmacokinetics of bupropion and its active metabolites
385 were studied in 24 healthy young male volunteers. Following oral administration of two 150-mg
386 tablets of the sustained-release formulation of bupropion with and without 800 mg of cimetidine,
387 the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were
388 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of
389 threohydrobupropion and erythrohydrobupropion.
390 While not systematically studied, certain drugs may induce the metabolism of bupropion (e.g.,
391 carbamazepine, Phenobarbital, phenytoin).
392 Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in
393 humans. In one study, following chronic administration of bupropion, 100 mg 3 times daily to
394 8 healthy male volunteers for 14 days, there was no evidence of induction of its own metabolism.
395 Nevertheless, there may be the potential for clinically important alterations of blood levels of
396 coadministered drugs.
397 Drugs Metabolized by Cytochrome P450IID6 (CYP2D6): Many drugs, including most
398 antidepressants (SSRIs, many tricyclics), beta-blockers, antiarrhythmics, and antipsychotics are
399 metabolized by the CYP2D6 isoenzyme. Although bupropion is not metabolized by this
400 isoenzyme, bupropion and hydroxybupropion are inhibitors of CYP2D6 isoenzyme in vitro. In a
401 study of 15 male subjects (aged 19 to 35 years) who were extensive metabolizers of the CYP2D6
402 isoenzyme, daily doses of bupropion given as 150 mg twice daily followed by a single dose of
403 50 mg desipramine increased the Cmax, AUC, and t1/2 of desipramine by an average of
404 approximately 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the
405 last dose of bupropion. Concomitant use of bupropion with other drugs metabolized by CYP2D6
406 has not been formally studied.
407 Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6
408 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine,
409 paroxetine, fluvoxamine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine)
410 beta-blockers (e.g., metoprolol), and Type1C antiarrhythmics (e.g., propafenone, flecainide),
11
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