4.4.3.2  Is bupropion an inducer of CYP enzymes?

 

According to the label for WELLBUTRIN SR (extended to the proposed labeling for WELLBUTRIN XL), animal data indicate that bupropion may induce drug-metabolizing enzymes in humans.  There is no evidence that it induces its own metabolism.

 

4.4.3.3  Is the drug a substrate and/or an inhibitor of P-glycoprotein transport processes?

There is no information available about the role of bupropion as a substrate or inhibitor of P-glycoprotein.

 

4.4.3.4  Are there other metabolic/transporter pathways that may be important in the pharmacokinetics of bupropion?

There is no information to address this.

 

4.4.3.5  Does the label specify co-administration of another drug (e.g., combination therapy in oncology) and, if so, has the interaction potential between these drugs been evaluated?

The label does not specify co-administration of another drug.

 

4.4.3.6  What other co-medications are likely to be administered to the target patient population?

Bupropion may be used with other antidepressants such as SSRIs.  It could also be potentially be used as an antidepressant in patients with concomitant disease such as HIV (includes medications such as ritonavir, efavirenz, and nelfinavir) or cancer (medications include cyclophosphamide, a CYP2B6 substrate and thiotepa, a CYP2B6 inhibitor.

 

4.4.3.7  Are there any in vivo drug-drug interaction studies that indicate the exposure alone and/or exposure-response relationships are different when drugs are co-administered?

According to the label for WELLBUTRIN SR (extended to the proposed labeling for WELLBUTRIN XL), after concomitant administration of 800 mg cimetidine with bupropion (two 150 mg tablets of WELLBUTRIN SR) in healthy volunteers the pharmacokinetics of bupropion and hydroxybupropion were unaffected, although there were 16% and 32% increases in AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.  A dosage adjustment has not been recommended regarding concomitant administration of cimetidine and bupropion.

 

According to the label for WELLBUTRIN SR (extended to the proposed labeling for WELLBUTRIN XL), the effects of bupropion on desipramine (a CYP2D6 substrate) pharmacokinetics were evaluated in healthy volunteers.  An increase of C_max, AUC, and t_1/2 of desipramine of 2-, 5-, and 2-fold, respectively was observed.  The label suggests that co-administration of bupropion with drugs that are metabolized by CYP2D6 should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication, and that if bupropion is added to a regimen containing a substrate of CYP2D6, the need to decrease the dose of the original medication should be considered.

 

 

16

 

 

 

Back a Page
Next Page
Back to Wellbutrin XL NDA Index Page
Back to Main Index Page