Ketoconazole reboxetine

Reboxetine is metabolized by CYP3A4. In 11 healthy volunteers ketoconazole, an inhibitor of CYP3A4, increased the plasma AUC of reboxetine by about 50% and prolonged the half-life (7). The adverse effects profile of reboxetine was not altered by ketoconazole, but the... 

Herman BD, Fleishaker JC, Brown MT. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999 66(4) 374-9. 

Fleishaker JC, Herman BD, Pearsotr LK, lorrita A, Mucci M. Evaluation of the potential pharmacokinetic/pharmaco-dynamic interaction between fluoxetine and reboxetine in healthy volunteers. Clin Drug Invest 1999 18 141-50. Herman BD, Fleishaker 1C, Brown MT. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999 66(4) 374-9. 

Clinically important, potentially hazardous interactions with astemizole, atorvastatin, cyclosporine, fluvastatin, glibenclamide, glyburide, itraconazole, ketoconazole, lovastatin, oral contraceptives, reboxetine, simvastatin, St John s wort,... 

Ketoconazole may inhibit the metabolism of reboxetine. The manufacturer therefore advises avoiding the concurrent use of azoles, macrolides and nefazodone. 

A study in 11 healthy subjects found that ketoconazole 200 mg daily for 5 days increased the plasma coneentrations of a single 4-mg dose of reboxetine, taken on the second day, by about 50%. Although the adverse effeet profile of reboxetine was not altered, beeause reboxetine has a narrow therapeutic index it was coneluded that eaution should be used and a reduetion in reboxetine dosage eonsidered if it is given with ketoconazole. The manufacturer recommends that potent inhibitors of CYP3A4, ineluding azoles, macrolides (erythromycin) and nefazodone should not... 

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