CYP3A4 inhibitors Reboxetine

The manufacturer of reboxetine recommends avoiding the concurrent use of potent CYP3A4 inhibitors as reboxetine levels may be increased. They also recommend avoiding the concurrent use of MAOk, because of the possible risk of hypertensive crises. The concurrent use of fluoxetine and reboxetine does not appear to alter the pharmacokinetics of either drug. 

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... 

In addition, reboxetine was found to be a weak in vitro inhibitor of the activity of CYP2D6 and CYP3A4. The inhibitory effect of reboxetine on CYP2D6 and CYP3A4 is unlikely to be relevant in vivo because it occurs at concentrations well above those achieved clinically. 

The manufacturer of reboxetine suggests that because fluvoxamine is a potent inhibitor of CYP3A4 it may increase plasma concentrations of reboxetine, and, because of the narrow therapeutic margin of reboxetine, concurrent use should be avoided. However, note that fluvoxamine is more usually considered a potent inhibitor of CYP1A2 and is generally considered a weak inhibitor of CYP3A4. 

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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