Fluvoxamine Reboxetine

FLUVOXAMINE REBOXETINE May t fluvoxamine levels Reboxetine Is a selective norepinephrine reuptake inhibitor. Reboxetine inhibits metabolism of fluvoxamine Avoid concurrent use (manufacturers recommendation)... 

The potency of sertraline and its N-demethylated metabolite, desmethylsertraline, and paroxetine for inhibiting P-gp was comparable with that of quinidine (35). Fluoxetine, norfluoxetine, fluvoxamine, reboxetine, and 0-demethylparoxetine showed intermediate inhibition, and citalopram, desmethylcitalopram, venlafaxine, and N-desmethylvenlafaxine showed only weak inhibition. No inhibition was found for 0-desmethylvenlafaxine. 

Because reboxetine and bupropion share with desipramine the ability to block the NE uptake pump, some clinician may want to combine them with an SSRI. Bupropion, however, should be used cautiously with fluvoxamine, fluoxetine, and paroxetine because these three antidepressants inhibit one or more CYP enzymes to a substantial degree at their lowest, usually effective antidepressant dose. Therefore, the dose of bupropion should be kept low and TDM could be used to ensure that unusually high levels of bupropion or its active metabolites do not develop. 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

Reboxetine Reboxetine should not be given, even after termination of MAOI therapy. Care must be exercised when treating with antihypertensive drugs, antiar-rhythmics, cyclosporin, antipsychotics, tricyclics, fluvoxamine, antidepressants, azole antifungals, and macrolide antibacterials. 

In the 1980s an entirely new class of antidepressant arrived with the SSRIs, firstly fluvoxamine immediately followed by fluoxetine (Prozac). Within 10 years, the SSRI class accounted for half of antidepressant prescriptions in the United Kingdom. Further developments in the evolution of the antidepressants have been novel compounds such as venlafaxine, reboxetine, nefazodone and mirtazapine, and a reversible monoamine oxidase inhibitor, moclobemide. 

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 (5). The adverse effects profile of reboxetine was not altered by ketoconazole, but the finding suggests that reboxetine should be used with caution in combination with drugs that inhibit CYP3A4, for example nefazodone and fluvoxamine. 

Figure 8. Structures of the SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), the NSRI reboxetine, and the SNRI venlafaxine.

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. 

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