MAOIs Duloxetine

Duloxetine MAOIs Potential for hypertensive crisis, serotonin syndrome, delirium... 

Many commonly used medications also contain substances that are eliminated by the MAOIs and must not be taken by these patients. The list of medications to be avoided inclndes the narcotic pain reliever meperidine (Demerol), and many over-the-connter cold remedies containing dextromethorphan or pseudoephedrine. Finally, patients taking MAOIs must also avoid medications that elevate serotonin levels. This inclndes certain appetite snppressants and antidepressants including the SSRIs, venlafaxine, duloxetine, mirtazapine, nefazodone, and trazodone. Medications that interact with the MAOIs cannot be taken until at least 2 weeks after the MAOI has been stopped. 

Known hypersensitivity to duloxetine or any ingredient of the product concomitant use in patients taking MAOIs use in patients with uncontrolled narrow-angle glaucoma. 

Drugs that may be affected by duloxetine include drugs extensively metabolized by CYP2D6 (eg, flecainide, phenothiazines, propafenone, tricyclic antidepressants, thioridazine), alcohol, CNS-acting drugs, MAOIs, and drugs highly bound to plasma proteins (eg, warfarin). 

Duloxetine is a moderate inhibitor of the CYP 2D6 enzyme and may increase the levels of other medications that use this enzyme (Table 1-1). Because of the risk of serotonin syndrome, duloxetine should not be combined with MAOIs. Because duloxetine is highly bound to plasma protein, combination with another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse events. 

The SNRIs have relatively fewer CYP450 interactions than the SSRIs. Venlafaxine is a substrate but not an inhibitor of CYP2D6 or other isoenzymes, whereas desvenlafaxine is a minor substrate for CYP3A4. Duloxetine is a moderate inhibitor of CYP2D6 and so may elevate TCA and other CYP2D6 substrate levels. Like all serotonergic antidepressants, SNRIs are contraindicated in combination with MAOIs. 

MAOIs DULOXETINE, VENLAFAXINE Risk of severe hypertensive reactions and of serotonin syndrome > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. Due to impaired metabolism of these amines, there is an accumulation of serotonin and norepinephrine in the brain and at peripheral sites Do not co-administer duloxetine and venlafaxine prior to 14 days after discontinuing an MAOI, and do not co-administer MAOI for 5 days after discontinuing duloxetine, 1 week after venlafaxine... 

Combinations of venlafaxine and MAOIs have been reported to cause or be associated with serotonin syndrome. Hence, such combinations must be considered carefully, if at all. To date, there are no other reported interactions between any of the other SNRIs (i.e. duloxetine and milnacipran) and MAOIs. 

The manufacturers of duloxetine contraindicate the concurrent use of MAOIs because of the theoretical risk of the serotonin syndrome. Similarly they recommend caution with other serotonergic drugs, including the SSRIs, venlafaxine, and tryptophan. Fluvoxamine should not be used with duloxetine, because it markedly increases duloxetine levels. Low-dose paroxetine caused a modest increase in the duloxetine ATJC, and fluoxetine is predicted to interact similarly. 

The manufacturers contraindicate the use of duloxetine with non-seleetive irreversible MAOIs, and for 14 days after diseontinuing an MAOI, and at least 5 days should be allowed after stopping duloxetine before starting an MAOI. This is because of the possible risk of serotonin syndrome. " Although the risk would be lower with selective, reversible MAOIs sueh as moclobemide, the manufacturer still says concurrent use is not reeom-mended. ... 

A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. At least 14 days should pass between discontinuation of an MAOI and initiation of therapy with duloxetine. In addition, at least 5 days after stopping duloxetine should be allowed before switching to an MAOI. 

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