Duloxetine contraindications

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 use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

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. 

Stress a-Adrenergic agonists Pseudoephedrine (15-60 mg three times a day) with food, water, or milk Pseudoephedrine is first-line therapy for women with no contraindication (notably hypertension) (second-line once duloxetine is approved) Phenylpropanolamine was the preferred agent until its removal from the U.S. market in 2000. 

The optimal approach to the pharmacotherapy of SUI, is unclear. Although not supported by evidence-based medicine, many clinicians will initiate a trial of topical estrogen initially, followed by addition of an a-adrenergic receptor agonist in estrogen nonresponders unless contraindicated. Once duloxetine is approved, it will probably be the drug of choice in SUI, providing that it is tolerated. 

Fluvoxamine is a potent inhibitor of the cytochrome P450 isoenzyme CYPl A2, by which duloxetine is, in part, metabolised. Therefore concurrent use raises duloxetine levels. Although the clinical relevance of the increases in duloxetine levels have not been assessed, the manufacturer considers that the rise with fluvoxamine is so marked that the combination should be avoided. " The UK manufacturers specifically contraindicate concurrent use. - Other SSRIs have minimal effects on this isoenzyme, and would therefore not be expected to interact by this route, but see also paroxetine, below. 

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. ... 

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