Venlafaxine CYP2D6 substrates

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. 

No important interactions normally appear to occur with venlafaxine and ACE inhibitors, beta blockers or diuretics, but an isolated report suggests that propranolol, particularly if it is given with other CYP2D6 substrates, may affect the metabolism of venlafaxine. 

Theoretically the metabolism of venlafaxine may be inhibited by CYP2D6 inhibitors or substrates such as diphenhydramine, melperone, quinidine or thioridazine. CYP3A4 inhibitors such as ketoconazole may also have some effect. An isolated case describes a hypertensive crisis associated with venlafaxine and di-sulfiram. The manufacturers predict that the use of triptans with venlafaxine may have additive effects on serotonin, which could lead to the serotonin syndrome. 

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