Drug interactions duloxetine

Several antidepressants, including most of the SSRIs, nefa-zodone, and duloxetine, are known to inhibit various cytochrome P-450 isoenzymes, thereby elevating plasma levels of substrates for those isoenzymes and thus potentially leading to increased adverse effects or toxicity of those drugs. The propensity to cause these drug interactions will vary with the particular antidepressant and the precise isoenzyme9,19,30 (Table 35-6). 

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. 

Not altered in advanced age, mild to moderate renal impairment, mild hepatic impairment (Child-Pugh A). Sign, altered in severe renal disease and moderate hepatic impairment (Child-Pugh B) Systemic exposure to duloxetine decreased by V3 in smokers (dose change not recommended) Multiple drug-drug interactions possible with CYP4502D6 and 1A2 substrates/ inhibitors... 

To avoid drug interactions, clinicians should be careful when administering duloxetine with substrates or inhibitors of cytochrome P450 (CYP450) isoenzymes 2D6 and 1A2. 

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... 

ST JOHN S WORT DULOXETINE t risk of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive effect Avoid co-administration... 

ST JOHN S WORT SSRIs t risk of serotonin syndrome For signs and symptoms of serotonin toxicity, see Qinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive effect. In addition, TCAs inhibit CYP2D6-mediated metabolism of SSRIs Caution with co-administration with TCAs or trazodone. Specialist advice should be sought and alternatives considered. Avoid co-administration of two SSRIs, and SSRIs with duloxetine or St John s wort... 

It is an empirical decision whether to start with duloxetine or anti-epileptics for neuropathic pain management. Vigilant follow-up and patient education on drug-drug interactions are crucial to a successful launch of duloxetine. It is prudent to start with a low dose (20-30 mg) of duloxetine and titrate cautiously to balance the risk and benefit ratio. Duloxetine doses higher than 60 mg failed to provide any additional pain relief yet caused more adverse events and withdrawals according to previous clinical studies. 

Drug-drug interactions Desvenlafaxine has been reported to have minimal effect on CYP2D6 in a comparison with duloxetine, a moderate inhibitor of CYP2D6, in a randomized, open, crossover study in healthy... 

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. 

Duloxetine markedly increased the AUC of desipramine other tricyclics metabolised by CYP2D6 are expected to interact similarly. Note that the use of duloxetine with other serotonergic drugs such as the tricyclics should be undertaken with caution or avoided because of the theoretical increased risk of serotonin syndrome. 

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