Paroxetineinteractions

Table 9 presents clinically significant drug interactions with paroxetine. Table 9 Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue. Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs. Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines and St. John's Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is a CYP2D6 inhibitor. The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy). Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted.

Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted.

Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition.