Paroxetineinteractions

Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of Paroxetine HCL CR 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.

7.1 Clinically

Significant Drug Interactions with Paroxetine HCL CR Table 6 includes clinically significant drug interactions with Paroxetine HCL CR.

Table 6: Clinically Significant Drug Interactions with Paroxetine HCL CR Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including Paroxetine HCL CR, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine HCL CR 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 Paroxetine HCL CR should not be used in patients receiving medications that can prolong QT interval and are metabolized by CYP450 2D6 such as thioridazine or pimozide (see Contraindications and Warnings and Precautions ) Intervention Paroxetine HCL CR is contraindicated in patients taking pimozide or thioridazine. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with Paroxetine HCL CR 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 HCL CR and/or concomitant serotonergic drugs. Examples Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, 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 HCL CR may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of Paroxetine HCL CR 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 HCL CR is highly bound to plasma protein. The concomitant use of Paroxetine HCL CR with another drug that is highly bound to plasma protein may increase free concentrations of Paroxetine HCL CR or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of Paroxetine HCL CR or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine HCL CR is a CYP2D6 inhibitor. The concomitant use of Paroxetine HCL CR 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 HCL CR use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Paroxetine HCL CR is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with Paroxetine HCL CR may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant 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).