Paroxetineinteractions

Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of PAXIL 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 Table 6 includes clinically significant drug interactions with PAXIL CR.

Table 6: Clinically Significant Drug Interactions with PAXIL CR Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including PAXIL CR, and MAOIs increases the risk of serotonin syndrome. Intervention PAXIL 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 Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention PAXIL CR is contraindicated in patients taking pimozide or thioridazine. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with PAXIL 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 PAXIL 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 PAXIL CR may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of PAXIL 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 PAXIL CR is highly bound to plasma protein. The concomitant use of PAXIL CR with another drug that is highly bound to plasma protein may increase free concentrations of PAXIL CR or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of PAXIL CR or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact PAXIL CR is a CYP2D6 inhibitor. The concomitant use of PAXIL 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 PAXIL CR use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if PAXIL CR is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with PAXIL 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).