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 Theconcurrentuse of anantiplateletagentoranticoagulant with paroxetine maypotentiate the risk ofbleeding. Intervention Informpatientsofthe increasedrisk of bleedingassociated with the concomitantuse ofparoxetine andantiplateletagentsand anticoagulants. For patients takingwarfarin,carefullymonitor the international normalizedratio. Examples aspirin, clopidogrel, heparin,warfarin Drugs Highly Bound toPlasmaProtein Clinical Impact Paroxetine is highlybound to plasma protein. The concomitant useof paroxetine with another drugthat ishighlyboundto plasma protein may increasefreeconcentrationsofparoxetine or othertightly-bound drugs in plasma. Intervention Monitor foradversereactionsandreducedosageof paroxetine orother protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is a CYP2D6inhibitor. The concomitant use of paroxetine with a CYP2D6substrate may increasetheexposure of the CYP2D6substrate. Intervention Decreasethe dosage of a CYP2D6substrate if neededwith concomitantparoxetine use.Conversely,anincreaseindosageof a CYP2D6substratemay be needed if paroxetine is discontinued. Examples propafenone,flecainide,atomoxetine, desipramine, dextromethorphan,metoprolol,nebivolol,perphenazine,tolterodine,venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use oftamoxifen with paroxetine maylead to reduced plasmaconcentrations ofthe active metabolite (endoxifen)andreducedefficacyoftamoxifen. Intervention Consideruse ofanalternativeantidepressantwithlittle or noCYP2D6 inhibition. Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir withparoxetine significantly decreased plasmalevels of paroxetine. Intervention Anydose adjustment should be guidedbyclinicaleffect (tolerabilityandefficacy). Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine oral suspension 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.