(see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.sodium sulfate/potassium sulfate/magnesium sulfateMonitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases effects of paroxetine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using bowel preps together with drugs that lower the seizure threshold.sotalolSerious - Use Alternative (1)paroxetine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.St John's WortSerious - Use Alternative (1)paroxetine and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.sufentanilSerious - Use Alternative (1)sufentanil, paroxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.sufentanil SLMonitor Closely (1)sufentanil SL, paroxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.sulfamethoxazoleMonitor Closely (1)sulfamethoxazole and paroxetine both increase QTc interval. Use Caution/Monitor.sulfasalazineMonitor Closely (1)paroxetine, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.sulindacMonitor Closely (1)paroxetine, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.sumatriptanMonitor Closely (1)sumatriptan and paroxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)paroxetine, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.sumatriptan intranasalMonitor Closely (1)sumatriptan intranasal and paroxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)paroxetine, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.tamoxifenMonitor Closely (1)paroxetine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.tamsulosinMonitor Closely (1)paroxetine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tapentadolMonitor Closely (1)paroxetine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.tazemetostatMonitor Closely (1)paroxetine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tedizolidSerious - Use Alternative (1)tedizolid, paroxetine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.telavancinMonitor Closely (1)paroxetine and telavancin both increase QTc interval. Use Caution/Monitor.terbinafineMonitor Closely (1)terbinafine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.tetrabenazineMonitor Closely (1)paroxetine increases effects of tetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decrease tetrabenazine dose by 50% when coadministered with strong CYP2D6 inhibitors.Serious - Use Alternative (1)tetrabenazine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.thioridazineContraindicated (1)paroxetine increases levels of thioridazine by decreasing metabolism. Contraindicated. Risk of long QT syndrome.Serious - Use Alternative (3)paroxetine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. thioridazine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. thioridazine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.thiothixeneMonitor Closely (1)paroxetine, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).timololSerious - Use Alternative (1)paroxetine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.tinidazoleMonitor Closely (1)paroxetine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirSerious - Use Alternative (1)tipranavir will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.tolfenamic acidMonitor Closely (1)paroxetine, tolfenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.tolmetinMonitor Closely (1)paroxetine, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.tolterodineSerious - Use Alternative (1)paroxetine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.torsemideMinor (1)torsemide, paroxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.tramadolMonitor Closely (2)paroxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. paroxetine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.Minor (1)paroxetine decreases effects of tramadol by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of tramadol to active metabolite.tranylcypromineContraindicated (1)tranylcypromine and paroxetine both increase serotonin levels. Contraindicated.trazodoneMonitor Closely (1)trazodone and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)paroxetine and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.trifluoperazineMonitor Closely (3)paroxetine, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). trifluoperazine and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely. paroxetine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.trimethoprimMonitor Closely (1)paroxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.trimipramineMonitor Closely (1)trimipramine and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)paroxetine and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.tropisetronMonitor Closely (2)paroxetine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. paroxetine and tropisetron both increase QTc interval. Use Caution/Monitor.valbenazineMonitor Closely (2)valbenazine and paroxetine both increase QTc interval. Use Caution/Monitor. paroxetine will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Consider reducing valbenazine dose based on tolerability if coadministered with a strong CYP2D6 inhibitor.valerianMonitor Closely (1)valerian and paroxetine both increase sedation. Use Caution/Monitor.venlafaxineMonitor Closely (1)paroxetine and venlafaxine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)paroxetine and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)venlafaxine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.vilazodoneSerious - Use Alternative (1)paroxetine, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .vorapaxarMonitor Closely (1)paroxetine, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur; SSRIs and SNRIs may cause platelet serotonin depletion .voriconazoleMonitor Closely (1)paroxetine and voriconazole both increase QTc interval. Use Caution/Monitor.vortioxetineSerious - Use Alternative (1)paroxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)paroxetine, warfarin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serotonin release by platelets plays an important role in hemostasis. SSRIs and SNRIs may increase anticoagulation effect of warfarin. .zanubrutinibMonitor Closely (1)paroxetine, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.ziprasidoneMonitor Closely (2)paroxetine, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). paroxetine and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.zolmitriptanMonitor Closely (1)zolmitriptan and paroxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)paroxetine, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain. >10% (Based on 40 mg Dose) Nausea (15-24%) Insomnia (11-24%) Dry mouth (9-18%) Headache (17%) Asthenia (10-15%) Constipation (10-15%) Diarrhea (9-12%) Dizziness (6-14%) Ejaculation disorder (10-15%) Tremor (4-11%) 1-10% (Based on 40 mg Dose) Anxiety (5-10%) Blurred vision (5-10%) Decreased appetite (5-10%) Impotence (2-9%) Nervousness (2-5%) Paresthesia (2-5%) Hypomania (0.3 to 2.2%) Frequency Not Defined (Based on 40 mg Dose) Hypertension Tachycardia Emotional lability Pruritus Weight gain Arthralgia Tinnitus Vertigo Angle clossure glaucoma Serious Depression exacerbation Mania (rare) Serotonin syndrome Suicidal thoughts (rare) Suicide (rare) Seizure (rare) Toxic epidermal necrolysis Hyponatremia (rare) Bleeding, abnormal (rare) Acute hepatitis (rare) Stevens-Johnson Syndrome Bone fracture Akathisia Black Box Warnings In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years In children and young adults, risks must be weighed against the benefits of taking antidepressants Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy and dosage adjustments The patient’s family should communicate any abrupt changes in behavior to the healthcare provider Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy This drug is not approved for use in pediatric patientsContraindications Hypersensitivity Concomitant administration with pimozide or thioridazine Coadministration with serotonergic drugs Concomitant use or within 14 days of MAOIs increases risk of serotonin syndrome Reactions to concomitant administration with MAOIs include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma Starting paroxetine in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome If linezolid or IV methylene blue must be administered, discontinue SSRI immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring (5 weeks for fluoxetine), whichever comes first Cautions Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (18-24 years) Use caution in patients with history of seizure or suicidal thought/behavior; discontinue therapy in patients who develop seizures In patients with bipolar disorder, treating a depressive episode may precipitate a mixed/manic episode; prior to initiating treatment, screen patients for any personal or family history of bipolar disorder, mania, or hypomania Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include, nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures; a gradual reduction in dosage rather than abrupt cessation is recommended whenever possible Life-threatening serotonin syndrome reported with SNRIs and SSRIs alone; also with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy; avoid use in patients with untreated anatomically narrow angles Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (see Pregnancy) Risk of complications such as feeding difficulties, irritability, and respiratory problems reported in neonates exposed to SNRIs/SSRIs late in third trimester Risk of cardiovascular defects in infants whose mothers took drug during early pregnancy Withdraw gradually Use lower starting dose in renal impairment (CrCl <30 mL/min) or severe hepatic impairment In patients with symptomatic hyponatremia, discontinue therapy and institute appropriate medical intervention; elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs Inability to remain still due to feelings of agitation or restlessness reported; may occur within first few weeks of therapy May impair platelet aggregation especially when used in combination with aspirin or NSAIDs; increases risk of bleeding in patients taking anticoagulants/antiplatelets concomitantly Epidemiologic studies on bone fracture risk following exposure to some antidepressants, including SSRIs, have reported an association between antidepressant treatment and fractures; there are multiple possible causes for this observation and it is unknown to what extent fracture risk