Brand name: Paxil; Paxil CR; Brisdelle
Drug class: Selective Serotonin-reuptake Inhibitors

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).^{1 312 612}

Uses for PARoxetine

Major Depressive Disorder

Management of major depressive disorder in adults (paroxetine hydrochloride only).^{1 9 10 11 12 13 14 15 16 17 20 26 74 76 112 113 114 115 116 117 118 119 121 122 130 131 133 134 135 312 410 411 412}

Guidelines from the American Psychiatric Association (APA) and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another.^{613 614} Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, an SSRI, an SNRI, trazodone, vilazodone, or vortioxetine.⁶¹⁴ Select an initial antidepressant for treatment based on the following factors: patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; specific properties of the medication; and cost.⁶¹³

Obsessive-Compulsive Disorder (OCD)

Immediate-release formulations of paroxetine hydrochloride used for management of OCD in adults;^{1 617} has also been used in pediatric patients ≥7 years of age^{† [off-label]} .⁴²²

Legacy practice guidelines from APA list cognitive behavioral therapy and pharmacotherapy as safe and effective first-line treatments; for pharmacotherapy, SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) are first-line.⁶¹⁹ All SSRIs are equally effective, but individual patient response is variable; when selecting an SSRI, consider safety and acceptability of particular side effects for the patient, potential drug interactions, past treatment response, and the presence of comorbid medical conditions.⁶¹⁹ Updated guidelines from international experts list escitalopram, fluvoxamine, fluoxetine, paroxetine, and sertraline as first-line treatments for OCD in adults.⁶¹⁸

Panic Disorder

Management of panic disorder in adults (paroxetine hydrochloride only).^{1 48 53 54 184 187 190 192 312 413}

Legacy guidelines from APA state that SSRIs, SNRIs, TCAs, benzodiazepines, and cognitive behavioral therapy are effective.⁶²⁰ Evidence insufficient to recommend any intervention over others; base choice of initial therapy on patient preference, past treatment history, the presence of comorbid medical or psychiatric conditions, potential adverse effects, potential drug interactions, cost, and treatment availability.⁶²⁰ For patients who prefer to initiate pharmacological treatment, SSRIs and SNRIs are recommended first line.⁶²⁰ Updated guidelines from international experts state that first-line medications for panic disorder include citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, and venlafaxine.⁶²¹

Social Anxiety Disorder

Paroxetine hydrochloride used for management of social anxiety disorder in adults;^{1 312 414 415 416} has also been used in pediatric patients ≥8 years of age^{† [off-label]} .⁴²³

International experts state that escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine are recommended first-line agents for pharmacological treatment of social anxiety disorder in adults.⁶²¹

Generalized Anxiety Disorders

Management of generalized anxiety disorder in adults (immediate release formulations of paroxetine hydrochloride only).^{1 290 321 417 418 424}

International experts state that the SSRIs escitalopram, paroxetine, and sertraline, as well as the SNRIs venlafaxine and duloxetine, are first-line treatments for generalized anxiety disorder.⁶²¹

Posttraumatic Stress Disorder (PTSD)

Management of PTSD in adults (immediate-release formulations of paroxetine hydrochloride only).^{1 296 297}

Legacy guidelines from APA state that selection of a specific treatment strategy will depend on patient-specific factors (e.g., age, gender, history, comorbid medical and psychiatric conditions, propensity for aggression or self-harm).⁶²² SSRIs (i.e., fluoxetine, sertraline, paroxetine) are first-line treatments of choice for PTSD.⁶²²

The Department of Veterans Affairs and Department of Defense recommend specific types of psychotherapy (e.g., cognitive processing therapy, eye movement desensitization and reprocessing, prolonged exposure therapy) over pharmacologic interventions for PTSD.⁶²³ If pharmacologic therapy is used, paroxetine, sertraline, or venlafaxine is recommended.⁶²³

Premenstrual Dysphoric Disorder (PMDD)

Management of PMDD in adults (extended-release paroxetine hydrochloride only).^{312 419 420 421}

American College of Obstetricians and Gynecologists (ACOG) recommends SSRIs for management of affective premenstrual symptoms; SSRIs with evidence to support use in PMDD include sertraline, paroxetine, and fluoxetine.⁶²⁴ May administer SSRIs continuously or intermittently (i.e., during the luteal phase).⁶²⁴

Vasomotor Symptoms Due to Menopause

Treatment of moderate to severe vasomotor symptoms associated with menopause (paroxetine mesylate capsules only).^{425 612}

In general, systemic hormone therapy with estrogen alone or estrogen in combination with progestin is the most effective therapy for vasomotor symptoms related to menopause.^{625 626 627} For women who cannot or choose not to take systemic hormone therapy, effective nonhormonal alternatives include SSRIs (including paroxetine), SNRIs, gabapentin, and fezolinetant.^{625 626 627}

Premature Ejaculation

Has been used for the management of premature ejaculation^{† [off-label]}.^{169 170 171 172 173 280 281 628}

Bipolar Disorder

Has been used adjunctively for short-term management of acute depressive episodes in patients with bipolar disorder^{† [off-label]}; not recommended first line, reserve for use in patients with inadequate response to first-line agents.^{305 629}

PARoxetine Dosage and Administration

General

Pretreatment Screening

• Screen for a personal or family history of bipolar disorder, mania, or hypomania.^{1 312 612}

• Review current medications to evaluate for risk of serious drug interactions.^{1 312 612}

• Screen for recent monoamine oxidase inhibitor (MAOI) use; at least 14 days must elapse between discontinuation of an MAOI and initiation of paroxetine.^{1 312 612}

• Inquire about baseline sexual function.^{1 312 612}

• Obtain pregnancy status.^{1 312}

Patient Monitoring

• Monitor for any indication of clinical worsening of depression and emergence of suicidal thoughts and behaviors.^{1 312 612}

• Monitor for emergence of symptoms of serotonin syndrome such as mental status changes, autonomic instability, neuromuscular symptoms, seizures and/or GI symptoms.^{1 312 612}

• Monitor for changes in sexual function.^{1 312 612}

• Monitor for pregnancy in female patients.^{1 312}

• Monitor for bleeding events in patients taking concomitant aspirin, nonsteroidal anti-inflammatory agents (NSAIAs), antiplatelet drugs, warfarin, or other anticoagulants.^{1 312 612} Monitor INR in patients taking concomitant warfarin.^{1 312 612}

Dispensing and Administration Precautions

• The ISMP includes PARoxetine, DULoxetine, FLUoxetine, and piroxicam on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for these drugs.²⁷

• The 2023 American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults includes paroxetine on the list of PIMs that are best avoided by older adults in most circumstances or under specific situations, such as certain diseases, conditions, or care settings.⁹⁹⁹ The criteria are intended to apply to adults 65 years of age and older in all ambulatory, acute, and institutional settings of care, except hospice and end-of-life care settings.⁹⁹⁹ The Beers Criteria Expert Panel recommends that use of antidepressants with strong anticholinergic activity such as paroxetine be avoided in such patients.⁹⁹⁹

Other General Considerations

• Adverse reactions may occur upon discontinuation.^{1 312} Do not discontinue abruptly.^{1 312} Gradually reduce the dosage when discontinuing treatment.^{1 312}

• Once paroxetine is discontinued, at least 14 days must elapse before initiating an MAOI.^{1 312 612}

Administration

Oral Administration

Paroxetine is commercially available in the US as paroxetine hydrochloride conventional film-coated tablets, extended-release tablets, and oral suspension and as paroxetine mesylate conventional capsules.^{1 312 612} Conventional tablets of paroxetine hydrochloride and paroxetine mesylate capsules are not bioequivalent.³⁶⁶

Administer paroxetine hydrochloride conventional tablets, extended-release tablets, and oral suspension once daily (in the morning) without regard to meals.^{1 312} Administer paroxetine mesylate capsules once at bedtime with or without food.⁶¹²

Shake paroxetine hydrochloride oral suspension well just prior to administration.¹

Swallow extended-release tablets whole; do not chew or crush.³¹²

Dosage

Available as paroxetine hydrochloride and paroxetine mesylate; dosage expressed in terms of paroxetine.^{1 312 612}

When discontinuing paroxetine hydrochloride, gradually reduce dosage rather than stopping abruptly whenever possible.^{1 312} Adverse reactions may occur upon discontinuation of paroxetine.^{1 312}

Adults

Major Depressive Disorder

Oral

Paroxetine hydrochloride conventional tablets or suspension: Initially, 20 mg once daily.¹ If no improvement, dosage may be increased in 10-mg increments at weekly intervals to a maximum of 50 mg daily.¹

Paroxetine hydrochloride extended-release tablets: Initially, 25 mg once daily.³¹² If no improvement, dosage may be increased in 12.5-mg increments at weekly intervals to a maximum of 62.5 mg daily.³¹²

Obsessive-Compulsive Disorder

Oral

Paroxetine hydrochloride conventional tablets or suspension: Initially, 20 mg once daily.¹ If no improvement, dosage may be increased in 10-mg increments at weekly intervals to a maximum of 60 mg daily.¹

Panic Disorder

Oral

Paroxetine hydrochloride conventional tablets or suspension: Initially, 10 mg once daily.¹ If no improvement, dosage may be increased in 10-mg increments at weekly intervals, to a maximum of 60 mg daily.¹

Paroxetine hydrochloride extended-release tablets: Initially, 12.5 mg once daily.³¹² If no improvement, dosage may be increased in 12.5-mg increments at weekly intervals to a maximum of 75 mg daily.³¹²

Social Anxiety Disorder

Oral

Paroxetine hydrochloride conventional tablets or suspension: 20 mg once daily; doses up to 60 mg daily have been studied but no additional clinical benefit was observed above 20 mg daily.¹

Paroxetine hydrochloride extended-release tablets: Initially, 12.5 mg once daily.³¹² If dosage is increased, use 12.5-mg increments at weekly intervals to a maximum of 37.5 mg daily.³¹²

Generalized Anxiety Disorders

Oral

Paroxetine hydrochloride conventional tablets or suspension: Initially, 20 mg daily; no additional clinical benefit was observed with higher dosages (above 20 mg daily).¹

Posttraumatic Stress Disorder

Oral

Paroxetine hydrochloride conventional tablets or suspension: Initially, 20 mg daily; if no improvement, dosage may be increased in 10-mg increments at weekly intervals, to a maximum of 50 mg daily.¹

Premenstrual Dysphoric Disorder

Oral

Paroxetine hydrochloride extended-release tablets: Initially, 12.5 mg once daily; may be administered daily throughout menstrual cycle or intermittently only during luteal phase (i.e., starting daily dosage 14 days prior to anticipated onset of menstruation and continuing through onset of menses).³¹² Intermittent dosing is repeated with each new cycle.³¹² If no improvement, dosage may be increased at weekly intervals to a maximum of 25 mg daily, depending on tolerability.³¹²

Vasomotor Symptoms Due to Menopause

Oral

Paroxetine mesylate capsules: 7.5 mg once daily at bedtime.⁶¹²

Special Populations

Hepatic Impairment

Paroxetine hydrochloride conventional tablets or suspension: In patients with severe hepatic impairment, 10 mg daily initially.¹ Do not exceed 40 mg daily.¹

Paroxetine hydrochloride extended-release tablets: In patients with severe hepatic impairment, 12.5 mg daily initially.³¹² If necessary, reduce initial dose and increase intervals between upward titration of the dosage.³¹² Do not exceed 50 mg daily for major depressive disorder or panic disorder treatment.³¹² Do not exceed 37.5 mg daily for social anxiety disorder treatment.³¹²

Paroxetine mesylate capsules: No dosage adjustment necessary.⁶¹²

Renal Impairment

Paroxetine hydrochloride conventional tablets or suspension: In patients with severe renal impairment, 10 mg daily initially.¹ Do not exceed 40 mg daily.¹

Paroxetine hydrochloride extended-release tablets: In patients with severe renal impairment, 12.5 mg daily initially.³¹² If necessary, reduce initial dose and increase intervals between upward titration of the dosage.³¹² Do not exceed 50 mg daily for major depressive disorder or panic disorder treatment.³¹² Do not exceed 37.5 mg daily for social anxiety disorder treatment.³¹²

Paroxetine mesylate capsules: No dosage adjustment necessary.⁶¹²

Geriatric Patients

Paroxetine hydrochloride conventional tablets or suspension: For elderly patients, 10 mg daily initially.¹ Do not exceed 40 mg daily.¹

Paroxetine hydrochloride extended-release tablets: In elderly patients, 12.5 mg daily initially.³¹² Do not exceed 50 mg daily for major depressive disorder or panic disorder treatment.³¹² Do not exceed 37.5 mg daily for social anxiety disorder treatment.³¹²

Paroxetine mesylate capsules: No dosage adjustment necessary.⁶¹²

Pharmacogenomic Considerations

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provide dosing recommendations for paroxetine based on CYP2D6 phenotype.⁷⁰⁰ For patients identified as CYP2D6 ultrarapid metabolizers, select an alternative drug not predominantly metabolized by CYP2D6.⁷⁰⁰ For CYP2D6 intermediate metabolizers, consider a lower starting dose and a slower titration schedule compared to the recommended starting dose.⁷⁰⁰ For CYP2D6 poor metabolizers, consider a 50% reduction of the recommended starting dose, a slower titration schedule, and a 50% lower maintenance dose as compared with normal metabolizers.⁷⁰⁰

Cautions for PARoxetine

Contraindications

• Concomitant use of MAOIs (including linezolid and IV methylene blue) or use within 14 days of discontinuing an MAOI, due to an increased risk of serotonin syndrome.^{1 312 612}

• Concomitant use of thioridazine, due to the risk of QT prolongation.^{1 312 612}

• Concomitant use of pimozide, due to the risk of QT prolongation.^{1 312 612}

• Known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any of the inactive ingredients of the formulation.^{1 312 612}

• Paroxetine mesylate only: Pregnancy; vasomotor symptoms do not occur during pregnancy and paroxetine can cause fetal harm.⁶¹²

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients.^{1 312 612} (See Boxed Warning.) Monitor all antidepressant-treated patients for any indication of clinical worsening and emergence of suicidal thoughts and behaviors, especially during initial few months of therapy, and at times of dosage changes.^{1 312 612} Counsel family members or caregivers to monitor for changes and to alert the clinician.^{1 312 612} Consider changing the therapeutic regimen, including discontinuation of paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.^{1 312 612}

Other Warnings and Precautions

Serotonin Syndrome

Can precipitate serotonin syndrome, a potentially life-threatening condition.^{1 312 612} Risk increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines and St. John’s Wort) and with drugs that impair metabolism of serotonin (i.e., MAOIs).^{1 312 612} Serotonin syndrome can also occur when these drugs are used alone.^{1 312 612}

Symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).^{1 312 612}

Concomitant use of paroxetine with MAOIs is contraindicated.^{1 312 612} Do not initiate paroxetine in a patient being treated with MAOIs such as linezolid or IV methylene blue.^{1 312 612} If necessary to initiate treatment with an MAOI such as linezolid or IV methylene blue, discontinue paroxetine before initiating MAOI.^{1 312 612}

Monitor all patients for emergence of serotonin syndrome.^{1 312 612} Discontinue treatment with paroxetine and any concomitant serotonergic agents immediately if symptoms occur, and initiate supportive symptomatic treatment.^{1 312 612} If concomitant use with other serotonergic drugs clinically warranted, inform patients of increased risk for serotonin syndrome and monitor for symptoms.^{1 312 612}

Drug Interactions Leading to QT Prolongation

CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide.^{1 312 612} Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, use of paroxetine is contraindicated in combination with thioridazine or pimozide.^{1 312 612}

Fetal/Neonatal Morbidity and Mortality

Exposure to paroxetine in first trimester of pregnancy is associated with a less than 2-fold increase in the rate of cardiovascular malformations among infants.^{1 312 612}

For women who intend to become pregnant or who are in their first trimester of pregnancy, initiate paroxetine only after consideration of other available treatment options.^{1 312 612}

Increased Risk of Bleeding

Increased risk of bleeding events including ecchymoses, hematomas, epistaxis, petechiae, GI bleeding, postpartum hemorrhage, and life-threatening bleeding.^{1 312 612} Concomitant use of aspirin, NSAIAs, other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk.^{1 312 612}

Inform patients about increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents or anticoagulants.^{1 312 612} For patients taking warfarin, carefully monitor INR.^{1 312 612}

Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with paroxetine or another antidepressant may precipitate a mixed/manic episode.^{1 312 612}

Prior to initiating treatment, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.^{1 312 612}

Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. ^{1 312}

Reduce paroxetine dosage gradually rather than discontinuing abruptly.^{1 312}

Seizures

Patients with a history of seizures were excluded from clinical studies of paroxetine.^{1 312}

Use with caution in patients with a seizure disorder; discontinue drug in any patient who develops seizures.^{1 312 612}

Angle-Closure Glaucoma

Cases of angle-closure glaucoma reported.^{1 312 612}

Avoid use in patients with untreated anatomically narrow angles.^{1 312 612}

Hyponatremia

Hyponatremia, most likely due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), may occur.^{1 312 612} Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls.^{1 312 612} Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.^{1 312 612} Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk.^{1 312 612}

In patients with symptomatic hyponatremia, discontinue paroxetine and institute appropriate medical intervention.^{1 312 612}

Reduction of Efficacy of Tamoxifen

Efficacy of tamoxifen may be reduced with concomitant use of paroxetine.^{1 312 612}

When tamoxifen is used for prevention or treatment of breast cancer, consider using an antidepressant with little to no CYP2D6 inhibition.^{1 312 612}

Bone Fracture

Association between antidepressant (including SSRI) treatment and bone fractures reported in epidemiological studies.^{1 312 612}

Sexual Dysfunction

May cause symptoms of sexual dysfunction.^{1 312 612} In male patients, may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction.^{1 312} In female patients, may result in decreased libido and delayed or absent orgasm.^{1 312 612}

Inquire about sexual function prior to initiation and inquire specifically about changes in sexual function during treatment.^{1 312 612} Obtain a detailed history (including timing of symptom onset) when evaluating changes in sexual function to rule out other causes, including the underlying psychiatric disorder.^{1 312 612} Discuss potential management strategies to support patients in making informed decisions about treatment.^{1 312 612}

Specific Populations

Pregnancy

Paroxetine mesylate capsules are contraindicated for use in pregnant women because menopausal vasomotor symptoms do not occur during pregnancy and paroxetine can cause fetal harm.⁶¹²

Advise patients to register in the National Pregnancy Registry for Antidepressants by calling 1-866- 961-2388 or visiting online at [Web].^{1 312}

Associated with a less than 2-fold increase in cardiovascular malformations when administered to pregnant women during the first trimester.^{1 312} Risk of persistent pulmonary hypertension of the newborn (PPHN) and/or poor neonatal adaptation with exposure during pregnancy.^{1 312} Use in the month before delivery may be associated with an increased risk of postpartum hemorrhage.^{1 312} There are also risks associated with untreated depression in pregnancy.^{1 312}

Consider risk of untreated depression when discontinuing or changing treatment with antidepressants during pregnancy and postpartum.^{1 312}

For women who intend to become pregnant or who are in their first trimester of pregnancy, initiate paroxetine only after consideration of the other available treatment options.^{1 312}

Lactation

Distributed into human milk.^{1 312 612} Monitor for adverse symptoms of agitation, irritability, poor feeding, and poor weight gain in exposed infants.^{1 312}

Consider developmental and health benefits of breast-feeding along with mother’s clinical need for paroxetine and any potential adverse effects on the breast-fed child from paroxetine or from the underlying maternal condition.^{1 312 612}

Pediatric Use

Safety and efficacy of paroxetine hydrochloride not established in children <18 years of age.^{1 312} Main safety concern is the increased risk of suicidal thoughts and behaviors.^{1 312}

Paroxetine mesylate capsules not indicated for use in pediatric population.⁶¹²

Geriatric Use

Pharmacokinetic studies revealed decreased clearance in the elderly; lower starting dose of paroxetine hydrochloride recommended.^{1 312} No overall differences in safety or effectiveness observed between elderly and younger patients.^{1 312}

Clinically significant hyponatremia may occur in elderly patients, who may be at greater risk for this adverse reaction.^{1 312 612}

Clinical studies of paroxetine mesylate capsules did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger subjects.⁶¹² Elderly patients may have elevated paroxetine plasma concentrations compared to younger patients.⁶¹² However, no dosage adjustment of paroxetine mesylate capsules necessary.⁶¹²

Hepatic Impairment

Increased plasma concentrations reported; reduce initial dosage of paroxetine hydrochloride if impairment is severe.^{1 312}

No dosage adjustment of paroxetine mesylate capsules required.⁶¹²

Renal Impairment

Increased plasma concentrations reported; reduce initial dosage of paroxetine hydrochloride if impairment is severe.^{1 312}

No dosage adjustment of paroxetine mesylate capsules required.⁶¹²

Common Adverse Effects

Most common adverse effects with paroxetine hydrochloride conventional tablets and suspension (≥5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn.¹

Most common adverse effects with paroxetine hydrochloride extended-release tablets (≥5% and at least twice placebo) are abnormal ejaculation, abnormal vision, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, insomnia, libido decreased, nausea, somnolence, sweating, tremor.³¹²

Most common adverse effects with paroxetine mesylate capsules (≥2% and at a higher incidence that placebo) are headache, fatigue, malaise, lethargy, nausea, vomiting.⁶¹²

Drug Interactions

Metabolized partially by CYP2D6.^{1 312 612} Strong inhibitor of the activity of CYP2D6 and to a lesser extent CYP3A4.^{1 312 612}

Drugs Undergoing Hepatic Metabolism or Affecting Hepatic Microsomal Enzymes

Drugs Metabolized by CYP2D6: Possible increased plasma concentrations of the CYP2D6 substrates.^{1 312 612} Examples of drugs that are CYPD2D6 substrates include propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, and risperidone.^{1 312 612} Reduce dosage of concomitantly administered CYP2D6 substrate.^{1 312 612} Increase in dosage of CYP2D6 substrate may be needed with paroxetine discontinuation.^{1 312 612}

Drugs Metabolized by CYP3A4: Extent of paroxetine’s inhibition of CYP3A4 activity unlikely to be of clinical importance based on in vivo and in vitro studies.^{1 312 612}

Serotonergic Drugs

Potentially life-threatening serotonin syndrome with other serotonergic drugs.^{1 312 612} Examples of serotonergic drugs include other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort.^{1 312 612}

Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases.^{1 312 612} If serotonin syndrome occurs, consider discontinuing paroxetine and/or any concurrently administered serotonergic agents.^{1 312 612}

Drugs Highly Bound to Plasma Protein

Potential displacement of or by other highly-protein bound drugs (e.g., warfarin).^{1 312 612} Paroxetine does not alter in vitro protein binding of phenytoin or warfarin.^{1 312 612}

Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted.^{1 312 612}

Drugs that Interfere with Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect hemostasis such as aspirin, clopidogrel, heparin, or warfarin.^{1 312 612}

Inform patients of increased risk of bleeding associated with concomitant use of paroxetine and antiplatelet and anticoagulant agents.^{1 312 612} For patients taking warfarin, closely monitor INR.^{1 312 612}

Monoamine Oxidase Inhibitors

Concomitant use of paroxetine with MAO inhibitors, including selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, and methylene blue, is contraindicated due to the risk of serotonin syndrome.^{1 312 612}

At least 14 days must elapse between discontinuation of an MAOI and initiation of paroxetine; additionally, at least 14 days must elapse after stopping paroxetine before starting an MAOI.^{1 312 612}

Specific Drugs

PARoxetine Pharmacokinetics

Absorption

Bioavailability

Completely absorbed following oral administration.^{1 312 612} ; absorption rate is reduced and slightly delayed with extended-release tablet.³¹²

Equally bioavailable from commercially available paroxetine hydrochloride conventional tablets and suspension.¹

Conventional tablets of paroxetine hydrochloride (Paxil) and paroxetine mesylate capsules are not bioequivalent.³⁶⁶

Food

Administration of single dose of paroxetine hydrochloride with food resulted in a 6 and 29% increase in AUC and peak plasma concentration, respectively; time to peak plasma concentrations decreased from 6.4 to 4.9 hours.¹

Distribution

Extent

Widely distributed in the body, including CNS and breast milk.¹

Plasma Protein Binding

Approximately 95 and 93% bound to plasma proteins at plasma concentrations of 100 and 400 ng/mL, respectively.¹

Elimination

Metabolism

Extensively metabolized, ^{1 312 612} partially by CYP2D6.¹ Metabolites are essentially inactive.^{1 6 84}

Inhibits activity of CYP2D6.^{1 312 612}

Elimination Route

Eliminated principally in urine and feces (probably via bile).^{1 94}

Half-life

21 hours (administered as paroxetine hydrochloride immediate-release formulation); between 15—20 hours (administered as paroxetine hydrochloride extended-release formulation).^{1 312}

Special Populations

In patients with renal impairment (Cl_cr <30 mL/minute), mean plasma paroxetine concentrations are approximately 4 times greater than those seen in healthy individuals.⁶¹²

Hepatic impairment may increase plasma concentrations twofold.⁶¹²

Stability

Storage

Oral

Paroxetine Hydrocholoride Conventional Tablets

15–30°C.¹

Paroxetine Hydrochloride Extended-release Tablets

≤25°C; excursion permitted from 15–30°C..³¹²

Paroxetine Hydrochloride Suspension

≤25°C.¹

Paroxetine Mesylate Conventional Capsules

≤25°C.⁶¹² Protect capsules from light and humidity.⁶¹²

Actions

• Potent and highly selective reuptake inhibitor of serotonin.^{1 312 612}

• Mechanism of action as an antidepressant presumed to be linked to potentiation of serotonergic activity in the CNS resulting from inhibition of CNS neuronal reuptake of serotonin (5-HT).^{1 4 6 84}

• Precise mechanism of action in obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder not fully elucidated but appears to involve inhibition of serotonin reuptake.^{1 19 55 312}

• Has little or no effect on other neurotransmitters or any clinically important anticholinergic, antihistaminic, or adrenergic (α₁, α₂, β) blocking activity at usual therapeutic dosages.^{1 4 84 85 312 612}

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).^{1 312 612}

• Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down and instruct them to report such symptoms to their clinician.^{1 312 612}

• Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine with other serotonergic drugs, including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, monoamine oxidase inhibitors, both those intended to treat psychiatric disorders and others, such as linezolid).^{1 312 612} Instruct patients to contact their clinician or report to the emergency room if they experience signs or symptoms of serotonin syndrome.^{1 312 612}

• Advise patients to inform their clinician if they are taking, or plan to take, any prescription or OTC drugs, since there is a potential for drug-drug interactions.^{1 312 612}

• Inform patients about the possible increased risk of bleeding associated with concomitant use of paroxetine and aspirin, nonsteroidal anti-inflammatory agents, other antiplatelet drugs, warfarin, or other anticoagulants.^{1 312 612} Advise patients to inform their clinician if they are taking or planning to take any prescription or OTC medications that increase the risk of bleeding.^{1 312 612}

• Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the clinician.^{1 312 612}

• Advise patients not to abruptly discontinue paroxetine and to discuss any tapering regimen with their clinician.^{1 312} Inform patients that adverse reactions can occur when paroxetine is discontinued.^{1 312}

• Advise patients that use of paroxetine may cause symptoms of sexual dysfunction in both male and female patients.^{1 312 612} Inform patients that they should discuss any changes in sexual function and potential management strategies with their clinician.^{1 312 612}

• Instruct patients to shake the oral suspension well before administration.¹

• Advise patients to notify their clinician if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing.^{1 312 612}

• Advise women to notify their clinician if they become pregnant or intend to become pregnant during treatment with paroxetine.^{1 312 612} Advise women of risks associated with first trimester use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN).^{1 312 612}

• Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to paroxetine during pregnancy.^{1 312}

• Advise breast-feeding women using paroxetine to monitor infants for agitation, irritability, poor feeding, and poor weight gain and to seek medical care if they notice these signs.^{1 312}

• Advise men that paroxetine may affect sperm quality, which may impair fertility; it is not known if this effect is reversible.^{1 312}

• Advise patients that taking paroxetine capsules can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma.^{1 312 612} Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.^{1 312 612}

• Advise patients about the risk of hyponatremia, particularly elderly patients and those who are taking diuretics or are volume-depleted.^{1 312 612}

• Inform patients that there is the possibility for an increased risk of fracture.^{1 312 612}

• Inform patients of other important precautionary information.^{1 312 612}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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