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Generic Name: Paroxetine Hydrochloride
Class: Selective Serotonin-reuptake Inhibitors
VA Class: CN609
Chemical Name: trans-(-)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine hydrochloride hemihydrate
Molecular Formula: C19H20FNO3•HCl•½H2O
CAS Number: 110429-35-1

Warning(s)

  • Suicidality
  • Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.314 315 611 Paroxetine is not approved for use in pediatric patients.611 (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and was reduced in adults ≥65 years of age with antidepressants compared with placebo.314 315 611

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.314 315 320 611

  • Appropriately monitor and closely observe all patients who are started on paroxetine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.314 315 320 611 (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).1 2 5 6

Uses for Paxil

Major Depressive Disorder

Management of major depressive disorder.1 5 8 9 10 11 12 13 14 15 16 17 18 19 20 21 26 30 39 42 74 76 131 132 134 135 155

Efficacy in hospital settings not established.1

Obsessive-Compulsive Disorder (OCD)

Management of OCD;1 49 50 SSRIs reduce but do not completely eliminate obsessions and compulsions.1

Panic Disorder

Management of panic disorder with or without agoraphobia.1 48 53 54 180 186 187 190 192 272

Social Phobia

Management of social phobia (social anxiety disorder).1 155 158 159 160 161

Anxiety Disorders

Management of generalized anxiety disorder.1

Posttraumatic Stress Disorder (PTSD)

Management of PTSD (alone or in combination with psychotherapy).1 168 296 297 298

Premenstrual Dysphoric Disorder (PMDD)

Management of PMDD.79 80 155 162

Premature Ejaculation

Has been used for the management of premature ejaculation.169 170 171 172 173 174

Diabetic Neuropathy

Has been used for the management of diabetic neuropathy.24 136

Chronic Headache

Has been used for the management of chronic headache.155 163 164

Paxil Dosage and Administration

General

  • Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor intended to treat psychiatric disorders and initiation of paroxetine, and vice versa.611 (See Contraindications and Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.314 315 320 611 (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Sustained therapy may be required;1 42 51 52 101 102 103 104 129 130 133 periodically reassess for need for continued therapy.1

  • Avoid abrupt discontinuance of therapy;24 184 197 198 200 204 to avoid withdrawal reactions, taper dosage gradually over a period of several weeks.184 194 197 198 200 (See Withdrawal of Therapy under Cautions.)

Administration

Oral Administration

Administer orally once daily (in the morning) without regard to meals;1 7 8 19 92 312 however, administration with food may minimize adverse GI effects.8 19

Shake oral suspension well just prior to administration.1

Swallow extended-release tablets whole; do not chew or crush.304

Dosage

Available as paroxetine hydrochloride; dosage expressed in terms of paroxetine.1

Adults

Major Depressive Disorder
Oral

Conventional tablets or suspension: Initially, 20 mg once daily.1 304 If no improvement, dosage may be increased in 10-mg increments at weekly intervals.1 304

Extended-release tablets: Initially, 25 mg once daily.1 304 If no improvement, dosage may be increased in 12.5-mg increments at weekly intervals.1 304

Optimum duration not established; may require several months of therapy or longer.1 22 42 101 102 103 104 129 130 133 304 Antidepressant efficacy demonstrated for up to 1 year at mean dosage of 30 mg daily as conventional tablets or suspension, which corresponds to a 37.5 mg daily dosage as extended-release tablets.1 133

Obsessive-Compulsive Disorder
Oral

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 40 mg daily.1

Optimum duration not established; efficacy has been demonstrated in a 6-month relapse prevention trial.1 Obsessive-compulsive disorder is chronic and requires several months or longer of sustained therapy.1 51 52 May continue therapy in responding patients,1 51 52 but use lowest effective dosage and periodically reassess need for continued therapy.1

Panic Disorder
Oral

Conventional tablets or suspension: Initially, 10 mg once daily.1 48 If no improvement, dosage may be increased in 10-mg increments at weekly intervals, to 40 mg daily.1 48

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.312

Optimum duration not established; efficacy demonstrated in a 3-month relapse prevention trial.1 48 54 184 May continue therapy in responding patients,1 48 54 184 but use lowest effective dosage and periodically reassess need for continued therapy.1

Social Phobia
Oral

Conventional tablets or suspension: 20 mg once daily; no additional clinical benefit was observed with higher dosages.1

Extended-release tablets: Initially, 12.5 mg once daily.312 If dosage is increased, use 12.5-mg increments at weekly intervals.312

Long-term efficacy (>12 weeks) not demonstrated; may consider continuation in patient who responds, but use lowest effective dosage and periodically reassess need for continued therapy.1

Anxiety Disorders
Oral

Conventional tablets or suspension: Initially, 20 mg daily; no additional clinical benefit was observed with higher dosages.1 If needed, dosage may be increased in 10-mg increments at weekly intervals.1

Optimum duration not established; efficacy has been demonstrated in a 24-week relapse prevention trial.1 321 Generalized anxiety disorder is chronic.1 321 May continue therapy in responding patients.1 321 If used for extended periods, adjust dosage so that patients are maintained on lowest effective dosage and periodically reassess need for continued therapy.1

Posttraumatic Stress Disorder
Oral

Conventional tablets or suspension: 20 mg daily; insufficient evidence to suggest greater clinical benefit with higher dosages.1 If needed, dosage may be increased in 10-mg increments at weekly intervals.1

Consider alternative therapy if patient fails to achieve ≥25% reduction in PTSD symptoms at week 8.300 If >75% reduction in PTSD symptoms and response maintained for ≥3 months, may consider up to 24 months of drug therapy.300 If used for extended periods, adjust dosage so that patients are maintained on lowest effective dosage and periodically reassess need for continued therapy.1

Premenstrual Dysphoric Disorder
Oral

Conventional tablets or suspension: 5–30 mg daily.79

Extended-release tablets: Initially, 12.5 mg once daily; may be administered daily throughout menstrual cycle or only during luteal phase.312 Dosage may be increased in intervals of ≥1 week.312 Dosages of 12.5–25 mg were effective in clinical studies.312

Premature Ejaculation
Oral

Conventional tablets or suspension: 10–40 mg once daily.172 173 279 280 281 Alternatively, 20 mg taken 3–4 hours before planned intercourse on an “as needed” basis.280 281

Diabetic Neuropathy
Oral

Conventional tablets or suspension: 40 mg daily.24 136

Chronic Headache
Oral

Conventional tablets or suspension: 10–50 mg daily for 3–9 months.164

Prescribing Limits

Adults

Major Depressive Disorder
Oral

Conventional tablets or suspension: Maximum 50 mg daily.

Extended-release tablets: 62.5 mg daily.1 304

Obsessive-Compulsive Disorder
Oral

Conventional tablets or suspension: Maximum 60 mg daily.1

Panic Disorder
Oral

Conventional tablets or suspension: Maximum 60 mg daily.1

Extended-release tablets: 75 mg daily.312

Social Phobia
Oral

Extended-release tablets: 37.5 mg daily.312

Special Populations

Hepatic Impairment

Oral

In patients with severe hepatic impairment, an initial dosage of 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets).1 304 If no clinical improvement is apparent, dosage may be titrated with caution up to a maximum of 40 mg daily (for conventional tablets or suspension) or 50 mg (for extended-release tablets).1 98 99 304

Renal Impairment

Oral

In patients with severe renal impairment, an initial dosage of 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets).1 304 If no clinical improvement is apparent, dosage may be titrated with caution up to a maximum of 40 mg daily (for conventional tablets or suspension) or 50 mg (for extended-release tablets).1 98 99 304

Geriatric or Debilitated Patients

Initially, 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets); if no clinical improvement is apparent, dosage may be titrated up to a maximum of 40 mg daily (as conventional tablets or suspension) or 50 mg daily (as extended-release tablets).1 95 304

Cautions for Paxil

Contraindications

  • Paroxetine is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with an MAO inhibitor intended to treat psychiatric disorders.611 Conversely, MAO inhibitors intended to treat psychiatric disorders are contraindicated within 2 weeks of paroxetine discontinuance.611 (See Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)

  • Initiation of paroxetine is contraindicated in patients receiving MAO inhibitors such as linezolid or IV methylene blue.611 (See Specific Drugs under Interactions.)

  • Concurrent therapy with thioridazine.1 (See Drug Interaction with Thioridazine under Warnings.)

  • Concurrent pimozide therapy.1 312 (See Interactions.)

  • Known hypersensitivity to paroxetine or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.314 315 320 611 However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.314 315 320 611

Appropriately monitor and closely observe patients receiving paroxetine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.314 315 320 611 (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.314 320 611 Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.314 315 320 611 If decision is made to discontinue therapy, taper paroxetine dosage as rapidly as is feasible but consider risks of abrupt discontinuance.314 611 (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.314 611

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.314 611

Bipolar Disorder

May unmask bipolar disorder.1 312 314 (See Activation of Mania or Hypomania under Cautions.) Paroxetine is not approved for use in treating bipolar depression.1 312

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.1 312 314

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported with SSRIs and SNRIs alone, but particularly during concurrent therapy with other serotonergic drugs (e.g., 5-HT1 receptor agonists [“triptans”], TCAs, amphetamines, buspirone, fentanyl, lithium, tramadol, tryptophan, St. John's wort [Hypericum perforatum]) and with drugs that impair the metabolism of serotonin (particularly MAO inhibitors, both those used to treat psychiatric disorders and others, such as linezolid and methylene blue).611 (See Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).611

Paroxetine is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with MAO inhibitors intended to treat psychiatric disorders.611 Do not initiate paroxetine in patients treated with other MAO inhibitors such as linezolid or IV methylene blue.611 (See Specific Drugs under Interactions.)

If concurrent therapy with other serotonergic drugs is clinically warranted, advise patient of potentially increased risk for serotonin syndrome, particularly during initiation of therapy and dosage increases.611

Monitor patients receiving paroxetine for the development of serotonin syndrome.611 If manifestations occur, immediately discontinue paroxetine and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.611

Drug Interaction with Thioridazine

May inhibit CYP2D6, resulting in increased risk of QT-interval prolongation and/or ventricular tachycardia of the torsades de pointes type associated with elevated plasma concentrations of thioridazine.1 (See Contraindications.)

Fetal/Neonatal Morbidity and Mortality

May increase risk of fetal defects (e.g., cardiovascular malformations, principally ventricular and atrial septal defects; other major congenital malformations) when administered to pregnant women.326 333 337 338 358 a c

If a patient becomes pregnant during treatment, advise patient of the potential hazard to the fetus.337 338 a c Unless the potential benefits to the mother justify continuing treatment, consider discontinuing paroxetine therapy or switching to another antidepressant.337 338 a c (See General under Dosage and Administration.) For women who intend to become pregnant or are in their first trimester of pregnancy, initiate paroxetine only after consideration of other available treatment options.337 338 a c

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in neonates exposed to paroxetine, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery.1 312 327 328 329 330 331 332

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.370 600 601 602 603 604 605 606 610 611

Carefully consider both the potential risks and benefits of treatment when used during the third trimester of pregnancy.1 312 326 328 329 330 Be aware that in a longitudinal study involving women with a history of major depressive disorder who were euthymic while receiving antidepressant therapy at the beginning of pregnancy, women who discontinued antidepressant therapy during pregnancy were more likely to experience a relapse of depression than those who remained on antidepressant therapy.1 312

Consult joint APA and ACOG guidelines (at ) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.600 608

General Precautions

Activation of Mania or Hypomania

Possible activation of mania or hypomania.1 2 Use with caution in patients with a history of mania.1 312 (See Bipolar Disorder under Cautions.)

Seizures

Seizures have been reported.1 2 Limited experience with use of paroxetine in patients with a history of seizures; use with caution in such patients.1 Discontinue if seizures occur.1

Akathisia

Akathisia has been reported.1 226 227 312 Most likely to occur within the first few weeks of therapy.1 312

Hyponatremia

May occur secondary to SIADH;24 25 28 apparently reversible following discontinuance of the drug and/or fluid restriction.1 22 24 28 210 215 217 Occurs mainly in older patients1 22 24 25 28 and those receiving diuretics or otherwise volume depleted.1 (See Geriatric Use under Cautions.)

Abnormal Bleeding

Possible increased risk of bleeding, including upper GI bleeding;1 312 323 324 325 use with caution.a

Concomitant use of an NSAIA (e.g., aspirin) or warfarin may potentiate such risk.1 6 147 312 323 324 325

Concomitant Disease

May be less cardiotoxic than most older antidepressant agents but experience is limited in patients with recent MI or unstable heart disease.1 2 18 24 145 Use with caution.1 98 99 145 225

May cause mydriasis.1 299 Use with caution in patients with angle-closure glaucoma.1

Cognitive and Motor Performance

Does not appear to produce substantial cognitive or motor impairment,1 2 3 18 19 24 62 72 73 but patients should be cautioned to avoid activities requiring alertness or physical coordination until effects on individual are known.1 62

Withdrawal of Therapy

Possible withdrawal reactions following abrupt discontinuance or intermittent noncompliance with therapy.1 23 24 32 33 46 47 196 197 198 199 200 201 202 203 204 205 206 Avoid abrupt discontinuance of therapy;24 184 197 198 200 204 taper dosage gradually over a period of several weeks.184 194 197 198 200

If intolerable symptoms occur, reinstitute at the previously prescribed dosage until such symptoms abate.1 304 Clinicians may resume dosage reductions at that time but at a more gradual rate.1 304

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT have not been systematically evaluated.1

Specific Populations

Pregnancy

See Fetal/Neonatal Morbidity and Mortality under Cautions.

Effect of paroxetine on labor and delivery unknown.1 343 However, there have been postmarketing reports of premature births in pregnant women who have received paroxetine or other SSRIs.1 312 343

Lactation

Distributed into human milk;1 100 use with caution.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 271 312

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).314 315 316 However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.368 No suicides occurred in these pediatric trials.314 315 368 611

Carefully consider these findings when assessing potential benefits and risks of paroxetine in a child or adolescent for any clinical use.314 315 320 368 611 (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Possible decreased clearance; however, efficacy and adverse effects similar to those in younger adults.1 2 4 7 18 24 83 95 96 97 Initiate therapy at a lower dosage.1 8 95 (See Geriatric or Debilitated Patients under Dosage and Administration.)

May be more likely than younger patients to develop hyponatremia and transient SIADH.1 22 24 25 28 214 215 Periodically monitor serum sodium concentrations, especially during the first several months of therapy.181 217

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.314 315 611 (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Increased plasma concentrations1 4 98 99 and decreased clearance reported.1 137 Use with caution; use at a reduced initial dosage if impairment is severe.1 98 99 145 225 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Increased plasma concentrations1 4 98 99 and decreased clearance reported.1 137 Use with caution; use at a reduced initial dosage if impairment is severe.1 98 99 145 225 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nervous system effects (e.g., asthenia, somnolence, dizziness, insomnia, tremor, nervousness), GI effects (e.g., nausea, decreased appetite, constipation, dry mouth), impotence, ejaculatory dysfunction, female genital disorders (e.g., anorgasmia or difficulty reaching climax/orgasm), sweating.1 2 3 24 76

Interactions for Paxil

Metabolized partially by CYP2D6.1 Inhibits the activity of CYP2D6 and to a lesser extent CYP3A4.1 91

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6 or CYP3A4: possible increased plasma concentrations of the substrates.1 91 277

Use with caution and consider reducing dosage of concomitantly administered CYP2D6 substrate, particularly those with a narrow therapeutic index, such as TCAs, class IC antiarrhythmics, and some phenothiazines.1 91 277

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes (e.g., CYP2D6): potential pharmacokinetic interaction (altered paroxetine metabolism and plasma concentrations).a

Drugs Associated with Serotonin Syndrome

Potentially life-threatening serotonin syndrome with other serotonergic drugs.611 If concomitant use of other serotonergic drugs with paroxetine is clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases.611

If serotonin syndrome occurs, immediately discontinue paroxetine and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment.611 (See Serotonin Syndrome under Cautions.)

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect hemostasis.1 6 147 323 312 324 325 Use with caution.1

Specific Drugs

Drug

Interaction

Comments

Alcohol

Does not potentiate cognitive and motor effects of alcohol;1 2 3 6 19 24 146 possible serotonergically mediated pharmacodynamic interaction in CNS146

Avoid concomitant use1

Amphetamines

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, the amphetamine, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Antacids

Pharmacokinetic interactions unlikely6 19 92

Antiarrhythmic agents, class IC (e.g., encainide, flecainide, propafenone)

Possible inhibition of metabolism by paroxetinea

Use cautiona

Antidepressants, other SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline) or SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine)

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, the SSRI or SNRI, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Antidepressants, tricyclics (TCAs) (e.g., desipramine, imipramine)

Increased peak plasma concentrations, AUC, and elimination half-life of TCA1

Potentially life-threatening serotonin syndrome611

Use with caution1

May need to monitor plasma tricyclic concentrations; consider reducing tricyclic dosage1

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, the TCA, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Atomoxetine

Increased peak plasma concentrations and AUCs of atomoxetine1 312 335 336

Pharmacokinetics of paroxetine not affected335

Consider initiating atomoxetine in a reduced dosage and adjust atomoxetine dosage if necessary1 312

Benzodiazepines (e.g., diazepam, lorazepam, oxazepam)

Pharmacokinetic or pharmacologic interactions unlikely1 6 147 148

Buspirone

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, buspirone, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Cimetidine

Increased plasma paroxetine concentrations1 147 262

Adjust paroxetine dosage as needed1

Clozapine

Possible increases in plasma clozapine concentrations286

Use with caution and monitor closely

Adjust dosage as needed286

Digoxin

Digoxin AUC reduced by 15%; limited clinical experience to date1

Use with caution1

Fentanyl

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, fentanyl, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

5-HT1 receptor agonists (triptans; e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, the triptan, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Linezolid

Potentially life-threatening serotonin syndrome402 611

Do not use concurrently;402 consider availability of alternative anti-infectives and weigh benefit of linezolid against risk of serotonin syndrome402 611

If emergency use of linezolid is considered necessary, immediately discontinue paroxetine; monitor closely for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first402 611

May resume paroxetine 24 hours after last linezolid dose402 611

If nonemergency use of linezolid is planned, withhold paroxetine for at least 2 weeks prior to initiating linezolid402

Do not initiate paroxetine in patients receiving linezolid402 611

If urgent treatment of a psychiatric condition is necessary, consider other interventions, including hospitalization; may initiate paroxetine 24 hours after last linezolid dose402 611

Lithium

Potentially life-threatening serotonin syndrome611

Pharmacokinetic interaction unlikely611

If concomitant use clinically warranted, exercise caution and advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, lithium, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

MAO inhibitors

Potentially life-threatening serotonin syndrome611

Concomitant use contraindicated611

Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor intended to treat psychiatric disorders and initiation of paroxetine, and vice versa611

Methylene blue

Potentially life-threatening serotonin syndrome404 405 611

Most cases occurred when methylene blue was used as a diagnostic (visualizing) dye (1–8 mg/kg IV) during parathyroid surgery; unclear whether there is a risk of serotonin syndrome when methylene blue is administered by other routes or in lower IV doses in patients receiving serotonergic drugs404 405 611

Generally should not use methylene blue in patients receiving paroxetine; 404 consider availability of alternative interventions and weigh benefits of IV methylene blue against risk of serotonin syndrome404 611

If emergency use of IV methylene blue is considered necessary, immediately discontinue paroxetine and monitor for symptoms of serotonin syndrome for 2 weeks or until 24 hours after last methylene blue dose, whichever comes first404 611

May resume paroxetine 24 hours after last dose of IV methylene blue404 611

If nonemergency use of methylene blue is planned, withhold paroxetine for at least 2 weeks prior to initiating methylene blue404

Do not initiate paroxetine in patients receiving IV methylene blue404 611

If urgent treatment of a psychiatric condition is necessary, consider other interventions, including hospitalization; may initiate paroxetine 24 hours after last IV methylene blue dose404 611

Metoprolol

Severe hypotension possible1

Use with caution50 264 271

NSAIAs (e.g., aspirin)

Increased risk of bleeding1 323 312 324 325

Use caution1

Perphenazine

Possible inhibition of metabolism by paroxetine1

Use caution1

Phenobarbital

Decreased AUC and elimination half-life of paroxetine1

Adjust dosage as needed1

Phenytoin

Decreased AUC and elimination half-life of paroxetine and increased plasma phenytoin concentration1

Adjust dosages as needed1

Pimozide

Increased AUC and peak plasma concentrations of pimozide1 312

Possible increased risk of QT-interval prolongation1 312

Concomitant use contraindicated1 312

Procyclidine

Increased plasma procyclidine concentrations 1

If anticholinergic effects are seen, decrease procyclidine dosage1

Propranolol

Paroxetine did not affect plasma propranolol concentrations; effects of propranolol on plasma paroxetine concentrations not evaluated1

Protein-bound drugs

Potential for displacement of paroxetine or other protein-bound drugs from binding sites1

Monitor patients for potential adverse effects 1

Risperidone

Increased plasma risperidone concentrations, decreased plasma 9-hydroxyrisperidone (active metabolite) concentrations, and increased plasma concentrations of active moiety (risperidone plus 9-hydroxyrisperidone)1 322

Generally well tolerated; possible risk of parkinsonian symptoms322

Carefully monitor patients; consider monitoring plasma risperidone concentrations322

Consider lower initial dosage of paroxetine (10–20 mg daily)322

St. John's wort (Hypericum perforatum)

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, St. John's wort, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Thioridazine

Potentially serious or fatal reaction (e.g., torsade de pointes)1

Concomitant use contraindicated1

Tramadol

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, tramadol, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Tryptophan

Potentially life-threatening serotonin syndrome611

If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases611

If serotonin syndrome occurs, immediately discontinue paroxetine, tryptophan, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment611

Warfarin

Possible increased risk of bleeding1 6 147

Use with caution1

Paxil Pharmacokinetics

Absorption

Bioavailability

Completely absorbed following oral administration.1

Oral bioavailability in humans not fully elucidated to date.1

Equally bioavailable from commercially available conventional tablets and suspension.a

Food

Food does not substantially affect the absorption of paroxetine.19 92

Special Populations

In geriatric patients, trough paroxetine concentrations are 70–80% greater than in younger patients.1

In patients with renal impairment (Clcr <30 mL/minute), mean plasma paroxetine concentrations are approximately 4 times greater than those seen in healthy individuals.1

Hepatic impairment may increase plasma concentrations twofold.1

Distribution

Extent

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

Plasma Protein Binding

≥93%1

Elimination

Metabolism

Extensively metabolized, 1 94 partially by CYP2D6.1 Metabolites are essentially inactive.1 6 84 Inhibits activity of CYP2D6.1 91

Elimination Route

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

Half-life

Averages approximately 21–24 hours.1 3 4 5 6 19 83 89

Special Populations

In geriatric individuals, elimination half-life may be increased (e.g., to about 36 hours).3 83

Stability

Storage

Oral

Conventional Tablets

15–30°C.1

Extended-release Tablets

≤25°C.304

Suspension

≤25°C.1 304

Actions

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

  • Has little or no effect on other neurotransmitters1 4 6 84 or any clinically important anticholinergic, antihistaminic, or adrenergic (α1, α2, β) blocking activity at usual therapeutic dosages.1 4 84 85

  • Generally less sedating than most older antidepressants.1 2 3 18 19 24 62 72 73

Advice to Patients

  • Importance of providing copy of written patient information (medication guide) each time paroxetine is dispensed.314 315 320 611 Importance of advising patients to read the patient information before taking paroxetine and each time the prescription is filled.611

  • Risk of suicidality; importance of patients, caregivers, and families being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.314 315 320 611 (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Potential risk of serotonin syndrome, particularly with concurrent use of paroxetine and 5-HT1 receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents.611 Importance of immediately contacting clinician if manifestations of serotonin syndrome develop (e.g., restlessness, hallucinations, delirium, loss of coordination, fast heart beat, increased body temperature, sweating, muscle stiffness, labile BP, diarrhea, coma, nausea, vomiting, confusion).611

  • Importance of continuing therapy even if improvement is not evident for 4 weeks, unless directed otherwise by clinician.1 3

  • Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until effects on the individual are known.1 3

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, or of use of alcohol-containing beverages or products.1 3

  • Risk of fetal harm.337 338 343 358 611 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.611 If a woman becomes pregnant while receiving paroxetine, inform her of the potential hazard to the fetus.337 338 343 358 Unless the potential benefits to the mother justify continuing treatment, consider either discontinuing paroxetine therapy or switching to another antidepressant.337 338 343 358 For women who intend to become pregnant or are in their first trimester of pregnancy, initiate paroxetine only after consideration of other available treatment options.337 338 343 358 (See Pregnancy under Cautions.)

  • Importance of informing patients of other important precautionary information.1 3 (See Cautions.)

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

PARoxetine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

10 mg (of paroxetine) per 5 mL

Paxil (with parabens, propylene glycol, saccharin sodium, and sorbitol)

GlaxoSmithKline

Tablets, extended-release, film-coated

12.5 mg (of paroxetine)

Paxil CR

GlaxoSmithKline

25 mg (of paroxetine)

Paxil CR

GlaxoSmithKline

37.5 mg (of paroxetine)

Paxil CR

GlaxoSmithKline

Tablets, film-coated

10 mg (of paroxetine)*

Paxil (scored)

GlaxoSmithKline

20 mg (of paroxetine)*

Paxil (scored)

GlaxoSmithKline

30 mg (of paroxetine)*

Paxil

GlaxoSmithKline

40 mg (of paroxetine)*

Paxil

GlaxoSmithKline

AHFS DI Essentials. © Copyright 2017, Selected Revisions April 14, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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