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)

Special Alerts:

[Posted 12/14/2011] ISSUE: FDA notified healthcare professionals and the public on the use of selective serotonin reuptake inhibitor (SSRI) antidepressants by women during pregnancy and the potential risk of a rare heart and lung condition known as Persistent Pulmonary Hypertension of the Newborn (PPHN). The initial Public Health Advisory in July 2006 on this potential risk was based on a single published study. Since then, there have been conflicting findings from new studies evaluating this potential risk, making it unclear whether use of SSRIs during pregnancy can cause PPHN.

FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN. FDA will update the SSRI drug labels to reflect the new data and the conflicting results.

BACKGROUND: SSRIs are marketed under various brand and generic drug names, and are used to treat depression and other psychiatric disorders. There are no adequate and well-controlled studies of SSRIs in pregnant women.

PPHN occurs when a newborn baby does not adapt to breathing outside the womb. Newborns with PPHN may require intensive care support including a mechanical ventilator to increase their oxygen level. If severe, PPHN can result in multiple organ damage, including brain damage, and even death.

RECOMMENDATION: FDA advises health care professionals not to alter their current clinical practice of treating depression during pregnancy. See the Data Summary in the FDA Drug Safety Communication for additional information. FDA will communicate any new information on the risk of bleeding and dabigatran when it becomes available. For more information visit the FDA website at: and .

[Posted 05/02/2007] FDA notified healthcare professionals that the Agency proposed that makers of all antidepressant medications update the existing black box warning on the prescribing information for their products to include warnings about the increased risks of suicidal thinking and behavior in young adults ages 18 to 24 years old during the first one to two months of treatment. The proposed labeling changes also state that scientific data did not show this increased risk in adults older than 24 years of age and that adults 65 years of age and older taking antidepressants have a decreased risk of suicidality. The proposed updates apply to the entire category of antidepressants. Individuals currently taking prescribed antidepressant medications should not stop taking them and should notify their healthcare professional if they have concerns. Manufacturers of antidepressant medications will have 30 days to submit their revised product labeling and revised Medication Guides to FDA for review. See the FDA press release for the list of products affected by the proposed antidepressant product labeling changes. For more information visit the FDA website at: , and .

[Posted 07/19/2006] FDA notified healthcare professionals and consumers of important information from two recent studies that should be considered when making treatment decisions in pregnant women who take antidepressants. The studies included pregnant women who were treated with selective serotonin reuptake inhibitors (SSRIs), or in a few cases, other antidepressant medications.

One study illustrated the potential risk of relapsed depression after stopping antidepressant medication during pregnancy. In this study, women who stopped their medicine were five times more likely to have a relapse of depression during their pregnancy than were women who continued to take their antidepressant medicine while pregnant.

The second study suggests there may be additional, though rare, risks of taking SSRI medications during pregnancy. This study focused on newborn babies with persistent pulmonary hypertension (PPHN), which is a serious and life-threatening lung condition that occurs soon after birth. Babies born with PPHN have high pressure in their lung blood vessels and are not able to get enough oxygen into their bloodstream. In this study, PPHN was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week of pregnancy compared to babies whose mothers did not take an antidepressant. The study was too small to compare the risk of one drug compared to another. The finding of PPHN in babies of mothers who used a SSRI antidepressant in the second half of pregnancy adds to concerns from previous reports that infants of mothers taking SSRIs late in pregnancy may experience difficulties such as irritability, difficulty feeding and in very rare cases, difficulty breathing.

Additionally, the labeling for paroxetine (Paxil) was recently changed to add information about findings in an epidemiologic study that suggests that exposure to the drug in the first trimester of pregnancy may be associated with an increased risk of cardiac birth defects.

Women who are pregnant or thinking about becoming pregnant should not stop any antidepressant medication without first consulting their physician. The FDA is seeking additional information about the possible risk of PPHN in newborn babies of mothers who took SSRI antidepressants in pregnancy. FDA has asked the sponsors of all SSRIs to change prescribing information to describe the potential risk for PPHN. For more information visit the FDA website at: and .

[Posted 07/19/2006] FDA notified healthcare professionals and consumers of new safety information regarding taking medications used to treat migraine headaches (triptans) together with certain types of antidepressant and mood disorder medications (selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs). A life-threatening condition called serotonin syndrome may occur when triptans are used together with a SSRI or a SNRI.

Serotonin syndrome occurs when the body has too much of a chemical found in the nervous system (serotonin). Each of the above medications (triptans, SSRIs, and SNRIs), cause an increase in serotonin levels. Symptoms of serotonin syndrome may include restlessness, hallucinations, loss of coordination, fast heart beat, rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting, and diarrhea.

Healthcare professionals prescribing a triptan, SSRI or SNRI should keep in mind that triptans are often used intermittently and either the triptan, SSRI or SNRI may be prescribed by a different physician; weigh the potential risk of serotonin syndrome with the expected benefit of using the above combination; discuss the possibility of serotonin syndrome with patients if a triptan and an SSRI or SNRI will be used together; and follow patients closely during treatment if a triptan and an SSRI or SNRI are used together.

Patients taking a triptan along with an SSRI or SNRI should talk to their doctor before stopping their medication and should immediately seek medical attention if they experience any of the above symptoms. FDA requested that all manufacturers of triptans, SSRIs and SNRIs update their prescribing information to warn of the possibility of serotonin syndrome when these medications are taken together. For more information visit the FDA website at: and .

Warning(s)

  • Suicidality in Children and Adolescents
  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders (see Pediatric Use under Cautions); balance this risk with clinical need.1 311 312 314 315 Paroxetine is not approved for use in pediatric patients.1 312

  • Closely monitor pediatric 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.1 312 314 (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

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

Uses for Paxil

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Major Depressive Disorder

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Slideshow: Depression, the Risk of Suicide, and Treatment Options

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 and initiation of paroxetine, and vice versa.1

  • Monitor for possible worsening of depression or suicidality, especially at the beginning of therapy or during periods of dosage adjustments.1 312 314 (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 monitor periodically 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.)

  • Consider cautiously tapering dosage during third trimester of pregnancy prior to delivery.1 312 329 330 331 332 (See Pregnancy 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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Adults

Major Depressive Disorder

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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 increments of 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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

  • Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor.1 5

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

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

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

Warnings/Precautions

Warnings

Drug Interactions

Concomitant use of some SSRIs with MAO inhibitor associated with serious, sometimes fatal reactions, including manifestations resembling serotonin syndrome (e.g., hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes) or neuroleptic malignant syndrome (NMS).1 (See Contraindications.)

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

Worsening of Depression and Suicidality Risk

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) in both adult and pediatric patients with major depressive disorder; may persist until clinically important remission occurs with therapy.1 312 314

Possible increased risk of suicidal behavior in young adult patients (18–30 years of age), particularly those with major depressive disorder.a b c Increased risk of suicidal behavior and thoughts in patients with a history of suicidal behavior or thoughts and in patients exhibiting a substantial degree of suicidal ideation prior to initiating therapy.a b c Increased risk of suicidal behavior was observed despite evidence of paroxetine efficacy in patients being treated for major depressive disorder.b

Closely supervise pediatric patients receiving paroxetine for any reason and adult patients with major depressive disorder or other psychiatric illness with comorbid depression during initiation of therapy and during periods of dosage adjustments.1 312 314 (See Boxed Warning.) Carefully monitor all patients, particularly young adults and those that are improving, during paroxetine therapy regardless of the condition being treated.b

If anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and/or mania occur, consider changing or discontinuing therapy, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.1 312 314 If decision is made to discontinue therapy, taper paroxetine dosage as rapidly as is feasible but consider risks of abrupt discontinuance.1 312 314 (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.1 312 314

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.1 312 314

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

Fetal/Neonatal Morbidity and Mortality

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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 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 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 selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs) late in the third trimester; may arise immediately upon delivery.1 312 327 328 329 330 331 332

Increased risk of persistent pulmonary hypertension of the newborn (PPHN) in infants exposed to SSRIs during late pregnancy; associated with substantial neonatal morbidity and mortality.a c

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 Consider cautiously tapering dose during third trimester prior to delivery.1 312 329 330 331 332

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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category D.337 338 a c See Fetal/Neonatal Morbidity and Mortality under Cautions.

Lactation

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

Pediatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, obsessive-compulsive disorder, or other psychiatric disorders based on pooled analyses of short-term placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).1 312 314 315 No suicides occurred in these trials.1 312 314 315 If considering use of paroxetine in a child or adolescent, balance potential risks with clinical need.1 311 312 314 315 (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

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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Potential pharmacodynamic interaction (serotonin syndrome).1 229 230 231 232 233 234 235 Although usually mild, serious complications and death occasionally have been reported.1 230 231 233 236 237 238 239 Serotonin syndrome most commonly occurs when serotonergic agents with different mechanisms of action are given concurrently or in close succession.230 231 233 236 237 Avoid such use, or use with caution.237 239

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

Antacids

Pharmacokinetic interactions unlikely6 19 92

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

Possible inhibition of metabolism by paroxetinea

Use cautiona

Antidepressants, tricyclic (TCA)

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

Use with caution1

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

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

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

Lithium

Pharmacokinetic or pharmacodynamic interactions unlikely1

Use with caution1

MAO inhibitors (e.g., isoniazid, moclobemide, selegiline)

Potentially serious or fatal serotonin syndrome or NMS1 196 230 233 234 249

Concomitant use contraindicated1 5

Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of paroxetine, and vice versa1 5

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

Carefullly monitor patients; consider monitoring plasma risperidone concentrations322

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

Sumatriptan

Weakness, hyperreflexia, incoordination, progressive agitation, tingling, chest pain, and/or dyspnea1 243

Monitor patient 1

Theophylline

Increased serum theophylline concentrations1

Monitor for theophylline toxicity1

Thioridazine

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

Concomitant use contraindicated1

Tryptophan

Adverse effects resembling serotonin syndrome1

Avoid concomitant use1

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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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

  • Risk of suicidalility; importance of patients, caregivers, and families immediately reporting emergence of suicidality, worsening depression, or other manifestations associated with increased risk of worsening depression or suicidality.1 312 314 320 FDA recommends providing written patient information (medication guide) explaining risks in pediatric patients each time the drug is dispensed.314 320

  • 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

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 3

  • 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.

* 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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

PARoxetine HCl 10MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$29.99 or 90/$79.97

PARoxetine HCl 12.5MG 24-hr Tablets (MYLAN): 30/$102.67 or 90/$277.32

PARoxetine HCl 20MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$15.99 or 60/$23.97

PARoxetine HCl 25MG 24-hr Tablets (MYLAN): 30/$105.86 or 90/$289.01

PARoxetine HCl 30MG Tablets (MYLAN): 30/$35.99 or 90/$89.97

PARoxetine HCl 37.5MG 24-hr Tablets (APOTEX): 30/$107.99 or 90/$296.44

PARoxetine HCl 40MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$24.99 or 90/$59.95

Paxil 10MG/5ML Suspension (APOTEX): 250/$189.98 or 750/$539.94

Paxil 10MG Tablets (APOTEX): 30/$116.99 or 90/$320.98

Paxil 20MG Tablets (APOTEX): 30/$125.99 or 90/$349.96

Paxil 30MG Tablets (APOTEX): 30/$129.99 or 90/$369.97

Paxil 40MG Tablets (APOTEX): 30/$136.99 or 90/$384.94

Paxil 40MG Tablets (APOTEX): 30/$136.99 or 90/$384.95

Paxil CR 12.5MG 24-hr Tablets (APOTEX): 30/$120.00 or 90/$335.96

Paxil CR 25MG 24-hr Tablets (APOTEX): 30/$139.98 or 90/$383.95

Paxil CR 37.5MG 24-hr Tablets (APOTEX): 30/$141.99 or 90/$411.97

Pexeva 20MG Tablets (NOVEN THERAPEUTICS): 30/$190.98 or 90/$528.95

Pexeva 30MG Tablets (NOVEN THERAPEUTICS): 30/$200.98 or 90/$584.96

Pexeva 40MG Tablets (NOVEN THERAPEUTICS): 30/$205.99 or 90/$572.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

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