Paroxetine   
(Copyright 1997 - Mosby, Inc.)

Table of Contents

Categories: Antidepressants; Central Nervous System Agents; Depression; Depressive Disorder; Fatigue; Psychotherapeutic Agents; Selective Serotonin Reuptake Inhibitors; Panic Disorder^*; Pregnancy Category B; FDA Class 1S ("Standard Review"); Sales > $500 Million; FDA Approved 1992 Dec; Top 200 Drugs
* Indication not approved by the FDA

Brand Names: Aropax; Aropax 20; Paxil; Seroxat
(Foreign brand names outside U.S. in italics)

Formularies: BC-BS; Medi-Cal; PCS

Cost of Therapy: $170.91 (Depression; Tablet; 20 mg; 1/day; 90 days) vs. Potential Cost of $2,576.38 (DRG 426, Depression)

Primary ICD9: 311 (Depressive Disorder, Not Elsewhere Classified)

Table of Contents:

Description
Clinical Pharmacology
Clinical Studies
Indications and Usage
Contraindications
Warnings
Precautions
Drug Interactions
Adverse Reactions
Drug Abuse and Dependence
Overdosage
Dosage and Administration
Patient Information
How Supplied
How Supplied - Equivalents Not Available

Description:

Paxil (paroxetine hydrochloride) is an orally administered antidepressant with a chemical structure unrelated to other selective serotonin reuptake inhibitors or to tricyclic, tetracyclic or other available antidepressants agents. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)-trans-4R-(4'-fluorophenyl)-3S-[(3',4'-methylenedioxyphenoxy) methyl] piperidine hydrochloride hemihydrate and has the empirical formula of C₁₉H₂₀FNO₃·HCl·1/2H₂O. The molecular weight is 374.8 (329.4 as free base).

Paroxetine hydrochloride is an odorless, off-white powder, having a melting point range of 120 to 138°C and a solubility of 5.4 mg/ml in water.

Each film-coated tablet contains paroxetine hydrochloride equivalent to paroxetine as follows: 20 mg-pink (scored); 30 mg-blue. Inactive ingredients consist of dibasic calcium phosphate dihydrate, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycols, polysorbate 80, sodium starch glycolate, titanium dioxide and one or more of the following: D&C Red No. 30, FD&C Blue No. 2.

Clinical Pharmacology:

Pharmacodynamics: The antidepressant action of paroxetine is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitroradioligand binding studies indicate that paroxetine has little affinity for muscarinic alpha₁-, alpha₂-, beta-adrenergic-, dopamine (D₂)-, 5-HT₁-, 5-HT₂,- and histamine (H₁)-receptors; antagonism of muscarinic, histaminergic, and alpha₁-adrenergic receptors has been associated with various anticholinergic, sedative and cardiovascular effects for other psychotropic drugs.

Because the relative potencies of paroxetine's major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

Pharmacokinetics: Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n=15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it might take substantially longer in an occasional patient. At steady state, mean values of C_max, T_max, C_min, and T_1/2were 61.7 ng/ml (CV 45%), 5.2 hr. (CV (10%), 30.7 ng/ml (CV 67%) and 21.0 hr. (CV 32%), respectively. The steady-state C_max and C_min values were about 6 and 14 times what would be predicted from a single-dose studies. Steady-state drug exposure based on AUC_0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that one of the enzymes that metabolizes paroxetine is readily saturable.

In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 to 40 mg daily for the elderly and 20 to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C_min values after 20 mg daily, values after 40 mg were only about 2 to 3 times greater than doubled.

Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with gluconic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by cytochrome P₄₅₀IID₆. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions (see PRECAUTIONS.)

Approximately 64% of a 30 mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period.

Distribution: Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma.

Protein Binding: Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/ml and 400 ng/ml, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/ml. Paroxetine does not alter the in vitroprotein binding of phenytoin or warfarin.

Renal and Liver Disease: Increased plasma concentrations of paroxetine occur in subjects with renal and hepatic impairment. The mean plasma concentrations in patients with creatinine clearance below 30 ml/min was approximately 4 times greater than seen in normal volunteers. Patients with creatinine clearance of 30 to 60 ml/min and patients with hepatic functional impairment had about a 2-fold increase in plasma concentrations (AUC, C_max).

The initial dosage should therefore be reduced in patients with severe renal or hepatic impairment, and upward titration, if necessary, should be at increased intervals (see DOSAGE AND ADMINISTRATION.)

Elderly Patients: In a multiple-dose study in the elderly at daily paroxetine doses of 20, 30 and 40 mg, C_minconcentrations were about 70% to 80% greater than the respective C_minconcentrations in nonelderly subjects. Therefore the initial dosage in the elderly should be reduced. (See DOSAGE AND ADMINISTRATION.)

Clinical Studies:

Depression: The efficacy of paroxetine hydrochloride as a treatment for depression has been established in 6 placebo-controlled studies of patients with depression (ages 18 to 73). In these studies paroxetine hydrochloride was shown to be significantly more effective than placebo in treating depression by at least 2 of the following measures: Hamilton Depression Rating Scale (HDRS), the Hamilton depressed mood item, and the Clinical Global Impression (CGI)--Severity of illness. Paroxetine hydrochloride was significantly better than placebo in improvement of the HDRS sub-factor scores, including the depressed mood item, sleep disturbance factor and anxiety factor.

A study of depressed outpatients who had responded to paroxetine hydrochloride (HDRS total score <8) during an initial 8-week open-treatment phase and were then randomized to continuation on paroxetine hydrochloride or placebo for 1 year demonstrated a significantly lower relapse rate for patients taking paroxetine hydrochloride (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients.

Obsessive Compulsive Disorder: The effectiveness of paroxetine hydrochloride in the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 12-week multicenter placebo-controlled studies of adult outpatients (Studies 1 and 2). Patients in all studies had moderate to severe OCD (DSM-IIIR) with mean baseline ratings on the Yale Brown Obsessive Compulsive Scale (YBOCS) total score ranging from 23 to 26. Study 1, a dose-range finding study where patients were treated with fixed doses of 20, 40 or 60 mg of paroxetine/day demonstrated that daily doses of paroxetine 40 and 60 mg are effective in the treatment of OCD. Patients receiving doses of 40 and 60 mg paroxetine experienced a mean reduction of approximately 6 and 7 points respectively on the YBOCS total score which was significantly greater than the approximate 4 point reduction at 20 mg and a 3 point reduction in the placebo-treated patients. Study 2 was a flexible dose study comparing paroxetine (20 to 60 mg daily) with clomipramine (25 to 250 mg daily). In this study, patients receiving paroxetine experienced a mean reduction of approximately 7 points on the YBOCS total score which was significantly greater than the mean reduction of approximately 4 points in the placebo-treated patients.

The following table provides the outcome classification by treatment group on Global Improvement items of the Clinical Global Impressions (CGI) scale for Study 1.

TABLE 1 - Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender.

The long-term maintenance effects of paroxtein hydrochloride in OCD were demonstrated in a long-term extension to Study 1. Patients who were responders on paroxetine during the 3-month double-blind phase and a 6-month extension on open-label paroxetine (20 to 60 mg/day) were randomized to either paroxetine or placebo in a 6-month double-blind relapse prevention phase. Patients randomized to paroxetine were significantly less likely to relapse than comparably treated patients who were randomized to placebo.

Panic Disorder: The effectiveness of paroxetine hydrochloride in the treatment of panic disorder was demonstrated in three 10 to 12 week multicenter, placebo-controlled studies of adult outpatients (Studies 1-3). Patients in all studies had panic disorder (DSM-IIIR), with or without agoraphobia. In these studies, paroxetine hydrochloride was shown to be significantly more effective than placebo in treating panic disorder by at least 2 out of 3 measures of panic attack frequency and on the Clinical Global Impression Severity of Illness score.

Study 1 was a 10-week dose-range finding study: patients were treated with fixed paroxetine doses of 10, 20, or 40 mg/day or placebo. A significant difference from placebo was observed only for the 40 mg/day group. At endpoint, 76% of patients receiving paroxetine 40 mg/day were free of panic attacks, compared to 44% of placebo-treated patients.

Study 2 was a 12-week flexible-dose study comparing paroxetine (10 to 60 mg daily) and placebo. At endpoint, 51% of paroxetine patients were free of panic attacks compared to 32% of placebo-treated patients.

Study 3 was a 12-week flexible-dose study comparing paroxetine (10 to 60 mg daily) to placebo in patients concurrently receiving standardized cognitive behavioral therapy. At endpoint, 33% of the paroxetine-treated patients showed a reduction to 0 or 1 panic attacks compared to 14% of placebo patients.

In both Studies 2 and 3, the mean paroxetine dose for completers at endpoint was approximately 40 mg/day of paroxetine.

In both Studies 2 and 3, the mean paroxetine dose for completers at endpoint was approximately 40 mg/day of paroxetine.

Long-term maintenance effects of paroxetine hydrochloride in panic disorder were demonstrated in an extension to Study 1. Patients who were responders during the 10-week double-blid phase and during a 3-month double-blind extension phase were randomized to either paroxetine (10, 20, or 40 mg/day) or placebo in a 3-month double-blind relapse prevention phase. Patients randomized to paroxetine were significantly less likely to relapse than comparably treated patients who were randomized to placebo.

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender.

Indications and Usage:

Depression

Paroxetine hydrochloride is indicated for the treatment of depression.

The efficacy of paroxetein hydrochloride in the treatment of a major depressive episode was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the DSM-III category of major depressive disorder (See CLINICAL PHARMACOLOGY.)

A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sex drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.

The antidepressant action of paroxetine hydrochloride in hospitalized depressed patients has not been adequately studied.

The efficacy of paroxetine hydrochloride in maintaining an antidepressant response for up to 1 year was demonstrated in a placebo-controlled trial (see CLINICAL PHARMACOLOGY.)

Nevertheless, the physician who elects to use paroxetine hydrochloride for extended periods should periodically re-evaluate for long-term usefulness of the drug for the individual patient.

Obsessive Compulsive Disorder

Paroxetine hydrochloride is indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) as defined in the DSM-IV. The obsessions or compulsions cause marked distress, are time-consuming, or significantly interfere with social or occupational functioning.

The efficacy of paroxetine hydrochloride was established in two 12 week trials with obsessive compulsive outpatients whoe diagnoses corresponded most closely to the DSM-IIIR category of obsessive compulsive disorder (see CLINICAL STUDIES.)

Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses or images (obsessions) that are egodystonic and/or repetitive, purposeful and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable.

Long-term maintenance of efficacy was demonstrated in a 6-month relapse prevention trial. In this trial, patients assigned to paroxetine showed a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY.) Nevertheless, the physicians who elects to use paroxetine hydrochloride for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION.)

Panic Disorder

Paroxetine hydrochloride is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks.

The efficacy of paroxetine hydrochloride was established in three 10 to 12 week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder (see CLINICAL STUDIES.)

Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks (i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: [(1) palpitations; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded, or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flashes.])

Long-term maintenance of efficacy was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY.) Nevertheless, the physician who prescribes paroxetine hydrochloride for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Contraindications:

Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated (see WARNINGS.)

Warnings:

Potential for Interaction with Monoamine Oxidase Inhibitors.

In patients receiving another serotonin reuptake inhibitor drug in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued that drug and have been started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. While there are no human data showing such an interaction with paroxetine, limited animal data on the effects of combined use of paroxetine and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that paroxetine hydrochloride not be used in combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI. At least 2 weeks should be allowed after stopping paroxetine before starting a MAOI.

Precautions:

General

Activation of Mania/Hypomania: During premarketing testing, hypomania or mania occurred in approximately 1.0% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. In a subset of patients classified as bipolar, the rate of manic episodes was 2.2% for paroxetine and 11.6% for the combined active-control groups. As with all antidepressants, paroxetine should be used cautiously in patients with a history of mania.

Seizures: During premarketing testing, seizures occurred in 0.1% of paroxetine-treated patients, a rate similar to that associated with other antidepressants. Paroxetine should be used cautiously in patients with a history of seizures. It should be discontinued in any patient who develops seizures.

Suicide: The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for paroxetine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Hyponatremia: Several cases of hyponatremia have been reported. The hyponatremia appeared to be reversible when paroxetine was discontinued. The majority of these occurrences have been in elderly individuals, some in patients taking diuretics or who were otherwise volume depleted.

Abnormal Bleeding: There have been several reports of abnormal bleeding (mostly ecchymosis and purpural) associated with paroxetine treatment, including a report of impaired platelet aggregation. While a causal relationship to paroxetine is unclear, impaired platelet aggregation may result from platelet serotonin depletion and contribute to such occurrences.

Use in Patients with Concomitant Illness: Clinical experience with paroxetine hydrochloride in patients with certain concomitant systemic illness is limited. Caution is advisable in using paroxetine hydrochloride in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Paroxetine hydrochloride has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from clinical studies during the product's premarket testing. Evaluations of electrocardiograms of 682 patients who received paroxetein hydrochloride in double-blind, placebo-controlled trials, however, did not indicate that paroxetine hydrochloride is associated with the development of significant ECG abnormalities. Similarly, paroxetine hydrochloride does not cause any clinically important changes in heart rate or blood pressure.

Increased plasma concentrations of paroxetine occur in patients with severe renal impairment (creatinine clearance <30 ml/min.) or severe hepatic impairment. A lower starting dose should be used in such patients (see DOSAGE AND ADMINISTRATION.)

Information for Patients

Physicians are advised to discuss the following issues with patients for whom they prescribe paroxetine hydrochloride.

Interference with Cognitive and Motor Performance: Any psychoactive drug may impair judgment, thinking or motor skills. Although in controlled studies paroxetine hydrochloride has not been shown to impair psychomotor performance, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that paroxetine hydrochloride therapy does not affect their ability to engage in such activities.

Contemplating Course of Therapy: While patients may notice improvement with paroxetine hydrochloride therapy in 1 to 4 weeks, they should be advised to continue therapy as directed.

Concomitant Medication: Patients should be advised to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.

Alcohol: Although paroxetine hydrochloride has not been shown to increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid alcohol while taking paroxetine hydrochloride.

Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.

Nursing: Patients should be advised to notify their physician if they are breast-feeding an infant. See PRECAUTIONS, Nursing Mothers.

Laboratory Tests There are no specific laboratory tests recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Two-year carcinogenicity studies were conducted in mice and rats given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5 and 20 mg/kg/day (rats). The maximum doses in these studies were approximately 25 (mouse) and 20 (rat) times the maximum dose recommended for human use on a mg/kg basis or 2.5 (mouse) and 5.8 (rat) times the maximum recommended human dose on a mg/m² basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50 and 4/50 for control, low-, middle- and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown.

Mutagenesis: Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivoin mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats.

Impairment of Fertility: Serotonergic compounds are known to affect reproductive function in animals. Impaired reproductive function (i.e., reduced pregnancy rate, increased pre- and post- implantation losses, decreased viability of pups) was found in reproduction studies in rats at doses of paroxetine which were 15 or more times the highest recommended human dose on a mg/kg basis, or 4.4 times on a mg/m²basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 to 52 weeks. These lesions, which consisted of vacuolation of epididymal tubular epithelium and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis occurred at doses which were 25 times the highest recommended human dose on a mg/kg basis of 7.3 times on a mg/m² basis.

Pregnancy Teratogenic Effects--Pregnancy Category C: Reproduction studies performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are equivalent to 9.7 (rat) and 2.2 (rabbit) times the maximum recommended human dose (MRHD) for depression (50 mg) and 8.1 (rat) and 1.9 (rabbit) times the MRHD for OCD, on a mg/m² basis. These studies have revealed no evidence of teratogenic effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day or 0.19 times (mg/m²) the MRHD for depression and at 0.16 times (mg/m²) the MRHD for OCD. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known. There are no adequate and well-controlled studies in pregnant women. Because animal reporduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of paroxetine on labor and delivery in humans is unknown.

Nursing Mothers: Like many other drugs, paroxetine is secreted in human milk, and caution should be exercised when paroxetine hydrochloride is administered to a nursing woman.

Usage in Children: Safety and effectiveness in children have not been established.

Geriatric Use: In worldwide paroxetine hydrochloride clinical trials, 17% of paroxetine hydrochloride- treated patients (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; there were, however, no overall differences in the adverse event profile between elderly and younger patients, and effectiveness was similar in younger and older patients. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.)

Drug Interactions:

Tryptophan: As with other serotonin reuptake inhibitors, an interaction between paroxetine and tryptophan may occur when they are co-administered. Adverse experiences, consisting primarily of headache, nausea, sweating and dizziness, have been reported when tryptophan was administered to patients taking paroxetine hydrochloride. Consequently, concomitant use of paroxetine hydrochloride with tryptophan is not recommended.

Monoamine Oxidase Inhibitors: (See CONTRAINDICATIONS) and WARNINGS.

Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction (that causes an increased bleeding diathesis in the face of unaltered prothrombin time) between paroxetine and warfarin. Since there is little clinical experience, the concomitant administration of paroxetine hydrochloride and warfarin should be undertaken with caution.

Drugs Affecting Hepatic Metabolism: The metabolism and pharmacokinetics of paroxetine may be affected by the induction or inhibition of drug-metabolizing enzymes.

Cimetidine: Cimetidine inhibits many cytochrome P₄₅₀ (oxidative) enzymes. In a study where paroxetine hydrochloride (30 mg q.d.) was dosed orally for 4 weeks, steady-state plasma concentrations of paroxetine were increased by approximately 50% during co-administration with oral cimetidine (300 mg t.i.d.) for the final week. Therefore, when these drugs are administered concurrently, dosage adjustment of paroxetine hydrochloride after the 20 mg starting dose should be guided by clinical effect. The effect of paroxetine on cimetidine's pharmacokinetics was not studied.

Phenobarbital: Phenobarbital induces many cytochrome P₄₅₀(oxidative) enzymes. When a single oral 30 mg dose of paroxetine hydrochloride was administered at phenobarbital steady state (100 mg q.d. for 14 days), paroxetine AUC and T_1/2were reduced (by an average of 25% and 38%, respectively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Since paroxetine hydrochloride exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the 2 drugs are both being chronically dosed. No initial paroxetine hydrochloride dosage adjustment is considered necessary when co- administered with phenobarbital; any subsequent adjustment should be guided by clinical effect.

Phenytoin: When a single oral 30 mg dose of paroxetine hydrochloride was administered at phenytoin steady state (300 mg q.d. for 14 days), paroxetine AUC and T_1/2 were reduced (by an average of 50% and 35%, respectively) compared to paroxetine hydrochloride administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg q.d. for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Since both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed. No initial dosage adjustments are considered necessary when these drugs are co- administered; any subsequent adjustments should be guided by clinical effect.

Drug Metabolized by Cytochrome P₄₅₀IID₆: Concomitant use of with drugs metabolized by cytochrome P₄₅₀IID₆ has not been formally studied but may require lower doses than usually prescribed for either paroxetine hydrochloride or the other drug. Many drugs, including most antidepressants (paroxetine, other SSRIs and many tricyclics), are metabolized by the cytochrome P₄₅₀ isozyme P₄₅₀IID₆. In most patients (>90%), this P₄₅₀IID₆ isozyme is saturated early during paroxetine hydrochloride dosing. Like other agents that are metabolized by P₄₅₀IID₆, paroxetine may significantly inhibit the activity of this isozyme.

Therefore, co-administration of paroxetine hydrochloride with other drugs that are metabolized by this isozyme, including certain antidepressants (e.g., nortriptyline, amitriptyline, imipramine, desipramine and fluoxetine), phenothiazines (e.g., thioridazine) and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution.

At steady state, when the P₄₅₀IID₆ pathway is essentially saturated, paroxetine clearance is governed by alternative P₄₅₀ isozymes which, unlike P₄₅₀IID₆, show no evidence of saturation. (see PRECAUTIONS, Tricyclic Antidepressants.

Drugs Metabolized by Cytochrome P₄₅₀IIIA₄: An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for cytochrome P₄₅₀IIIA₄, revealed no effect of paroxetine or terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of P₄₅₀IIIA₄ activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, astemizole, cisapride, triazolam, and cyclosporin. Based on the assumption that the relationship between paroxetine's in vitro K and its lack of effect on terfenadine's in vivo clearance predicts its effect on other IIIA₄ substrates, paroxetine's extent of inhibition of IIIA₄ activity is not likely to be of clinical significance.

Tricyclic Antidepressants (TCA): Caution is indicated in the co-administration of tricyclic antidepressants (TCAs) with paroxetine hydrochloride, because paroxetine may inhibit TCA metabolism. Plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced, if a TCA is co-administered with paroxetine hydrochloride (see PRECAUTIONS: Drugs Metabolized by Cytochrome P₄₅₀IID₅

Drugs Highly Bound to Plasma Protein: Because paroxetine is highly bound to plasma protein, administration of paroxetine hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse events. Conversely, adverse effects could result from displacement of paroxetine by other highly bound drugs.

Alcohol: Although paroxetine hydrochloride does not increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid alcohol while taking paroxetine hydrochloride.

Lithium: A multiple-dose study has shown that there is no pharmacokinetic interaction between paroxetine hydrochloride and lithium carbonate. However, since there is little clinical experience, the concurrent administration of paroxetine and lithium should be undertaken with caution.

Digoxin: The steady-state pharmacokinetics of paroxetine was not altered when administered with digoxin at steady state. Mean digoxin AUC at steady state decreased by 15% in the presence of paroxetine. Since there is little clinical experience, the concurrent administration of paroxetine and digoxin should be undertaken with caution.

Diazepam: Under steady-state conditions, diazepam does not appear to affect paroxetine kinetics. The effects of paroxetine on diazepam were not evaluated.

Procyclidine: Daily oral dosing of paroxetine hydrochloride (30 mg q.d.) increased steady-state AUC_0-24, C_Max and C_min values of procyclidine (5 mg oral q.d.) by 35%, 37%, and 67%, respectively, compared to procyclidine alone at steady state. If anticholinergic effects are seen, the dose of procyclidine should be reduced.

Beta-Blockers: In a study where propranolol (80 mg b.i.d.) was dosed orally for 18 days, the established steady-state plasma concentrations of propranolol were unaltered during co-administration with paroxetine hydrochloride (30 mg q.d.) for the final 10 days. The effects of propranolol on paroxetine have not been evaluated. See ADVERSE REACTIONS, Postmarketing Reports.

Theophylline: Reports of elevated theophylline levels associated with paroxetine hydrochloride treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered.

Electroconvulsive Therapy (ECT): There are no clinical studies of the combined use of ECT and paroxetine hydrochloride.

Adverse Reactions:

Associated with Discontinuation of Treatment Twenty-one percent (881/4,126) of paroxetine hydrochloride patients in worldwide clinical trials discontinued treatment due to an adverse event. The most common events (>=1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) included ( TABLE 1):

TABLE 1 -

Commonly Observed Adverse Events

Depression: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 2 below) were: asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.

Obsessive Compulsive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that of placebo, derived from Table 3 below) were: nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.

Panic Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 3 below) were: asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders and impotence.

Incidence in Controlled Clinical Trials

Depression: Table 2 enumerates adverse events that occurred at an incidence of 1% or more among paroxetine-treated patients who participated in short-term (6-week) placebo-controlled trials in which patients were dosed in a range of 20 to 50 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied ( TABLE 2):

TABLE 2A - Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials¹

TABLE 2B -

Obsessive Compulsive Disorder and Panic Disorder: Tables 3A and 3B enumerate adverse events that occurred at a frequency of 2% or more among OCD patients on paroxetine hydrochloride who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 to 60 mg/day or among patients with panic disorder on paroxetine hydrochloride who participated in placebo-controlled trials of 10 to 12 weeks duration in which patients were dosed in a range of 10 to 60 mg/day.

TABLE 3A - Treatment Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Obsessive Compulsive Disorder¹

TABLE 3B - Obsessive Compulsive Disorder

TABLE 3C - Treatment Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Panic Disorder¹

TABLE 3D - Panic Disorder

Dose Dependency of Adverse Events: A comparison of adverse event rates in a fixed-dose study comparing paroxetine hydrochloride 10, 20, 30 and 40 mg/day with placebo revealed a clear dose dependency for some of the more common adverse events associated with paroxetine hydrochloride use, as shown in the following table ( TABLE 4):

TABLE 4 - Treatment-Emergent Adverse Experience Incidence in a Dose-Comparison Trial*

In a fixed-dose study comparing placebo and paroxetine hydrochloride 20, 40 and 60 mg in the treatment of OCD, there was no clear relationship between adverse events and the dose of paroxetine hydrochloride to which patients were assigned. No new adverse events were observed in hte paroxetine hydrochloride 60 mg dose group compared to any of the other treatment groups.

In a fixed-dose study comparing placebo and paroxetine hydrochloride 10, 20 and 40 mg in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of paroxetine hydrochloride to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor and abnormal ejaculation. In flexible dose studies, no new adverse events were observed in patients receiving paroxetine hydrochloride 60 mg compared to any of the other treatment groups.

Adaptation to Certain Adverse Events: Over a 4- to 6-week period, there was evidence of adaptation to some adverse events with continued therapy (e.g., nausea and dizziness), but less to other effects (e.g., dry mouth, somnolence and asthenia).

Weight and Vital Sign Changes: Significant weight loss may be an undesirable result of treatment with paroxetine for some patients but, on average, patients in controlled trials had minimal (about 1 pound) weight loss vs. smaller changes on placebo and active control. No significant changes in vital signs (systolic and diastolic blood pressure, pulse and temperature) were observed in patients treated with paroxetine in controlled clinical trials.

ECG Changes: In an analysis of ECGs obtained in 682 patients treated with paroxetine and 415 patients treated with placebo in controlled clinical trials, no clinically significant changes were seen in the ECGs of either group.

Liver Function Tests: In placebo-controlled clinical trials, patients treated with paroxetine exhibited abnormal values on liver function tests at no greater rate than that seen in placebo-treated patients. In particular, the paroxetine-vs.-placebo comparison for alkaline phosphatase was 0% vs. 0%. SGOT 0.3% vs. 0.3%, SGPT 1% vs. 0.3% and bilirubin 0% vs. 0.8%.

Other Events Observed During the Premarketing Evaluation of Paroxetine Hydrochloride: During its premarketing assessment, multiple doses of paroxetine were administered to 4,126 patients in phase 2 and 3 studies. The conditions and duration of exposure to paroxetine varied greatly and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, and fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, reported adverse events were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 4,126 patients exposed to multiple doses of paroxetine hydrochloride who experienced an event of the type cited on at least one occasion while receiving paroxetine. All reported events are included except those already listed in TABLE 2, those reported in terms so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that although the events reported occurred during treatment with paroxetine, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Events of major clinical importance are also described in the PRECAUTIONS section.

Body as a Whole: frequent: chills, malaise; infrequent: allergic reaction, carcinoma, face edema, moniliasis, neck pain; rare: abscess, adrenergic syndrome, cellulitis, neck rigidity, pelvic pain, peritonitis, ulcer.

Cardiovascular System: frequent: hypertension, syncope, tachycardia; infrequent: bradycardia, conduction abnormalities, electrocardiogram abnormal, hypotension, migraine, peripheral vascular disorder; rare: angina pectoris, arrhythmia, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombosis, varicose vein, vascular headache, ventricular extrasystoles.

Digestive System: infrequent: bruxism, dysphagia, eructation, glossitis, increased salivation, liver function tests abnormal, mouth ulceration, rectal hemorrhage; rare: aphthous stomatitis, bloody diarrhea, bulimia, colitis, duodenitis, esophagitis, fecal impactions, fecal incontinence, gastritis, gastroenteritis, gingivitis, hematemesis, hepatitis, ileus, jaundice, melena, peptic ulcer, salivary gland enlargement, stomach ulcer, stomatitis, tongue edema, tooth caries.

Endocrine System: rare: diabetes mellitus, hyperthyroidism, hypothyroidism, thyroiditis.

Hemic and Lymphatic Systems: infrequent: anemia, leukopenia, lymphadenopathy, purpura; rare: abnormal erythrocytes, eosinophilia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia.

Metabolic and Nutritional: frequent: edema, weight gain, weight loss; infrequent: hyperglycemia, peripheral edema, thirst; rare: alkaline phosphatase increased, bilirubinemia, dehydration, gout, hypercholesteremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, SGOT increased, SGPT increased.

Musculoskeletal System: infrequent: arthralgia, arthritis; rare: arthrosis, bursitis, myositis, osteoporosis, tetany.

Nervous System: frequent: amnesia, CNS stimulation, concentration impaired, depression, emotional lability, vertigo; infrequent: abnormal thinking, akinesia, alcohol abuse, ataxia, convulsion, depersonalization, hallucinations, hyperkinesia, hypertonia, incoordination, lack of emotion, manic reaction, paranoid reaction; rare: abnormal electroencephalogram, abnormal gait, antisocial reaction, choreoathetosis, delirium, delusions, diplopia, drug dependence, dysarthria, dyskinesia, dystonia, euphoria, fasciculations, grand mal convulsion, hostility, hyperalgesia, hypokinesia, hysteria, libido increased, manic-depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, paralysis, psychosis, psychotic depression, reflexes increased, stupor, withdrawal syndrome.

Respiratory System: frequent: cough increased, rhinitis; infrequent: asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu, sinusitis; rare: carcinoma of lung, hiccups, lung fibrosis, sputum increased.

Skin and Appendages: frequent: pruritus; infrequent: acne, alopecia, dry skin, ecchymosis, eczema, furunculosis, urticaria; rare: angioedema, contact dermatitis, erythema nodosum, maculopapular rash, photosensitivity, skin discoloration, skin melanoma.

Special Senses: infrequent: abnormality of accommodation, ear pain, eye pain, mydriasis, otitis media, taste loss, tinnitus; rare: amblyopia, cataract, conjunctivitis, corneal ulcer, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, otitis externa, photophobia.

Urogenital System: infrequent: abortion, amenorrhea, breast pain, cystitis, dysmenorrhea, dysuria, menorrhagia, nocturia, polyuria, urethritis, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: breast atrophy, breast carcinoma, breast neoplasm, female lactation, hematuria, kidney calculus, kidney function abnormal, kidney pain, mastitis, nephritis, oliguria, prostatic carcinoma, vaginal moniliasis.

Postmarketing Reports: Voluntary reports of adverse events in patients taking paroxetine that have been received since market introduction and not listed above that may have no causal relationship with the drug include elevated liver function tests (the most severe case was a death due to liver necrosis, and one other case involved grossly elevated transaminases associated with severe liver dysfunction), toxic epidermal necrolysis, priapism, thrombocytopenia, syndrome of inappropriate ADH secretion, symptoms suggestive of prolactinemia and galactorrhea, neuroleptic malignant syndrome-like events; extrapyramidal symptoms which have included dystonia, akathisia, bradykinesia, cogwheel rigidity, hypertonia, oculogyric crisis which has been associated with concomitant use of pimozide, tremor and trismus; and serotonin syndrome, associated in some cases with concomitant use of serotonergic drugs and with drugs which may have impaired paroxetine metabolism (symptoms have included agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering, tachycardia and tremor). There have been spontaneous reports that abrupt discontinuation may lead to symptoms such as dizziness, sensory disturbances, agitation or anxiety, nausea and sweating; these events are generally self-limiting.

Drug Abuse and Dependence:

Controlled Substance Class: Paroxetine is not a controlled substance.

Physical and Psychologic Dependence: Paroxetine has not been systematically studied in animals or humans for its potential for abuse, tolerance or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted and/or abused once marketed. Consequently, patients should be evaluated carefully for history of drug abuse, and such patients should be observed closely for signs of paroxetine misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

Overdosage:

Human Experience: No deaths were reported following acute overdose with paroxetine alone or in combination with other drugs and/or alcohol (18 cases, with doses up to 850 mg) during premarketing clinical trials. Signs and symptoms of overdose with paroxetine included: nausea, vomiting, drowsiness, sinus tachycardia and dilated pupils. There were no reports of ECG abnormalities, coma or convulsions following overdosage with paroxetine alone.

Overdosage Management: Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. There are no specific antidotes for paroxetine. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Gastric evacuation either by the induction of emesis or lavage or both should be performed. In most cases, following evacuation, 20 to 30 grams of activated charcoal may be administered every 4 to 6 hours during the first 24 to 48 hours after ingestion. An ECG should be taken and monitoring of cardiac function instituted if there is any evidence of abnormality. Supportive care with frequent monitoring of vital signs and careful observation is indicated. Due to the large volume of distribution of paroxetine, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.

A specific caution involves patients taking or recently having taken paroxetine who might ingest by accident or intent excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and its active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation.

In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in Physicians GenR_X.

Dosage and Administration:

Depression

Depression Usual Initial Dosage: Paroxetine should be administered as a single daily dose, usually in the morning. The recommended initial dose is 20 mg/day. Patients were dosed in a range of 20 to 50 mg/day in the clinical trials demonstrating the antidepressant effectiveness of paroxetine hydrochloride. As with all antidepressants, the full antidepressant effect may be delayed. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.

Maintenance Therapy: There is no body of evidence available to answer the question of how long the patient treated with paroxetine hydrochloride should remain on it. It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy. Whether the dose of an antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder

Usual Initial Dosage: Paroxetine should be administered as a single daily dose, usually in the morning. The recommended dose of paroxetine hydrochloride in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week. Patients were dosed in a range of 20 to 60 mg/day in the clinical trials demonstrating the effectiveness of paroxetine hydrochloride in the treatment of OCD. The maximum dosage should not exceed 60 mg/day.

Maintenance Therapy: Long-term maintenance of efficacy was demonstrated in a 6-month relapse prevention trial. In this trial, patients with OCD assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY.) OCD is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder

Usual Initial Dosage: Paroxetine should be administered as a single daily dose, usually in the morning. The target dose of paroxetine hydrochloride in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/week increments and at intervals of at least 1 week. Patients were dosed in a range of 10 to 60 mg/day in the clinical trials demonstrating the effectiveness of paroxetine hydrochloride. The maximum dosage should not exceed 60 mg/day.

Maintenance Therapy: Long-term maintenance of efficacy was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY.) Panic disorder is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Switching Patients to or from a Monoamine Oxidase Inhibitor: At least 14 days should elapse between discontinuation of a MAOI and initiation of paroxetine hydrochloride therapy. Similarly, at least 14 days should be allowed after stopping paroxetine hydrochloride before starting an MAOI.

Patient Information:

Paroxetine HCl is used to treat depression, panic disorder and obsessive-compulsive disorders. Paroxetine HCl should not be taken if you are currently taking monoamine oxidase inhibitors. If you have been prescribed a monoamine oxidase inhibitor by another physician please call them for advice. Any drug which affects the central nervous system can cause drowsiness or lethargy. This drug has rarely been associated with this effect but caution is warranted while driving or operating machinery. Avoid drinking alcohol. Please consult with your physician or pharmacist whenever you are using another medication, especially over-the-counter medications since there may be interactions. Paroxetine is generally taken once a day, in the morning. It may take 4 or more weeks before improvement is symptoms is seen. You are encouraged to continue therapy until advised by your physician to stop.

How Supplied:

Paxil is supplied as film-coated, modified-oval tablets.

Storage: Store at controlled room temperature (15° to 30°C; 59° to 86°F).

How Supplied - Equivalents Not Available:

Tablet, Film-Coated - Oral - 10 mg

10 mg x 30

$56.80

Paxil, Beecham

00029-3210-13

Tablet, Film-Coated - Oral - 40 mg

40 mg x 30

$64.44

Paxil, Beecham

00029-3213-13

Tablet, Uncoated - Oral - 20 mg

100's	$189.90	Paxil, Beecham	00029-3211-20
100's	$193.80	Paxil, Beecham	00029-3211-21
30's	$57.00	Paxil, Beecham	00029-3211-13

Tablet, Uncoated - Oral - 30 mg

30's

$58.65

Paxil, Beecham

00029-3212-13

Copyright 1997 - Mosby Inc. - Mosby's GenRx