PAROXETINE- paroxetine hydrochloride hemihydrate_tablet, film coated

Pharmacodynamics: 1- 2- 2- 1- 2- 1 1- Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive. Pharmacokinetics: In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower C max Absorption and Distribution: 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 may take substantially longer in an occasional patient. At steady state, mean values of C max max min max min 0-24 The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the C max Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. 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 vitro protein binding of phenytoin or warfarin. Metabolism and Excretion: min 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 glucuronic 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 CYP2D6. 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 Drugs Metabolized by CYP2D6 Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound 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. Other Clinical Pharmacology Information: Specific Populations: Renal and Liver Disease: 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: min min DOSAGE AND ADMINISTRATION Drug-Drug Interactions: PRECAUTIONS: Drug Interactions Major Depressive Disorder: A study of outpatients with major depressive disorder who had responded to Paroxetine Tablets (HDRS total score <8) during an initial 8-week open-treatment phase and were then randomized to continuation on Paroxetine Tablets or placebo for 1 year demonstrated a significantly lower relapse rate for patients taking Paroxetine Tablets (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients. Obsessive Compulsive Disorder: The following table provides the outcome classification by treatment group on Global Improvement items of the Clinical Global Impression (CGI) scale for Study 1. Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 Outcome Placebo Paroxetine Tablets Paroxetine Tablets Paroxetine Tablets Worse 14% 7% 7% 3% No Change 44% 35% 22% 19% Minimally Improved 24% 33% 29% 34% Much Improved 11% 18% 22% 24% Very Much Improved 7% 7% 20% 20% 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 Paroxetine Tablets 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 mg/day 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: Study 1 was a 10-week dose-range finding study; patients were treated with fixed paroxetine doses of 10 mg/day, 20 mg/day, 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 mg 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 mg 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. Long-term maintenance effects of Paroxetine Tablets in panic disorder were demonstrated in an extension to Study 1. Patients who were responders during the 10-week double-blind phase and during a 3-month double-blind extension phase were randomized to either paroxetine (10 mg/day, 20 mg/day, or 40 mg/day) or placebo in a 3-month double-blind relapse prevention phase. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. Social Anxiety Disorder: Studies 1 and 2 were flexible-dose studies comparing paroxetine (20 mg to 50 mg daily) and placebo. Paroxetine demonstrated statistically significant superiority over placebo on both the CGI Improvement responder criterion and the Liebowitz Social Anxiety Scale (LSAS). In Study 1, for patients who completed to week 12, 69% of paroxetine-treated patients compared to 29% of placebo-treated patients were CGI Improvement responders. In Study 2, CGI Improvement responders were 77% and 42% for the paroxetine- and placebo-treated patients, respectively. Study 3 was a 12-week study comparing fixed paroxetine doses of 20 mg/day, 40 mg/day, or 60 mg/day with placebo. Paroxetine 20 mg was demonstrated to be significantly superior to placebo on both the LSAS Total Score and the CGI Improvement responder criterion; there were trends for superiority over placebo for the 40 mg/day and 60 mg/day dose groups. There was no indication in this study of any additional benefit for doses higher than 20 mg/day. Subgroup analyses generally did not indicate differences in treatment outcomes as a function of age, race, or gender. Generalized Anxiety Disorder: Study 1 was an 8-week study comparing fixed paroxetine doses of 20 mg/day or 40 mg/day with placebo. Doses of 20 mg or 40 mg of Paroxetine Tablets were both demonstrated to be significantly superior to placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score. There was not sufficient evidence in this study to suggest a greater benefit for the 40 mg/day dose compared to the 20 mg/day dose. Study 2 was a flexible-dose study comparing paroxetine (20 mg to 50 mg daily) and placebo. Paroxetine Tablets demonstrated statistically significant superiority over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score. A third study, also flexible-dose comparing paroxetine (20 mg to 50 mg daily), did not demonstrate statistically significant superiority of Paroxetine Tablets over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, the primary outcome. Subgroup analyses did not indicate differences in treatment outcomes as a function of race or gender. There were insufficient elderly patients to conduct subgroup analyses on the basis of age. In a longer-term trial, 566 patients meeting DSM-IV criteria for Generalized Anxiety Disorder, who had responded during a single-blind, 8-week acute treatment phase with 20 mg/day to 50 mg/day of Paroxetine Tablets, were randomized to continuation of Paroxetine Tablets at their same dose, or to placebo, for up to 24 weeks of observation for relapse. Response during the single-blind phase was defined by having a decrease of >=2 points compared to baseline on the CGI-Severity of Illness scale, to a score of <=3. Relapse during the double-blind phase was defined as an increase of >=2 points compared to baseline on the CGI-Severity of Illness scale to a score of >=4, or withdrawal due to lack of efficacy. Patients receiving continued Paroxetine Tablets experienced a significantly lower relapse rate over the subsequent 24 weeks compared to those receiving placebo.

Major Depressive Disorder: The efficacy of Paroxetine Tablets 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: Clinical Trials The effects of Paroxetine Tablets in hospitalized depressed patients have not been adequately studied. The efficacy of Paroxetine Tablets in maintaining a response in major depressive disorder for up to 1 year was demonstrated in a placebo-controlled trial (see CLINICAL PHARMACOLOGY: Clinical Trials Obsessive Compulsive Disorder: The efficacy of Paroxetine Tablets was established in two 12-week trials with obsessive compulsive outpatients whose diagnoses corresponded most closely to the DSM-IIIR category of obsessive compulsive disorder (see CLINICAL PHARMACOLOGY: Clinical Trials Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses, or images (obsessions) that are ego-dystonic 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: Clinical Trials DOSAGE AND ADMINISTRATION Panic Disorder: The efficacy of Paroxetine Tablets 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 PHARMACOLOGY: Clinical Trials Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, i. , a discrete period of intense fear or discomfort in which 4 (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart, or accelerated heart rate; (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 flushes. 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: Clinical Trials DOSAGE AND ADMINISTRATION Social Anxiety Disorder: The efficacy of Paroxetine Tablets was established in three 12-week trials in adult patients with social anxiety disorder (DSM-IV). Paroxetine Tablets have not been studied in children or adolescents with social phobia (see CLINICAL PHARMACOLOGY: Clinical Trials The effectiveness of Paroxetine Tablets in long-term treatment of social anxiety disorder, i. , for more than 12 weeks, has not been systematically evaluated in adequate and well-controlled trials. Therefore, the physician who elects to prescribe Paroxetine Tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION Generalized Anxiety Disorder: The efficacy of Paroxetine Tablets in the treatment of GAD was established in two 8-week placebo-controlled trials in adults with GAD. Paroxetine Tablets have not been studied in children or adolescents with Generalized Anxiety Disorder (see CLINICAL PHARMACOLOGY: Clinical Trials Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least 3 of the following 6 symptoms: Restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, sleep disturbance. The efficacy of Paroxetine Tablets in maintaining a response in patients with Generalized Anxiety Disorder, who responded during an 8-week acute treatment phase while taking Paroxetine Tablets and were then observed for relapse during a period of up to 24 weeks, was demonstrated in a placebo-controlled trial (see CLINICAL PHARMACOLOGY: Clinical Trials DOSAGE AND ADMINISTRATION.

Major Depressive Disorder: Usual Initial Dosage: Maintenance Therapy: Systematic evaluation of the efficacy of Paroxetine Tablets 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: Maintenance Therapy: CLINICAL PHARMACOLOGY: Clinical Trials Panic Disorder: Usual Initial Dosage: Maintenance Therapy: CLINICAL PHARMACOLOGY: Clinical Trials Social Anxiety Disorder: Usual Initial Dosage: CLINICAL PHARMACOLOGY: Clinical Trials Maintenance Therapy: Generalized Anxiety Disorder: Usual Initial Dosage: Maintenance Therapy: CLINICAL PHARMACOLOGY: Clinical Trials Special Populations: Treatment of Pregnant Women During the Third Trimester: WARNINGS Usage in Pregnancy Dosage for Elderly or Debilitated Patients, and Patients With Severe Renal or Hepatic Impairment: Switching a Patient to or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders: CONTRAINDICATIONS Use of Paroxetine Tablets With Other MAOIs Such as Linezolid or Methylene Blue: CONTRAINDICATIONS In some cases, a patient already receiving therapy with Paroxetine Tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, Paroxetine Tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Paroxetine Tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with Paroxetine Tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS Discontinuation of Treatment With Paroxetine Tablets: PRECAUTIONS Discontinuation of Treatment With Paroxetine Tablets.

Associated With Discontinuation of Treatment: Major OCD Panic Social Anxiety Generalized Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo CNS Somnolence 2. 2% Insomnia - - 1. 1% 0% Agitation 1. 5% - Tremor 1. 7% 0% Anxiety - - - 1. 1% 0% Dizziness - - 1. 2% Gastrointestinal Constipation - 1. 1% 0% Nausea 3. 2% Diarrhea 1. 3% - Dry mouth 1. 3% - Vomiting 1. 0% 0% Flatulence 1. 3% Other Asthenia 1. 2% Abnormal ejaculation Incidence corrected for gender. 5% Sweating 1. 2% Impotence - 1. 5% 0% Libido Decreased 1. 0% 0% Where numbers are not provided the incidence of the adverse events in patients treated with Paroxetine Tablets was not >1% or was not greater than or equal to 2 times the incidence of placebo. Commonly Observed Adverse Events: Major Depressive Disorder: Table 2 Obsessive Compulsive Disorder: Table 3 Panic Disorder: Table 3 Social Anxiety Disorder: Table 3 Generalized Anxiety Disorder: Table 4 Incidence in Controlled Clinical Trials: Major Depressive Disorder: Table 2. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Major Depressive Disorder Events reported by at least 1% of patients treated with Paroxetine Tablets are included, except the following events which had an incidence on placebo >= Paroxetine Tablets: Abdominal pain, agitation, back pain, chest pain, CNS stimulation, fever, increased appetite, myoclonus, pharyngitis, postural hypotension, respiratory disorder (includes mostly “cold symptoms” or “URI”), trauma, and vomiting. Body System Preferred Term Paroxetine Tablets Placebo ( n = 421 ) ( n = 421 ) Body as a Whole Headache 18% 17% Asthenia 15% 6% Cardiovascular Palpitation 3% 1% Vasodilation 3% 1% Dermatologic Sweating 11% 2% Rash 2% 1% Gastrointestinal Nausea 26% 9% Dry Mouth 18% 12% Constipation 14% 9% Diarrhea 12% 8% Decreased Appetite 6% 2% Flatulence 4% 2% Oropharynx Disorder Includes mostly “lump in throat” and “tightness in throat. ” 2% 0% Dyspepsia 2% 1% Musculoskeletal Myopathy 2% 1% Myalgia 2% 1% Myasthenia 1% 0% Nervous System Somnolence 23% 9% Dizziness 13% 6% Insomnia 13% 6% Tremor 8% 2% Nervousness 5% 3% Anxiety 5% 3% Paresthesia 4% 2% Libido Decreased 3% 0% Drugged Feeling 2% 1% Confusion 1% 0% Respiration Yawn 4% 0% Special Senses Blurred Vision 4% 1% Taste Perversion 2% 0% Urogenital System Ejaculatory Disturbance Percentage corrected for gender. , Mostly “ejaculatory delay. ” 13% 0% Other Male Genital Disorders , Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction,” and “impotence. ” 10% 0% Urinary Frequency 3% 1% Urination Disorder Includes mostly “difficulty with micturition” and “urinary hesitancy. ” 3% 0% Female Genital Disorders , Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm. ” 2% 0% Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Table 3. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder Events reported by at least 2% of OCD, panic disorder, and social anxiety disorder in patients treated with Paroxetine Tablets are included, except the following events which had an incidence on placebo >= Paroxetine Tablets: [OCD]: Abdominal pain, agitation, anxiety, back pain, cough increased, depression, headache, hyperkinesia, infection, paresthesia, pharyngitis, respiratory disorder, rhinitis, and sinusitis. [panic disorder]: Abnormal dreams, abnormal vision, chest pain, cough increased, depersonalization, depression, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, myalgia, nervousness, palpitation, paresthesia, pharyngitis, rash, respiratory disorder, sinusitis, taste perversion, trauma, urination impaired, and vasodilation. [social anxiety disorder]: Abdominal pain, depression, headache, infection, respiratory disorder, and sinusitis. Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder Body System Preferred Term Paroxetine Tablets Placebo Paroxetine Tablets Placebo Paroxetine Tablets Placebo Body as a Whole Asthenia 22% 14% 14% 5% 22% 14% Abdominal Pain em dash em dash 4% 3% em dash em dash Chest Pain 3% 2% em dash em dash em dash em dash Back Pain em dash em dash 3% 2% em dash em dash Chills 2% 1% 2% 1% em dash em dash Trauma em dash em dash em dash em dash 3% 1% Cardiovascular Vasodilation 4% 1% em dash em dash em dash em dash Palpitation 2% 0% em dash em dash em dash em dash Dermatologic Sweating 9% 3% 14% 6% 9% 2% Rash 3% 2% em dash em dash em dash em dash Gastrointestinal Nausea 23% 10% 23% 17% 25% 7% Dry Mouth 18% 9% 18% 11% 9% 3% Constipation 16% 6% 8% 5% 5% 2% Diarrhea 10% 10% 12% 7% 9% 6% Decreased Appetite 9% 3% 7% 3% 8% 2% Dyspepsia em dash em dash em dash em dash 4% 2% Flatulence em dash em dash em dash em dash 4% 2% Increased Appetite 4% 3% 2% 1% em dash em dash Vomiting em dash em dash em dash em dash 2% 1% Musculoskeletal Myalgia em dash em dash em dash em dash 4% 3% Nervous System Insomnia 24% 13% 18% 10% 21% 16% Somnolence 24% 7% 19% 11% 22% 5% Dizziness 12% 6% 14% 10% 11% 7% Tremor 11% 1% 9% 1% 9% 1% Nervousness 9% 8% em dash em dash 8% 7% Libido Decreased 7% 4% 9% 1% 12% 1% Agitation em dash em dash 5% 4% 3% 1% Anxiety em dash em dash 5% 4% 5% 4% Abnormal Dreams 4% 1% em dash em dash em dash em dash Concentration Impaired 3% 2% em dash em dash 4% 1% Depersonalization 3% 0% em dash em dash em dash em dash Myoclonus 3% 0% 3% 2% 2% 1% Amnesia 2% 1% em dash em dash em dash em dash Respiratory System Rhinitis em dash em dash 3% 0% em dash em dash Pharyngitis em dash em dash em dash em dash 4% 2% Yawn em dash em dash em dash em dash 5% 1% Special Senses Abnormal Vision 4% 2% em dash em dash 4% 1% Taste Perversion 2% 0% em dash em dash em dash em dash Urogenital System Abnormal Ejaculation Percentage corrected for gender. 23% 1% 21% 1% 28% 1% Dysmenorrhea em dash em dash em dash em dash 5% 4% Female Genital Disorder 3% 0% 9% 1% 9% 1% Impotence 8% 1% 5% 0% 5% 1% Urinary Frequency 3% 1% 2% 0% em dash em dash Urination Impaired 3% 0% em dash em dash em dash em dash Urinary Tract Infection 2% 1% 2% 1% em dash em dash Generalized Anxiety Disorder: Table 4. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Generalized Anxiety Events reported by at least 2% of GAD in patients treated with Paroxetine Tablets are included, except the following events which had an incidence on placebo >= Paroxetine Tablets [GAD]: Abdominal pain, back pain, trauma, dyspepsia, myalgia, and pharyngitis. Generalized Anxiety Disorder Body System Preferred Term Paroxetine Placebo Body as a Whole Asthenia 14% 6% Headache 17% 14% Infection 6% 3% Abdominal Pain Trauma Cardiovascular Vasodilation 3% 1% Dermatologic Sweating 6% 2% Gastrointestinal Nausea 20% 5% Dry Mouth 11% 5% Constipation 10% 2% Diarrhea 9% 7% Decreased Appetite 5% 1% Vomiting 3% 2% Dyspepsia em dash em dash Nervous System Insomnia 11% 8% Somnolence 15% 5% Dizziness 6% 5% Tremor 5% 1% Nervousness 4% 3% Libido Decreased 9% 2% Abnormal Dreams Respiratory System Respiratory Disorder 7% 5% Sinusitis 4% 3% Yawn 4% em dash Special Senses Abnormal Vision 2% 1% Urogenital System Abnormal Ejaculation Percentage corrected for gender. 25% 2% Female Genital Disorder 4% 1% Impotence 4% 3% Adaptation to Certain Adverse Events: Male and Female Sexual Dysfunction With SSRIs: Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the reported incidence of sexual side effects in males and females with major depressive disorder, OCD, panic disorder, social anxiety disorder and GAD are displayed in Table 6. Incidence of Sexual Adverse Events in Controlled Clinical Trials Paroxetine Tablets Placebo n (males) 1446 1042 Decreased Libido 6-15% 0-5% Ejaculatory Disturbance 13-28% 0-2% Impotence 2-9% 0-3% n (females) 1822 1340 Decreased Libido 0-9% 0-2% Orgasmic Disturbance 2-9% 0-1% There are no adequate and well-controlled studies examining sexual dysfunction with paroxetine treatment. Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects. Weight and Vital Sign Changes: ECG Changes: Liver Function Tests: Hallucinations: Other Events Observed During the Premarketing Evaluation of Paroxetine Tablets: 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 9,089 patients exposed to multiple doses of Paroxetine Tablets who experienced an event of the type cited on at least 1 occasion while receiving Paroxetine Tablets. All reported events are included except those already listed in Tables 2 to 5, 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 1 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 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are also described in the PRECAUTIONS Body as a Whole: Infrequent: rare: Cardiovascular System: Frequent: infrequent: rare: Digestive System: Infrequent: rare: Endocrine System: Rare: Hemic and Lymphatic Systems: Infrequent: rare: Metabolic and Nutritional: Frequent: infrequent: rare: Musculoskeletal System: Frequent: infrequent: rare: Nervous System: Frequent: infrequent: rare: Respiratory System: Infrequent: rare: Skin and Appendages: Frequent: infrequent: rare: Special Senses: Frequent: infrequent: rare: Urogenital System: Infrequent: rare: Postmarketing Reports:.

The use of MAOIs intended to treat psychiatric disorders with Paroxetine Tablets or within 14 days of stopping treatment with Paroxetine Tablets is contraindicated because of an increased risk of serotonin syndrome. The use of Paroxetine Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS DOSAGE AND ADMINISTRATION Starting Paroxetine Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS DOSAGE AND ADMINISTRATION Concomitant use with thioridazine is contraindicated (see WARNINGS PRECAUTIONS Concomitant use in patients taking pimozide is contraindicated (see PRECAUTIONS Paroxetine Tablets are contraindicated in patients with a hypersensitivity to paroxetine or any of the inactive ingredients in Paroxetine Tablets.

WARNINGS
Clinical Worsening and Suicide Risk: The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1. Table 1 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18-24 5 additional cases Decreases Compared to Placebo 25-64 1 fewer case >=65 6 fewer cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i. , beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient''s presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS DOSAGE AND ADMINISTRATION Discontinuation of Treatment With Paroxetine Tablets Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Screening Patients for Bipolar Disorder: Serotonin Syndrome: Serotonin syndrome symptoms may include mental status changes (e. , agitation, hallucinations, delirium and coma), autonomic instability (e. , tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e. , tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e. , nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. The concomitant use of Paroxetine Tablets with MAOIs intended to treat psychiatric disorders is contraindicated. Paroxetine Tablets should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Paroxetine Tablets. Paroxetine Tablets should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS DOSAGE AND ADMINISTRATION If concomitant use of Paroxetine Tablets with certain other serotonergic drugs, i. , triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. Treatment with Paroxetine Tablets and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Angle-Closure Glaucoma: Potential Interaction With Thioridazine: Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointesen dashtype arrhythmias, and sudden death. This effect appears to be dose related. An in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS PRECAUTIONS Usage in Pregnancy: Teratogenic Effects: A study based on Swedish national registry data demonstrated that infants exposed to paroxetine during pregnancy (n = 815) had an increased risk of cardiovascular malformations (2% risk in paroxetine-exposed infants) compared to the entire registry population (1% risk), for an odds ratio (OR) of 1. 8 (95% confidence interval 1. No increase in the risk of overall congenital malformations was seen in the paroxetine-exposed infants. The cardiac malformations in the paroxetine-exposed infants were primarily ventricular septal defects (VSDs) and atrial septal defects (ASDs). Septal defects range in severity from those that resolve spontaneously to those which require surgery. A separate retrospective cohort study from the United States (United Healthcare data) evaluated 5,956 infants of mothers dispensed antidepressants during the first trimester (n = 815 for paroxetine). This study showed a trend towards an increased risk for cardiovascular malformations for paroxetine (risk of 1. 5%) compared to other antidepressants (risk of 1%), for an OR of 1. 5 (95% confidence interval 0. Of the 12 paroxetine-exposed infants with cardiovascular malformations, 9 had VSDs. This study also suggested an increased risk of overall major congenital malformations including cardiovascular defects for paroxetine (4% risk) compared to other (2% risk) antidepressants (OR 1. 8; 95% confidence interval 1. Two large case-control studies using separate databases, each with >9,000 birth defect cases and >4,000 controls, found that maternal use of paroxetine during the first trimester of pregnancy was associated with a 2- to 3-fold increased risk of right ventricular outflow tract obstructions. In one study the odds ratio was 2. 5 (95% confidence interval, 1. 0, 7 exposed infants) and in the other study the odds ratio was 3. 3 (95% confidence interval, 1. 8, 6 exposed infants). Other studies have found varying results as to whether there was an increased risk of overall, cardiovascular, or specific congenital malformations. A meta-analysis of epidemiological data over a 16-year period (1992 to 2008) on first trimester paroxetine use in pregnancy and congenital malformations included the above-noted studies in addition to others (n = 17 studies that included overall malformations and n = 14 studies that included cardiovascular malformations; n = 20 distinct studies). While subject to limitations, this meta-analysis suggested an increased occurrence of cardiovascular malformations (prevalence odds ratio [POR] 1. 5; 95% confidence interval 1. 9) and overall malformations (POR 1. 2; 95% confidence interval 1. 4) with paroxetine use during the first trimester. It was not possible in this meta-analysis to determine the extent to which the observed prevalence of cardiovascular malformations might have contributed to that of overall malformations, nor was it possible to determine whether any specific types of cardiovascular malformations might have contributed to the observed prevalence of all cardiovascular malformations. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant (see PRECAUTIONS: Discontinuation of Treatment With Paroxetine Tablets). Animal Findings: 2 2 Nonteratogenic Effects: WARNINGS Serotonin Syndrome Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 en dash 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including Paroxetine Tablets) in pregnancy and PPHN. Other studies do not show a significant statistical association. Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy. When treating a pregnant woman with Paroxetine Tablets, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis (see DOSAGE AND ADMINISTRATION ADVERSE REACTIONS: Postmarketing Reports.
OVERDOSAGE
Human Experience: Commonly reported adverse events associated with paroxetine overdosage include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including torsade de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention. Overdosage Management: Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be of benefit. A specific caution involves patients who are taking or have recently taken paroxetine who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation (see PRECAUTIONS Drugs Metabolized by Cytochrome CYP2D6 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 the Physicians’ Desk Reference.
Medication Guide
Paroxetine Tablets USP Read the Medication Guide that comes with Paroxetine Tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about Paroxetine Tablets? Paroxetine Tablets and other antidepressant medicines may cause serious side effects, including: 1. Suicidal thoughts or actions: Paroxetine Tablets and other antidepressant medicines may increase suicidal thoughts or actions first few months of treatment or when the dose is changed Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when Paroxetine Tablets are started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violent thoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry, or irritable trouble sleeping an increase in activity or talking more than what is normal for you other unusual changes in behavior or mood Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Paroxetine Tablets may be associated with these serious side effects: 2. Serotonin Syndrome or Neuroleptic Malignant Syndrome-like reactions. This condition can be life-threatening and may include: agitation, hallucinations, coma, or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity 3. Visual problems eye pain changes in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. 4. Severe allergic reactions: trouble breathing swelling of the face, tongue, eyes, or mouth rash, itchy welts (hives), or blisters, alone or with fever or joint pain 5. Abnormal bleeding: "registered" "registered" 6. Seizures or convulsions 7. Manic episodes: greatly increased energy severe trouble sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual 8. Changes in appetite or weight. 9. Low salt (sodium) levels in the blood. headache weakness or feeling unsteady confusion, problems concentrating or thinking, or memory problems Do not stop Paroxetine Tablets without first talking to your healthcare provider. anxiety, irritability, high or low mood, feeling restless, or changes in sleep habits headache, sweating, nausea, dizziness electric shock-like sensations, shaking, confusion What are Paroxetine Tablets? Paroxetine Tablets are prescription medicines used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Paroxetine Tablets are also used to treat: Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder Social Anxiety Disorder Generalized Anxiety Disorder (GAD) Talk to your healthcare provider if you do not think that your condition is getting better with treatment using Paroxetine Tablets. Who should not take Paroxetine Tablets? Do not take Paroxetine Tablets if you: are allergic to paroxetine or any of the ingredients in Paroxetine Tablets. See the end of this Medication Guide for a complete list of ingredients in Paroxetine Tablets. take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping Paroxetine Tablets unless directed to do so by your physician. Do not start Paroxetine Tablets if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. People who take Paroxetine Tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever uncontrolled muscle spasms stiff muscles rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out) take MELLARIL registered* (thioridazine). Do not take MELLARIL registered* together with Paroxetine Tablets because this can cause serious heart rhythm problems or sudden death. take the antipsychotic medicine pimozide (ORAP registered* ) because this can cause serious heart problems. What should I tell my healthcare provider before taking Paroxetine Tablets? Ask if you are not sure. Before starting Paroxetine Tablets, tell your healthcare provider if you: are pregnant, may be pregnant, or plan to become pregnant are breastfeeding. are taking certain drugs such as: triptans used to treat migraine headache other antidepressants (SSRIs, SNRIs, tricyclics, or lithium) or antipsychotics drugs that affect serotonin, such as lithium, tramadol, tryptophan, St. John’s wort certain drugs used to treat irregular heart beats certain drugs used to treat schizophrenia certain drugs used to treat HIV infection certain drugs that affect the blood, such as warfarin, aspirin, and ibuprofen certain drugs used to treat epilepsy atomoxetine cimetidine fentanyl metoprolol pimozide procyclidine tamoxifen have liver problems have kidney problems have heart problems have or had seizures or convulsions have bipolar disorder or mania have low sodium levels in your blood have a history of a stroke have high blood pressure have or had bleeding problems have glaucoma (high pressure in the eye) Tell your healthcare provider about all the medicines you take Your healthcare provider or pharmacist can tell you if it is safe to take Paroxetine Tablets with your other medicines. Do not start or stop any medicine while taking Paroxetine Tablets without talking to your healthcare provider first. If you take Paroxetine Tablets, you should not take any other medicines that contain paroxetine, including paroxetine extended-release tablets and PEXEVA registered* How should I take Paroxetine Tablets? Take Paroxetine Tablets exactly as prescribed. Your healthcare provider may need to change the dose of Paroxetine Tablets until it is the right dose for you. Paroxetine Tablets may be taken with or without food. If you miss a dose of Paroxetine Tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Paroxetine Tablets at the same time. If you take too many Paroxetine Tablets call your healthcare provider or poison control center right away, or get emergency treatment. Do not stop taking Paroxetine Tablets suddenly without talking to your doctor (unless you have symptoms of a severe allergic reaction). If you need to stop taking Paroxetine Tablets, your healthcare provider can tell you how to safely stop taking it. What should I avoid while taking Paroxetine Tablets? Paroxetine Tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Paroxetine Tablets affect you. Do not drink alcohol while using Paroxetine Tablets. What are possible side effects of Paroxetine Tablets? Paroxetine Tablets may cause serious side effects, including all of those described in the section entitled “What is the most important information I should know about Paroxetine Tablets?” Common possible side effects in people who take Paroxetine Tablets include: nausea sleepiness weakness dizziness feeling anxious or trouble sleeping sexual problems sweating shaking not feeling hungry dry mouth constipation infection yawning Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Paroxetine Tablets. For more information, ask your healthcare provider or pharmacist. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO SOLCO HEALTHCARE US, LLC AT 1-866-257-2597 OR TO THE FDA AT 1-800-FDA1088 or 1-800-332-1088. How should I store Paroxetine Tablets? Store Paroxetine Tablets at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Keep Paroxetine Tablets away from light. Keep bottle of Paroxetine Tablets closed tightly. Keep Paroxetine Tablets and all medicines out of the reach of children. General information about Paroxetine Tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Paroxetine Tablets for a condition for which it was not prescribed. Do not give Paroxetine Tablets to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about Paroxetine Tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Paroxetine Tablets that is written for healthcare professionals. What are the ingredients in Paroxetine Tablets? Active ingredient: Inactive ingredients in tablets: *: Brand names listed are trademarks of their respective owners and are not trademarks of Solco Healthcare US, LLC. This Medication Guide has been approved by the U.S. Food and Drug Administration.

Lake Erie Medical DBA Quality Care Products LLC

PAROXETINE- paroxetine hydrochloride hemihydrate_tablet, film coated Product manual source documgent