PAROXETINE- paroxetine hydrochloride hemihydrate_tablet, film coated

The mechanism of action of paroxetine tablets in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but 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 (SSRI) and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Nonlinearity in pharmacokinetics is observed with increasing doses of paroxetine tablets. 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 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 ½ max min 0-24 Effect of Food 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 Distribution 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 Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine tablets. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg 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 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 Drug Interactions ( 7 Excretion 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. Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions ( 7 Figure 1. Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2. Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Drugs Metabolized by Cytochrome CYP3A4 An in vivo in vitro Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. The recommended starting dosage and maximum dosage of paroxetine tablets is reduced in elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment [see Dosage and Administration ( 2. Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) FIGURE FIGURE2 FIGURE 3.

Paroxetine tablets are indicated in adults for the treatment of: Major depressive disorder (MDD) Obsessive compulsive disorder (OCD) Panic disorder (PD) Social anxiety disorder (SAD) Generalized anxiety disorder (GAD) Posttraumatic stress disorder (PTSD) Paroxetine tablets are a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of ( 1 Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD).

Recommended starting and maximum daily dosage for MDD, OCD, PD, and PTSD: ( 2. 2 Indication Starting Daily Dose Maximum Daily Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg Recommended starting dosage for SAD and GAD is 20 mg daily. 3 Elderly patients, patients with severe renal impairment or severe hepatic impairment: Starting dosage is 10 mg daily. Maximum dosage is 40 mg daily. 4 When discontinuing paroxetine tablets, reduce dosage gradually. 7 Administer paroxetine tablets as a single daily dose in the morning, with or without food. The recommended starting dosages and maximum dosages of paroxetine tablets in patients with MDD, OCD, PD, and PTSD are presented in Table 1. In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. Table 1: Recommended Daily Dosage of Paroxetine Tablets in Patients with MDD, OCD, PD, and PTSD Indication Starting Dose Maximum Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg SAD The starting and recommended dosage in patients with SAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets was demonstrated in patients dosed in a range of 20 mg to 60 mg daily. While the safety of paroxetine tablets has been evaluated in patients with SAD at doses up to 60 mg daily, available information does not suggest any additional benefit for doses above 20 mg daily [see Clinical Studies ( 14. 4 GAD The starting and recommended dosage in patients with GAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets in GAD was demonstrated in patients dosed in a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg daily [see Clinical Studies ( 14. 5 In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. Prior to initiating treatment with paroxetine tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5. 6 The recommended initial dosage is 10 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Dosage should not exceed 40 mg/day. At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI and initiation of paroxetine tablets. In addition, at least 14 days must elapse after stopping paroxetine tablets before starting an MAOI antidepressant [see Contraindications ( 4 5. 2 Adverse reactions may occur upon discontinuation of paroxetine tablets [see Warnings and Precautions ( 5.

The following adverse reactions are included in more detail in other sections of the prescribing information: Hypersensitivity reactions to paroxetine [see Contraindications ( 4 Suicidal Thoughts and Behaviors [see Warnings and Precautions ( 5. 1 Serotonin Syndrome [see Warnings and Precautions ( 5. 2 Embryofetal Toxicity [see Warnings and Precautions ( 5. 4 Increased Risk of Bleeding [see Warnings and Precautions ( 5. 5 )] Activation of Mania/Hypomania [see Warnings and Precautions ( 5. 6 Discontinuation Syndrome [see Warnings and Precautions ( 5. 7 Seizures [see Warnings and Precautions ( 5. 8 Angle-closure Glaucoma [see Warnings and Precautions ( 5. 9 Hyponatremia [see Warnings and Precautions ( 5. 10 Bone Fracture [see Warnings and Precautions ( 5. 12 Sexual Dysfunction [see Warnings and Precautions ( 5. 13 Most common adverse reactions (>=5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn. ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC. at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data for paroxetine tablets are from: 6-week clinical trials in MDD patients who received paroxetine tablets 20 mg to 50 mg once daily 12-week clinical trials in OCD patients who received paroxetine tablets 20 mg to 60 mg once daily 10- to 12-week clinical trials in PD patients who received paroxetine tablets 10 mg to 60 mg once daily 12-week clinical trials in SAD patients who received paroxetine tablets 20 mg to 50 mg once daily 8-week clinical trials in GAD patients who received paroxetine tablets 10 mg to 50 mg once daily 12-week clinical trials in PTSD patients who received paroxetine tablets 20 mg to 50 mg once daily Adverse Reactions Leading to Discontinuation Twenty percent (1,199/6,145) of patients treated with paroxetine tablets in clinical trials in MDD and 16. 1% (84/522), 11. 8% (64/542), 9. 4% (44/469), 10. 7% (79/735), and 11. 7% (79/676) of patients treated with paroxetine tablets in clinical trials in SAD, OCD, PD, GAD, and PTSD, respectively, discontinued treatment due to an adverse reaction. The most common adverse reactions (>=1%) associated with discontinuation (i. , those adverse reactions associated with dropout at a rate approximately twice or greater for paroxetine tablets compared to placebo) are presented in Table 3: Table 3: Adverse Reactions Reported as Leading to Discontinuation (>=1% of Paroxetine Tablets-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials MDD OCD PD SAD GAD PTSD Paroxetine Tablets % Placebo % Paroxetine Tablets % Placebo % Paroxetine Tablets % Placebo % Paroxetine Tablets % Placebo % Paroxetine Tablets % Placebo % Paroxetine Tablets % Placebo % CNS Somnolence 2. 7 em dash 1. 6 Insomnia em dash em dash 1. 1 0 em dash em dash Agitation 1. 5 em dash em dash em dash Tremor 1. 3 em dash 1. 2 Anxiety em dash em dash em dash 1. 1 0 em dash em dash Dizziness em dash em dash 1. 2 em dash em dash Gastroin- testinal Constipation em dash 1. 1 0 em dash em dash Nausea 3. 6 Diarrhea 1. 3 em dash Dry mouth 1. 3 em dash em dash em dash Vomiting 1. 0 0 em dash em dash Flatulence 1. 3 em dash em dash Other Asthenia 1. 2 Abnormal Ejaculation a 1. 5 em dash em dash Sweating 1. 2 em dash em dash Impotence a em dash 1. 5 0 em dash em dash Libido Decreased 1. 0 0 em dash em dash Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine tablets was not >1% or was not greater than or equal to 2 times the incidence of placebo. Most Common Adverse Reactions The most commonly observed adverse reactions associated with the use of paroxetine tablets (incidence of 5% or greater and at least twice that for placebo) were: MDD: OCD PD: SAD: GAD: PTSD: Adverse Reactions in Patients with MDD Table 4 presents the adverse reactions that occurred at an incidence of 1% or more and greater than placebo in clinical trials of paroxetine tablets -treated patients with MDD. Table 4: Adverse Reactions (>=1% of Paroxetine Tablets-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD Body System/ Adverse Reaction Paroxetine Tablets (n = 421) % Placebo (n = 421) % Body as a Whole Headache Asthenia 18 15 17 6 Cardiovascular 3 3 1 1 Dermatologic Sweating Rash 11 2 2 1 Gastrointestinal Nausea Dry Mouth Constipation Diarrhea Decreased Appetite Flatulence Oropharynx Disorder a Dyspepsia 26 18 14 12 6 4 2 2 9 12 9 8 2 2 0 1 Musculoskeletal Myasthenia 2 2 1 1 1 0 Nervous System Libido Decreased Drugged Feeling Confusion 23 13 13 8 5 5 4 3 2 1 9 6 6 2 3 3 2 0 1 0 Respiration Yawn 4 0 Special Senses Blurred Vision 4 1 Taste Perversion 2 0 Urogenital System Ejaculatory Disturbance b,c 13 0 Other Male Genital Disorders b,d 10 0 Urinary Frequency 3 1 Urination Disorder e 3 0 Female Genital Disorders b,f 2 0 Includes mostly “lump in throat” and “tightness in throat. ” Percentage corrected for gender. Mostly “ejaculatory delay. ” Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction,” and “impotence. ” Includes mostly “difficulty with micturition” and “urinary hesitancy. ” Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm. ” Adverse Reactions in Patients with OCD, PD, and SAD Table 5 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD, PD, and SAD. Adverse Reactions (>=2% of Paroxetine Tablets Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD Body System/Preferred Term Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder Paroxetine Tablets (n = 542) % Placebo (n = 265) % Paroxetine Tablets (n = 469) % Placebo (n = 324) % Paroxetine Tablets (n = 425) % Placebo (n = 339) % Body as a Whole Asthenia 22 14 14 5 22 14 Abdominal Pain - - 4 3 em dash em dash Chest Pain 3 2 - - - - Back Pain - - 3 2 - - 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 - - - - 4 2 Flatulence - - - - 4 2 Increased Appetite 4 3 2 1 - - Vomiting - - - - 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 - - - - Respiratory System - em dash - - em dash - 3 em dash - 0 em dash - Rhinitis - - Pharyngitis 4 2 Yawn 5 1 Special Senses Abnormal Vision 4 2 em dash em dash 4 1 Taste Perversion 2 0 - - - - Urogenital System Abnormal Ejaculation a 23 1 21 1 28 1 Dysmenorrhea em dash em dash em dash em dash 5 4 Female Genital Disorder a 3 0 9 1 9 1 Impotence a 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 Percentage corrected for gender. Adverse Reactions in Patients with GAD and PTSD Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD. Adverse Reactions (>=2% of Paroxetine Tablets-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD a Body System/Preferred Term Generalized Anxiety Disorder Posttraumatic Stress Disorder Paroxetine Tables (n = 735) % Placebo (n = 529) % Paroxetine Tables (n = 676) % Placebo (n = 504) % Body as a Whole Asthenia Headache Infection Abdominal Pain Trauma 14 17 6 6 14 3 12 --- 5 4 6 4 --- 4 3 5 Cardiovascular Vasodilation 3 1 2 1 Dermatologic Sweating 6 2 5 1 Gastrointestinal Nausea Dry Mouth Constipation Diarrhea Decreased Appetite Vomiting Dyspepsia 20 11 10 9 5 3 --- 5 5 2 7 1 2 --- 19 10 5 11 6 3 5 8 5 3 5 3 2 3 Nervous System Insomnia Somnolence Dizziness Tremor Nervousness Libido Decreased Abnormal Dreams 11 15 6 5 4 9 8 5 5 1 3 2 12 16 6 4 --- 5 3 11 5 5 1 --- 2 Respiratory System Respiratory Disorder Sinusitis Yawn 7 4 4 5 3 --- --- --- 2 --- --- < 1 Special Senses Abnormal Vision 2 1 3 1 Urogenital System Abnormal Ejaculation a Female Genital Disorder a Impotence a 25 4 4 2 1 3 13 5 9 2 1 1 a Dose Dependent Adverse Reactions MDD A comparison of adverse reaction rates in a fixed-dose study comparing paroxetine tablets 10 mg, 20 mg, 30 mg, and 40 mg once daily with placebo in the treatment of MDD revealed dose dependent adverse reactions, as shown in Table 7: Table 7. Adverse Reactions (>=5% of Paroxetine -Treated Patients and >= Twice the Rate of Placebo) (in a Dose-Comparison Trial in the Treatment of MDD Body System/Preferred Term Placebo n = 51 % 10 mg n = 102 % Paroxetine Tablets 20 mg 30 mg n = 104 n = 101 % % 40 mg n = 102 % Body as a Whole Asthenia 0. 7 Dermatology Sweating 2. 8 Gastrointestinal Constipation 5. 7 Decreased Appetite 2. 9 Diarrhea 7. 7 Dry Mouth 2. 6 Nausea 13. 3 Nervous System Anxiety 0. 9 Dizziness 3. 7 Nervousness 0. 9 Paresthesia 0. 9 Somnolence 7. 7 Special Senses Blurred Vision 2. 8 Urogenital System Abnormal Ejaculation a 0. 0 Impotence 0. 9 Male Genital Disorders 0. 7 OCD In a fixed-dose study comparing placebo and paroxetine tablets 20 mg, 40 mg, and 60 mg in the treatment of OCD, there was no clear relationship between adverse reactions and the dose of paroxetine tablets to which patients were assigned. PD In a fixed-dose study comparing placebo and paroxetine tablets 10 mg, 20 mg, and 40 mg in the treatment of PD, the following adverse reactions were shown to be dose-dependent: asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. SAD In a fixed-dose study comparing placebo and paroxetine tablets 20 mg, 40 mg and 60 mg in the treatment of SAD, for most of the adverse reactions, there was no clear relationship between adverse reactions and the dose of paroxetine tablets to which patients were assigned. GAD In a fixed-dose study comparing placebo and paroxetine tablets 20 mg and 40 mg in the treatment of GAD, the following adverse reactions were shown to be dose-dependent: asthenia, constipation, and abnormal ejaculation. PTSD In a fixed-dose study comparing placebo and paroxetine tablets 20 mg and 40 mg in the treatment of PTSD, the following adverse reactions were shown to be dose-dependent: impotence and abnormal ejaculation. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, 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 healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. The percentage of patients reporting symptoms of sexual dysfunction in males and females with MDD, OCD, PD, SAD, GAD, and PTSD are displayed in Table 8. Adverse Reactions Related to Sexual Dysfunction in Patients Treated with Paroxetine Tablets in Clinical Trials of MDD, OCD, PD, SAD, GAD, and PTSD Paroxetine Tablets Placebo n (males) 1,446 % 1,042 % Decreased Libido 6 to15 0 to 5 Ejaculatory Disturbance 13 to 28 0 to 2 Impotence 2 to 9 0 to 3 n (females) 1,822 % 1,340 % Decreased Libido 0 to 9 0 to 2 Orgasmic Disturbance 2 to 9 0 to 1 Paroxetine tablets treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. Hallucinations In pooled clinical trials of paroxetine tablets, hallucinations were observed in 0. 2% of paroxetine tablets-treated patients compared to 0. 1% of patients receiving placebo. Less Common Adverse Reactions The following adverse reactions occurred during the clinical studies of paroxetine tablets and are not included elsewhere in the labeling. Adverse reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients. Body as a Whole Infrequent rare: Cardiovascular System Frequent: infrequent: migraine, postural hypotension, syncope; rare: fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headache, ventricular extrasystoles. Digestive System Infrequent: rare: Endocrine System Rare: Hemic and Lymphatic Systems Infrequent: rare: Metabolic and Nutritional Frequent: 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: The following reactions have been identified during post approval use of paroxetine tablets. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), syndrome of inappropriate ADH secretion, prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, oculogyric crisis which has been associated with concomitant use of pimozide; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), vasculitic syndromes (such as Henoch-Schönlein purpura), and premature births in pregnant women. There has been a case report of severe hypotension when paroxetine tablets were added to chronic metoprolol treatment.

Paroxetine tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5. 2 7 Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions ( 5. 3 7 Taking pimozide because of risk of QT prolongation [see Warnings and Precautions ( 5. 3 7 With known hypersensitivity (e. , anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any of the inactive ingredients in paroxetine tablets [see Adverse Reactions ( 6. 2 Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI. 3 7 Concomitant use of pimozide or thioridazine. 3 7 Known hypersensitivity to paroxetine or to any of the inactive ingredients in paroxetine tablets.

Pregnancy 8. 1 Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5. 5 Paroxetine tablets are associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiac malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data). There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine tablets during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD en dash 60 mg) on an mg/m 2 2 See Data The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5. 5 Fetal/Neonatal adverse reactions Neonates exposed to paroxetine tablets and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5. 2 Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996 en dash 2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include an approximately 2 to 2. 5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defect (pooled OR 2. 38, 95% CI 1. Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD en dash 60 mg) on an mg/m 2 2 Risk Summary Data from the published literature report the presence of paroxetine in human milk (see Data). There are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk (see Clinical Considerations). There are no data on the effect of paroxetine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for paroxetine tablets and any potential adverse effects on the breastfed child from paroxetine tablets or from underlying maternal condition. Clinical Considerations Infants exposed to paroxetine tablets should be monitored for agitation, irritability, poor feeding and poor weight gain. Data Published literature suggests the presence of paroxetine in human milk with relative infant doses ranging between 0. 2%, and a milk/plasma ratio of <1. No significant amounts were detected in the plasma of infants after breastfeeding. Infertility Male Based on findings from clinical studies, paroxetine may affect sperm quality which may impair fertility; it is not known if this effect is reversible [see Nonclinical Toxicology ( 13. 1 The safety and effectiveness of paroxetine tablets in pediatric patients have not been established [see Box Warning]. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions ( 5. 1 In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paroxetine tablets and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with paroxetine tablets in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. In premarketing clinical trials with paroxetine tablets, 17% of patients treated with paroxetine tablets (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; however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see Dosage and Administration ( 2. 3 SSRIs including paroxetine tablets, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5. 7 Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of paroxetine tablets should be reduced in patients with severe renal impairment and in patients with severe hepatic impairment [see Dosage and Administration ( 2.

Table 9 presents clinically significant drug interactions with paroxetine tablets. Table 9: Clinically Significant Drug Interactions with Paroxetine Tablets Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine tablets, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine tablets are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2. 2 Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine tablets are contraindicated in patients taking pimozide or thioridazine [see Contraindications ( 4 Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine tablets increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine tablets and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5. 2 Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine tablets may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine Tablets and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions ( 5. 5 Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine tablets are highly bound to plasma protein. The concomitant use of paroxetine tablets with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine tablets or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of paroxetine Tablets or other protein-bound drugs as warranted. Examples Warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine tablets are a CYP2D6 inhibitor [see Clinical Pharmacology ( 12. 3 Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine Tablets use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine tablets are discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine tablets may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions ( 5. 11 Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine Tablets significantly decreased plasma levels of paroxetine Tablets. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy). Drugs Highly Bound to Plasma Protein 7 Drugs Metabolized by CYP2D6 7 Concomitant use with tamoxifen 5.

OVERDOSAGE
The following have been reported with paroxetine tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a paroxetine overdose. Consider contacting a poison center (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.
NONCLINICAL TOXICOLOGY
Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). These doses are up to 2 (mouse) and 3 (rat) times the MRHD of 60 mg on a mg/m 2 Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro in vivo in vivo in vitro Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is 2 times the MRHD of 60 mg on a mg/m 2 2
CLINICAL STUDIES
The efficacy of paroxetine tablets as a treatment for major depressive disorder (MDD) has been established in 6 placebo-controlled studies of patients with MDD (aged 18 to 73). In these studies, paroxetine tablets were shown to be statistically significantly more effective than placebo in treating MDD 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 tablets were statistically significantly better than placebo in improvement of the HDRS sub-factor scores, including the depressed mood item, sleep disturbance factor, and anxiety factor. Long-term efficacy of paroxetine tablets for treatment of MDD in outpatients was demonstrated in a randomized withdrawal study. Patients who responded to paroxetine tablets (HDRS total score <8) during an initial 8-week open-label treatment phase were then randomized to continue paroxetine tablets or placebo, for up to 1 year. Patients treated with paroxetine tablets demonstrated a statistically significant lower relapse rate during the withdrawal phase (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients. The effectiveness of paroxetine tablets 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 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. In study 1, a dose-range finding study, patients received fixed daily doses of paroxetine tablets 20 mg, 40 mg, or 60 mg. Study 1 demonstrated that daily doses of paroxetine tablets 40 mg and 60 mg are effective in the treatment of OCD. Patients receiving doses of paroxetine tablets 40 mg and 60 mg experienced a mean reduction of approximately 6 and 7 points, respectively, on the YBOCS total score which was statistically 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 tablets 20 mg to 60 mg daily with clomipramine 25 mg to 250 mg daily or placebo). In this study, patients receiving paroxetine tablets experienced a mean reduction of approximately 7 points on the YBOCS total score, which was statistically significantly greater than the mean reduction of approximately 4 points in placebo-treated patients. The following table provides the outcome classification by treatment group on Global Improvement items of the Clinical Global Impression (CGI) scale for Study 1. Table 10 Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 in Patients with OCD Outcome Placebo Paroxetine Tablets 20 mg Paroxetine Tablets 40 mg Paroxetine Tablets 60 mg Classification (n = 74) (n = 75) (n = 66) (n = 66) % % % % 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 efficacy of paroxetine tablets for the treatment of OCD was established in a long-term extension to Study 1. Patients who responded to paroxetine tablets during the 3-month double-blind phase and a 6-month extension on open-label paroxetine tablets 20 mg to 60 mg daily were randomized to either paroxetine tablets or placebo in a 6-month double-blind relapse prevention phase. Patients randomized to paroxetine tablets were statistically significantly less likely to relapse than placebo-treated patients. The effectiveness of paroxetine tablets in the treatment of panic disorder (PD) was demonstrated in three 10- to 12-week multicenter, placebo-controlled studies of adult outpatients (Studies 1, 2, and 3). Patients had PD (DSM-IIIR), with or without agoraphobia. In these studies, paroxetine tablets were shown to be statistically significantly more effective than placebo in treating PD 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 received fixed doses of paroxetine tablets 10 mg, 20 mg, or 40 mg daily or placebo. A statistically significant difference from placebo was observed only for the paroxetine tablets 40 mg daily group. At endpoint, 76% of patients receiving paroxetine tablets 40 mg daily were free of panic attacks, compared to 44% of placebo-treated patients. Study 2 was a 12-week flexible-dose study comparing paroxetine tablets 10 mg to 60 mg daily and placebo. At endpoint, 51% of paroxetine tablets -treated patients were free of panic attacks compared to 32% of placebo-treated patients. Study 3 was a 12-week flexible-dose study comparing paroxetine tablets 10 mg to 60 mg daily to placebo in patients concurrently receiving standardized cognitive behavioral therapy. At endpoint, 33% of the paroxetine tablets -treated patients showed a reduction to 0 or 1 panic attacks compared to 14% of placebo-treated patients. In Studies 2 and 3, the mean paroxetine tablets dose for completers at endpoint was approximately 40 mg daily. Long-term efficacy of paroxetine tablets in PD was demonstrated in an extension to Study 1. Patients who responded to paroxetine tablets during the 10-week double-blind phase and during a 3-month double-blind extension phase were randomized to either paroxetine tablets 10 mg, 20 mg, or 40 mg daily 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. The effectiveness of paroxetine tablets in the treatment of social anxiety disorder (SAD) was demonstrated in three 12-week, multicenter, placebo-controlled studies (Studies 1, 2, and 3) of adult outpatients with SAD (DSM-IV). In these studies, the effectiveness of paroxetine tablets compared to placebo was evaluated on the basis of (1) the proportion of responders, as defined by a Clinical Global Impression (CGI) Improvement score of 1 (very much improved) or 2 (much improved), and (2) change from baseline in the Liebowitz Social Anxiety Scale (LSAS). Studies 1 and 2 were flexible-dose studies comparing paroxetine tablets 20 mg to 50 mg daily and placebo. Paroxetine tablets 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 tablets-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-tablets- and placebo-treated patients, respectively. Study 3 was a 12-week study comparing fixed doses of paroxetine tablets 20 mg, 40 mg, or 60 mg daily with placebo. Paroxetine tablets 20 mg was statistically 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 paroxetine tablets 40 mg and 60 mg daily dose groups. There was no indication in this study of any additional benefit for doses higher than 20 mg daily. Subgroup analyses generally did not indicate differences in treatment outcomes as a function of age, race, or gender. The effectiveness of paroxetine tablets in the treatment of generalized anxiety disorder (GAD) was demonstrated in two 8-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients with GAD (DSM-IV). Study 1 was an 8-week study comparing fixed doses of paroxetine tablets 20 mg or 40 mg daily with placebo. Doses of paroxetine tablets 20 mg or 40 mg were both demonstrated to be statistically 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 paroxetine tablets 40 mg daily dose compared to the 20 mg daily dose. Study 2 was a flexible-dose study comparing paroxetine tablets 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, a flexible-dose study comparing paroxetine tablets 20 mg to 50 mg daily to placebo, 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 long-term trial, 566 patients meeting DSM-IV criteria for GAD, who had responded during a single-blind, 8-week acute treatment phase with paroxetine tablets 20 mg to 50 mg daily, 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 continuing to receive paroxetine tablets experienced a statistically significantly lower relapse rate over the subsequent 24 weeks compared to those receiving placebo. The effectiveness of paroxetine tablets in the treatment of Posttraumatic Stress Disorder (PTSD) was demonstrated in two 12-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients who met DSM-IV criteria for PTSD. The mean duration of PTSD symptoms for the 2 studies combined was 13 years (ranging from 0. 1 year to 57 years). The percentage of patients with secondary MDD or non-PTSD anxiety disorders in the combined 2 studies was 41% (356 out of 858 patients) and 40% (345 out of 858 patients), respectively. Study outcome was assessed by (1) the Clinician-Administered PTSD Scale Part 2 (CAPS-2) score and (2) the Clinical Global Impression-Global Improvement Scale (CGI-I). The CAPS-2 is a multi-item instrument that measures 3 aspects of PTSD with the following symptom clusters: Reexperiencing/intrusion, avoidance/numbing and hyperarousal. The 2 primary outcomes for each trial were (1) change from baseline to endpoint on the CAPS-2 total score (17 items), and (2) proportion of responders on the CGI-I, where responders were defined as patients having a score of 1 (very much improved) or 2 (much improved). Study 1 was a 12-week study comparing fixed doses of paroxetine tablets 20 mg or 40 mg daily to placebo. Doses of paroxetine tablets 20 mg and 40 mg were demonstrated to be statistically significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I. There was not sufficient evidence in this study to suggest a greater benefit for the 40 mg daily dose compared to the 20 mg daily dose. Study 2 was a 12-week flexible-dose study comparing paroxetine tablets 20 mg to 50 mg daily to placebo. Paroxetine tablets were demonstrated to be significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I. A third study, a flexible-dose study comparing paroxetine tablets 20 mg to 50 mg daily to placebo, demonstrated paroxetine tablets to be statistically significantly superior to placebo on change from baseline for CAPS-2 total score, but not on proportion of responders on the CGI-I. The majority of patients in these trials were women (68% women: 377 out of 551 subjects in Study 1 and 66% women: 202 out of 303 subjects in Study 2). Subgroup analyses did not indicate differences in treatment outcomes as a function of gender. There were an insufficient number of patients who were 65 years and older or were non-Caucasian to conduct subgroup analyses on the basis of age or race, respectively.
Medication Guide
MEDICATION GUIDE Paroxetine Tablets USP (PA-rox-eh-tine) What is the most important information I should know about paroxetine tablets? Paroxetine tablets can cause serious side effects, including: Increased risk of suicidal thoughts or actions. first few months of treatment or when the dose is changed Paroxetine tablets are not for use in children. Depression or other mental illnesses are the most important causes of suicidal thoughts and actions. How can I watch for and try to prevent suicidal thoughts and actions? Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the does is changed. Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, 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 and talking more than what is normal for you other unusual changes in behavior or mood What are Paroxetine Tablets? Paroxetine tablets are a prescription medicine used in adults to treat: A certain type of depression called Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD) Do not take Paroxetine Tablets if you: take a monoamine oxidase inhibitor (MAOI) have stopped taking an MAOI in the last 14 days are being treated with the antibiotic linezolid or the intravenous methylene blue are taking pimozide are taking thioridazine 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. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine tablets. Before taking paroxetine tablets, tell your healthcare provider about all your medical conditions, including if you: have heart problems have or had bleeding problems have, or have a family history of, bipolar disorder, mania or hypomania have or had seizures or convulsions have glaucoma (high pressure in the eye) have low sodium levels in your blood have bone problems have kidney or liver problems are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby. Taking paroxetine tablets during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. Taking paroxetine tablets during your third trimester of pregnancy may cause your baby to have breathing, temperature, and feeding problems, low muscle tone, and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine tablets. are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine tablets. Tell your healthcare provider about all the medicines you take Paroxetine tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine tablets may affect the way other medicines work and other medicines may affect the way paroxetine tablets work. Especially tell your healthcare provider if you take: medicines used to treat migraine headaches called triptans tricyclic antidepressants lithium tramadol, fentanyl, meperidine, methadone, or other opioids tryptophan buspirone amphetamines St. John’s Wort medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin diuretics tamoxifen medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine tablets without talking to your healthcare provider first. Stopping paroxetine tablets suddenly may cause you to have serious side effects. See, “What are the possible side effects of Paroxetine Tablets?” 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. Take paroxetine tablets 1 time each day in the morning. Paroxetine tablets may be taken with or without food. If you take too many paroxetine tablets, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of Paroxetine Tablets? Paroxetine Tablets can cause serious side effects, including: See, “What is the most important information I should know about Paroxetine Tablets?” Serotonin syndrome. Call your healthcare provider or go to the nearest hospital emergency room right away agitation sweating seeing or hearing things that are not real (hallucinations) flushing confusion high body temperature (hyperthermia) coma shaking (tremors), stiff muscles, or muscle twitching fast heart beat loss of coordination changes in blood pressure seizures dizziness nausea, vomiting, diarrhea Eye problems (angle-closure glaucoma). . Medicine interactions. . Seizures (convulsions). Manic episodes. greatly increased energy severe problems sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual Discontinuation syndrome. nausea electric shock feeling (paresthesia) tiredness sweating tremor problems sleeping changes in your mood anxiety hypomania irritability and agitation confusion ringing in your ears (tinnitus) dizziness headache seizures Low sodium levels in your blood (hyponatremia). headache difficulty concentrating memory changes confusion weakness and unsteadiness on your feet which can lead to falls In more severe or more sudden cases, signs and symptoms include: seeing or hearing things that are not real (hallucinations) fainting seizures coma stopping breathing (respiratory arrest) Abnormal bleeding. Bone fractures. Sexual problems (dysfunction). Symptoms in males may include: Delayed ejaculation or inability to have an ejaculation Decreased sex drive Problems getting or keeping an erection Symptoms in females may include: Decreased sex drive Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine tablets. There may be treatments your healthcare provider can suggest. The most common side effects of Paroxetine Tablets include: male and female sexual function problems weakness (asthenia) constipation decreased appetite diarrhea dizziness dry mouth infection problems sleeping nausea nervousness sleepiness sweating shaking (tremor) yawning These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-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 and all medicines out of the reach of children. General information about the safe and effective use of Paroxetine Tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take 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 symptoms that you have. It may harm them. 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. For more information about paroxetine tablets call 1-866-257-2597. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 12/2024 Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

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