PAROXETINE- paroxetine hydrochloride hemihydrate tablet, film coated Mylan Pharmaceuticals Inc.----------

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use PAROXETINE TABLETSsafely and effectively. See full prescribing information for PAROXETINE TABLETS. PAROXETINE tablets, for oral use Initial U.S. Approval: 1992

WARNING: SUICIDAL THOUGHTS AND BEHAVIORSSee full prescribing information for complete boxed warning.

Increased risk of suicidal thoughts and behavior in pediatric and young adult patientstaking antidepressants. Closely monitor all antidepressant treated patients for clinicalworsening and emergence of suicidal thoughts and behaviors. Paroxetine tablets arenot approved for use in pediatric patients. (5.1, 8.4)

RECENT MAJOR CHANGESWarnings and Precautions, Sexual Dysfunction(5.13) 9/2021

INDICATIONS AND USAGEParoxetine tablets are a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatmentof (1):

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DOSAGE AND ADMINISTRATION

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Indication Starting Daily Dose Maximum Daily DoseMDD 20 mg 50 mgOCD 20 mg 60 mgPD 10 mg 60 mg

PTSD 20 mg 50 mg

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DOSAGE FORMS AND STRENGTHS

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CONTRAINDICATIONS

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WARNINGS AND PRECAUTIONS

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ADVERSE REACTIONSMost 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 Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

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USE IN SPECIFIC POPULATIONS

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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)

Recommended starting dosage for SAD and GAD is 20 mg daily. (2.3)Elderly patients, patients with severe renal impairment or severe hepatic impairment: Starting dosageis 10 mg daily. Maximum dosage is 40 mg daily. (2.4)When discontinuing paroxetine tablets, reduce dosage gradually. (2.6, 5.7)

Tablets: 10 mg, scored; 20 mg, scored; 30 mg; and 40 mg tablets. (3)

Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing aMAOI. (4, 5.3, 7)Concomitant use of pimozide or thioridazine. (4, 5.3, 7)Known hypersensitivity to paroxetine or to any of the inactive ingredients in paroxetine tablets. (4)

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI,SNRI, triptans), but also when taken alone. If occurs, discontinue paroxetine tablets and initiatesupportive measures. (5.2)Embryofetal and Neonatal Toxicity: Can cause fetal and neonatal harm. Increased risk ofcardiovascular malformations with exposure during the first trimester. Exposure in late pregnancymay lead to an increased risk for persistent pulmonary hypertension of the newborn. (5.4, 8.1)Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, otherantiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. (5.5)Activation of Mania/Hypomania: Screen patients for bipolar disorder. (5.6)Seizures: Use with caution in patients with seizure disorders. (5.8)Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreatedanatomically narrow angles treated with antidepressants. (5.9)Sexual Dysfunction: Paroxetine tablets may cause symptoms of sexual dysfunction (5.13)

Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage ofparoxetine tablets or other protein-bound drugs (e.g., warfarin) as warranted. (7)Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. (7)Concomitant Use with Tamoxifen: Consider use of an alternative antidepressant with little or noCYP2D6 inhibition. (5.11, 7)

Pregnancy: Can cause fetal and neonatal harm. Advise women of potential risk to the fetus. (8.1)Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug tomother. (8.3)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.Revised: 10/2021

FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: SUICIDAL THOUGHTS AND BEHAVIORS1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION

2.1 Administration Information2.2 Recommended Dosage for MDD, OCD, PD, and PTSD2.3 Recommended Dosage for SAD and GAD2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine Tablets2.5 Recommended Dosage for Elderly Patients, Patients with Severe RenalImpairment, and Patients with Severe Hepatic Impairment2.6 Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI)2.7 Discontinuation of Treatment With Paroxetine Tablets

3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults5.2 Serotonin Syndrome5.3 Drug Interactions Leading to QT Prolongation5.4 Embryofetal and Neonatal Toxicity5.5 Increased Risk of Bleeding5.6 Activation of Mania or Hypomania5.7 Discontinuation Syndrome5.8 Seizures5.9 Angle-Closure Glaucoma5.10 Hyponatremia5.11 Reduction of Efficacy of Tamoxifen5.12 Bone Fracture5.13 Sexual Dysfunction

6 ADVERSE REACTIONS6.1 Clinical Trials Experience6.2 Postmarketing Experience

7 DRUG INTERACTIONS8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal and Hepatic Impairment

10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES14.1 Major Depressive Disorder14.2 Obsessive Compulsive Disorder14.3 Panic Disorder14.4 Social Anxiety Disorder14.5 Generalized Anxiety Disorder14.6 Posttraumatic Stress Disorder

16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*

FULL PRESCRIBING INFORMATION

WARNING: SUICIDAL THOUGHTS AND BEHAVIORSAntidepressants increased the risk of suicidal thoughts and behaviors inpediatric and young adult patients in short-term studies. Closely monitorall antidepressant-treated patients for clinical worsening, and foremergence of suicidal thoughts and behaviors [see Warnings andPrecautions (5.1)]. Paroxetine tablets are not approved for use inpediatric patients [see Use in Specific Populations (8.4)].

Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGEParoxetine tablets are indicated in adults for the treatment of:

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2 DOSAGE AND ADMINISTRATION

2.1 Administration InformationAdminister paroxetine tablets as a single daily dose in the morning, with or without food.

2.2 Recommended Dosage for MDD, OCD, PD, and PTSDThe recommended starting dosages and maximum dosages of paroxetine tablets inpatients with MDD, OCD, PD, and PTSD are presented in Table 1.In patients with an inadequate response, increase dosage in increments of 10 mg perday at intervals of at least 1 week, depending on tolerability.

Table 1: Recommended Daily Dosage of Paroxetine Tablets in Patients withMDD, OCD, PD, and PTSD

Indication Starting Dose Maximum DoseMDD 20 mg 50 mgOCD 20 mg 60 mgPD 10 mg 60 mg

PTSD 20 mg 50 mg

2.3 Recommended Dosage for SAD and GAD

SADThe starting and recommended dosage in patients with SAD is 20 mg daily. In clinicaltrials the effectiveness of paroxetine tablets was demonstrated in patients dosed in arange of 20 mg to 60 mg daily. While the safety of paroxetine tablets has beenevaluated in patients with SAD at doses up to 60 mg daily, available information does notsuggest any additional benefit for doses above 20 mg daily [see Clinical Studies (14.4)].

GADThe starting and recommended dosage in patients with GAD is 20 mg daily. In clinicaltrials the effectiveness of paroxetine tablets in GAD was demonstrated in patients dosedin a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greaterbenefit 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 perday at intervals of at least 1 week, depending on tolerability.

2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine TabletsPrior to initiating treatment with paroxetine tablets or another antidepressant, screenpatients for a personal or family history of bipolar disorder, mania, or hypomania [seeWarnings and Precautions (5.6)].

2.5 Recommended Dosage for Elderly Patients, Patients with Severe RenalImpairment, and Patients with Severe Hepatic ImpairmentThe recommended initial dosage is 10 mg per day for elderly patients, patients withsevere renal impairment, and patients with severe hepatic impairment. Dosage shouldnot exceed 40 mg/day.

2.6 Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI)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 afterstopping paroxetine tablets before starting an MAOI antidepressant [seeContraindications (4), Warnings and Precautions (5.2)].

2.7 Discontinuation of Treatment With Paroxetine TabletsAdverse reactions may occur upon discontinuation of paroxetine tablets [see Warningsand Precautions (5.7)]. Gradually reduce the dosage rather than stopping paroxetinetablets abruptly whenever possible.

Major depressive disorder (MDD)Obsessive compulsive disorder (OCD)Panic disorder (PD)Social anxiety disorder (SAD)Generalized anxiety disorder (GAD)Posttraumatic stress disorder (PTSD)

3 DOSAGE FORMS AND STRENGTHSParoxetine Tablets, USP are available containing paroxetine hydrochloride, USP(hemihydrate) equivalent to 10 mg, 20 mg, 30 mg or 40 mg of paroxetine.

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4 CONTRAINDICATIONSParoxetine tablets are contraindicated in patients:

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5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Adolescents and Young AdultsIn pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and otherantidepressant classes) that included approximately 77,000 adult patients and 4,500pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients.There was considerable variation in risk of suicidal thoughts and behaviors amongdrugs, but there was an increased risk identified in young patients for most drugsstudied. There were differences in absolute risk of suicidal thoughts and behaviorsacross the different indications, with the highest incidence in patients with MDD. Thedrug-placebo differences in the number of cases of suicidal thoughts and behaviors per1000 patients treated are provided in Table 2.

Table 2: Risk Differences of the Number of Patients with Suicidal Thoughtsand Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in

Pediatric and Adult PatientsAge Range Drug-Placebo Difference in Number of Patients with

Suicidal Thoughts and Behaviors per 1,000 PatientsTreated

Increases Compared to Placebo< 18 years old 14 additional cases18-24 years old 5 additional cases

Decreases Compared to Placebo25-64 years old 1 fewer case≥ 65 years old 6 fewer cases

Paroxetine tablets are not approved for use in pediatric patients.It is unknown whether the risk of suicidal thoughts and behaviors in children,adolescents, and young adults extends to longer-term use, i.e., beyond four months.However, there is substantial evidence from placebo-controlled maintenance trials inadults with MDD that antidepressants delay the recurrence of depression and thatdepression itself is a risk factor for suicidal thoughts and behaviors.Monitor all antidepressant-treated patients for any indication for clinical worsening andemergence of suicidal thoughts and behaviors, especially during the initial few months ofdrug therapy, and at times of dosage changes. Counsel family members or caregiversof patients to monitor for changes in behavior and to alert the healthcare provider.Consider changing the therapeutic regimen, including possibly discontinuing paroxetinetablets, in patients whose depression is persistently worse, or who are experiencingemergent suicidal thoughts or behaviors.

5.2 Serotonin Syndrome

The 10 mg tablets are blue, film-coated, modified capsule-shaped, scored tabletsdebossed with M on one side of the tablet and N to the left of the score and 1 tothe right of the score on the other side.The 20 mg tablets are blue, film-coated, modified capsule-shaped, scored tabletsdebossed with M on one side of the tablet and N to the left of the score and 2 tothe right of the score on the other side.The 30 mg tablets are blue, film-coated, round, unscored tablets debossed with Mover N3 on one side of the tablet and blank on the other side.The 40 mg tablets are blue, film-coated, round, unscored tablets debossed with Mover N4 on one side of the tablet and blank on the other side.

Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid andintravenous methylene blue) because of an increased risk of serotonin syndrome[see Warnings and Precautions (5.2), Drug Interactions (7)].Taking thioridazine because of risk of QT prolongation [see Warnings andPrecautions (5.3) and Drug Interactions (7)].Taking pimozide because of risk of QT prolongation [see Warnings and Precautions(5.3), Drug Interactions (7)].With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnsonsyndrome) to paroxetine or any of the inactive ingredients in paroxetine tablets[see Adverse Reactions (6.1), (6.2)].

SSRIs, including paroxetine tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergicdrugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,tryptophan, buspirone, amphetamines and St. John’s Wort) and with drugs that impairmetabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7.1)].Serotonin syndrome can also occur when these drugs are used alone.Serotonin syndrome symptoms may include mental status changes (e.g., agitation,hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile bloodpressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms(e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/orgastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).The concomitant use of paroxetine tablets with MAOIs is contraindicated. In addition, donot initiate paroxetine tablets in a patient being treated with MAOIs such as linezolid orintravenous methylene blue. No reports involved the administration of methylene blue byother routes (such as oral tablets or local tissue injection) or at lower doses. If it isnecessary to initiate treatment with an MAOI such as linezolid or intravenous methyleneblue in a patient taking paroxetine tablets discontinue paroxetine tablets before initiatingtreatment with the MAOI [see Contraindications (4), Drug Interactions (7)].Monitor all patients taking paroxetine tablets for the emergence of serotonin syndrome.Discontinue treatment with paroxetine tablets and any concomitant serotonergic agentsimmediately if the above symptoms occur, and initiate supportive symptomatictreatment. If concomitant use of paroxetine tablets with other serotonergic drugs isclinically warranted, inform patients of the increased risk for serotonin syndrome andmonitor for symptoms.

5.3 Drug Interactions Leading to QT ProlongationThe CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazineand pimozide. Since thioridazine and pimozide given alone produce prolongation of theQTc interval and increase the risk of serious ventricular arrhythmias, the use ofparoxetine tablets is contraindicated in combination with thioridazine and pimozide [seeContraindications (4), Drug Interactions (7),Clinical Pharmacology (12.3)].

5.4 Embryofetal and Neonatal ToxicityParoxetine tablets can cause fetal harm when administered to a pregnant woman.Epidemiological studies have shown that infants exposed to paroxetine in the firsttrimester of pregnancy have an increased risk of cardiovascular malformations.Exposure to paroxetine in late pregnancy may lead to an increased risk for persistentpulmonary hypertension of the newborn (PPNH) and/or neonatal complications requiringprolonged hospitalization, respiratory support, and tube feeding.If paroxetine tablets are used during pregnancy, or if the patient becomes pregnantwhile taking paroxetine tablets, the patient should be apprised of the potential hazard tothe fetus [see Use in Specific Populations (8.1)].

5.5 Increased Risk of BleedingDrugs that interfere with serotonin reuptake inhibition, including paroxetine tablets,increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and otheranticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugsthat interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.Bleeding events related to drugs that interfere with serotonin reuptake have rangedfrom ecchymoses, hematomas, epistaxis, and petechiae to life-threateninghemorrhages.Inform patients about the increased risk of bleeding associated with the concomitantuse of paroxetine tablets and antiplatelet agents or anticoagulants. For patients takingwarfarin, carefully monitor the international normalized ratio.

5.6 Activation of Mania or HypomaniaIn patients with bipolar disorder, treating a depressive episode with paroxetine tablets oranother antidepressant may precipitate a mixed/manic episode. During controlled clinicaltrials of paroxetine tablets, hypomania or mania occurred in approximately 1% ofparoxetine tablets-treated unipolar patients compared to 1.1% of active-control and0.3% of placebo-treated unipolar patients. Prior to initiating treatment with paroxetinetablets, screen patients for any personal or family history of bipolar disorder, mania, orhypomania.

5.7 Discontinuation SyndromeAdverse reactions after discontinuation of serotonergic antidepressants, particularlyafter abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability,agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shocksensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia,hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abruptcessation is recommended whenever possible [see Dosage and Administration (2.7)].

During clinical trials of GAD and PTSD, gradual decreases in the daily dose by 10 mg/dayat weekly intervals followed by 1 week at 20 mg/day was used before treatment wasdiscontinued. The following adverse reactions were reported at an incidence of 2% orgreater for paroxetine tablets and were at least twice that reported for placebo:Abnormal dreams, paresthesia, and dizziness. Adverse reactions have been reportedupon discontinuation of treatment with paroxetine tablets in pediatric patients. Thesafety and effectiveness of paroxetine tablets in pediatric patients have not beenestablished [see Boxed Warning, Warnings and Precautions (5.1), Use in SpecificPopulations (8.4)].

5.8 SeizuresParoxetine tablets and oral suspension have not been systematically evaluated inpatients with seizure disorders. Patients with history of seizures were excluded fromclinical studies. During clinical studies, seizures occurred in 0.1% of patients treated withparoxetine tablets. Paroxetine tablets should be prescribed with caution in patients witha seizure disorder. Discontinue paroxetine tablets in any patient who develops seizures.

5.9 Angle-Closure GlaucomaThe pupillary dilation that occurs following use of many antidepressant drugs includingparoxetine tablets may trigger an angle closure attack in a patient with anatomicallynarrow angles who does not have a patent iridectomy. Cases of angle-closure glaucomaassociated with use of paroxetine tablets have been reported. Avoid use ofantidepressants, including paroxetine tablets in patients with untreated anatomicallynarrow angles.

5.10 HyponatremiaHyponatremia may occur as a result of treatment with SSRIs, including paroxetinetablets. Cases with serum sodium lower than 110 mmol/L have been reported. Signs andsymptoms of hyponatremia include headache, difficulty concentrating, memoryimpairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs andsymptoms associated with more severe and/or acute cases have included hallucination,syncope, seizure, coma, respiratory arrest, and death. In many cases, thishyponatremia appears to be the result of the syndrome of inappropriate antidiuretichormone secretion (SIADH).In patients with symptomatic hyponatremia, discontinue paroxetine tablets and instituteappropriate medical intervention. Elderly patients, patients taking diuretics, and thosewho are volume-depleted may be at greater risk of developing hyponatremia with SSRIs[see Use in Specific Populations (8.5)].

5.11 Reduction of Efficacy of TamoxifenSome studies have shown that the efficacy of tamoxifen, as measured by the risk ofbreast cancer relapse/mortality, may be reduced with concomitant use of paroxetinetablets as a result of paroxetine’s irreversible inhibition of CYP2D6 and lower blood levelsof tamoxifen [see Drug Interactions (7)]. One study suggests that the risk may increasewith longer duration of coadministration. However, other studies have failed todemonstrate such a risk. When tamoxifen is used for the treatment or prevention ofbreast cancer, prescribers should consider using an alternative antidepressant with littleor no CYP2D6 inhibition.

5.12 Bone FractureEpidemiological studies on bone fracture risk during exposure to some antidepressants,including SSRIs, have reported an association between antidepressant treatment andfractures. There are multiple possible causes for this observation, and it is unknown towhat extent fracture risk is directly attributable to SSRI treatment.

5.13 Sexual DysfunctionUse of SSRIs, including paroxetine tablets, may cause symptoms of sexual dysfunction[see Adverse Reactions (6.1)]. In male patients, SSRI use may result in ejaculatory delayor failure, decreased libido, and erectile dysfunction. In female patients, SSRI use mayresult in decreased libido and delayed or absent orgasm. It is important for prescribersto inquire about sexual function prior to initiation of paroxetine tablets and to inquirespecifically about changes in sexual function during treatment, because sexual functionmay not be spontaneously reported. When evaluating changes in sexual function,obtaining a detailed history (including timing of symptom onset) is important becausesexual symptoms may have other causes, including the underlying psychiatric disorder.Discuss potential management strategies to support patients in making informeddecisions about treatment.

6 ADVERSE REACTIONSThe following adverse reactions are included in more detail in other sections of theprescribing information:

• Hypersensitivity reactions to paroxetine [see Contraindications (4)]

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6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reactionrates observed in the clinical trials of a drug cannot be directly compared to rates in theclinical trials of another drug and may not reflect the rates observed in practice.The safety data for paroxetine tablets are from:

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Adverse Reactions Leading to DiscontinuationTwenty percent (1,199/6,145) of patients treated with paroxetine tablets in clinical trialsin MDD and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and11.7% (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.e., thoseadverse reactions associated with dropout at a rate approximately twice or greater forparoxetine tablets compared to placebo) are presented in Table 3:

Table 3: Adverse Reactions Reported as Leading to Discontinuation (≥ 1% of Paroxetine Tablets Treated Patients andGreater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials

Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine tablets was not > 1% or was notgreater than or equal to 2 times the incidence of placebo.*

MDD OCD PD SAD GAD PTSDParoxetine

Tablets%

Placebo%

ParoxetineTablets

%

Placebo%

ParoxetineTablets

%

Placebo%

ParoxetineTablets

%

Placebo%

ParoxetineTablets

%

Placebo%

ParoxetineTablets

%

Placebo%

CNSSomnolence 2.3 0.7 - 1.9 0.3 3.4 0.3 2.0 0.2 2.8 0.6Insomnia - - 1.7 0 1.3 0.3 3.1 0 - -Agitation 1.1 0.5 - - -Tremor 1.1 0.3 - 1.7 0 1.0 0.2Anxiety - - - 1.1 0 - -Dizziness - - 1.5 0 1.9 0 1.0 0.2 - -GastrointestinalConstipation - 1.1 0 - -Nausea 3.2 1.1 1.9 0 3.2 1.2 4.0 0.3 2.0 0.2 2.2 0.6Diarrhea 1.0 0.3 -Dry mouth 1.0 0.3 - - -Vomiting 1.0 0.3 - 1.0 0 - -Flatulence 1.0 0.3 - -OtherAsthenia 1.6 0.4 1.9 0.4 2.5 0.6 1.8 0.2 1.6 0.2AbnormalEjaculation

1.6 0 2.1 0 4.9 0.6 2.5 0.5 - -

Sweating 1.0 0.3 - 1.1 0 1.1 0.2 - -Impotence - 1.5 0 - -LibidoDecreased

1.0 0 - -

Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1)]Serotonin Syndrome [see Warnings and Precautions (5.2)]Embryofetal and Neonatal 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)]

6-week clinical trials in MDD patients who received paroxetine tablets 20 mg to 50mg once daily12-week clinical trials in OCD patients who received paroxetine tablets 20 mg to 60mg once daily10- to 12-week clinical trials in PD patients who received paroxetine tablets 10 mgto 60 mg once daily12-week clinical trials in SAD patients who received paroxetine tablets 20 mg to 50mg once daily8-week clinical trials in GAD patients who received paroxetine tablets 10 mg to 50mg once daily12-week clinical trials in PTSD patients who received paroxetine tablets 20 mg to 50mg once daily

Incidence corrected for gender.

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Most Common Adverse ReactionsThe most commonly observed adverse reactions associated with the use of paroxetinetablets (incidence of 5% or greater and at least twice that for placebo) were:

MDD

Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia,tremor, nervousness, ejaculatory disturbance, and other male genital disorders.

OCD

Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor,sweating, impotence, and abnormal ejaculation.

PD

Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation,female genital disorders, and impotence.

SAD

Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor,libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.

GAD

Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libidodecreased, somnolence, tremor, sweating, and abnormal ejaculation.

PTSD

Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libidodecreased, abnormal ejaculation, female genital disorders, and impotence.

Adverse Reactions in Patients with MDDTable 4 presents the adverse reactions that occurred at an incidence of 1% or more andgreater than placebo in clinical trials of paroxetine tablets-treated patients with MDD.

Table 4: Adverse Reactions (≥ 1% of Paroxetine Tablets-Treated Patientsand Greater than Placebo) in 6-Week Clinical Trials for MDD

Body System/Adverse Reaction

Paroxetine Tablets(n = 421)

%

Placebo(n = 421)

%Body as a WholeHeadache 18 17Asthenia 15 6CardiovascularPalpitation 3 1Vasodilation 3 1DermatologicSweating 11 2Rash 2 1GastrointestinalNausea 26 9Dry Mouth 18 12Constipation 14 9Diarrhea 12 8Decreased Appetite 6 2Flatulence 4 2Oropharynx Disorder 2 0Dyspepsia 2 1MusculoskeletalMyopathy 2 1Myalgia 2 1Myasthenia 1 0Nervous SystemSomnolence 23 9Dizziness 13 6Insomnia 13 6Tremor 8 2Nervousness 5 3Anxiety 5 3Paresthesia 4 2Libido Decreased 3 0Drugged Feeling 2 1

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Confusion 1 0RespirationYawn 4 0Special SensesBlurred Vision 4 1Taste Perversion 2 0Urogenital SystemEjaculatory Disturbance 13 0Other Male Genital Disorders 10 0Urinary Frequency 3 1Urination Disorder 3 0Female Genital Disorders 2 0

Adverse Reactions in Patients with OCD, PD, and SADTable 5 presents adverse reactions that occurred at a frequency of 2% or more inclinical trials in patients with OCD, PD, and SAD.

Table 5. Adverse Reactions (≥ 2% of Paroxetine Tablets-Treated Patientsand Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and

SADBodySystem/PreferredTerm

ObsessiveCompulsive

Disorder

Panic Disorder Social AnxietyDisorder

ParoxetineTablets

(n = 542)%

Placebo(n =265)

%

ParoxetineTablets

(n = 469)%

Placebo(n =324)

%

ParoxetineTablets

(n = 425)%

Placebo(n =339)

%Body as a WholeAsthenia 22 14 14 5 22 14Abdominal Pain - - 4 3 - -Chest Pain 3 2 - - - -Back Pain - - 3 2 - -Chills 2 1 2 1 - -Trauma - - - - 3 1CardiovascularVasodilation 4 1 - - - -Palpitation 2 0 - - - -DermatologicSweating 9 3 14 6 9 2Rash 3 2 - - - -GastrointestinalNausea 23 10 23 17 25 7Dry Mouth 18 9 18 11 9 3Constipation 16 6 8 5 5 2Diarrhea 10 10 12 7 9 6Decreased Appetite 9 3 7 3 8 2Dyspepsia - - - - 4 2Flatulence - - - - 4 2Increased Appetite 4 3 2 1 - -Vomiting - - - - 2 1MusculoskeletalMyalgia - - - - 4 3Nervous SystemInsomnia 24 13 18 10 21 16Somnolence 24 7 19 11 22 5Dizziness 12 6 14 10 11 7Tremor 11 1 9 1 9 1Nervousness 9 8 - - 8 7Libido Decreased 7 4 9 1 12 1Agitation - - 5 4 3 1Anxiety - - 5 4 5 4Abnormal Dreams 4 1 - - - -ConcentrationImpaired

3 2 - - 4 1

Includes mostly “lump in throat” and “tightness in throat.”Percentage corrected for gender.Mostly “ejaculatory delay.”Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexualdysfunction,” and “impotence.”Includes mostly “difficulty with micturition” and “urinary hesitancy.”Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm.”

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¶†#

*

Depersonalization 3 0 - - - -Myoclonus 3 0 3 2 2 1Amnesia 2 1 - - - -Respiratory SystemRhinitis - - 3 0 - -Pharyngitis - - - - 4 2Yawn - - - - 5 1Special SensesAbnormal Vision 4 2 - - 4 1Taste Perversion 2 0 - - - -Urogenital SystemAbnormalEjaculation

23 1 21 1 28 1

Dysmenorrhea - - - - 5 4Female GenitalDisorder

3 0 9 1 9 1

Impotence 8 1 5 0 5 1Urinary Frequency 3 1 2 0 - -Urination Impaired 3 0 - - - -Urinary TractInfection

2 1 2 1 - -

Adverse Reactions in Patients with GAD and PTSDTable 6 presents adverse reactions that occurred at a frequency of 2% or more inclinical trials in patients with GAD and PTSD.

Table 6. Adverse Reactions (≥ 2% of Paroxetine Tablets-Treated Patientsand Greater than Placebo) in 8 to 12 Week Clinical Trials for GAD and PTSD

Body System/Preferred Term Generalized AnxietyDisorder

PosttraumaticStress Disorder

ParoxetineTablets

(n = 735)%

Placebo(n = 529)

%

ParoxetineTablets

(n = 676)%

Placebo(n = 504)

%

Body as a WholeAsthenia 14 6 12 4Headache 7 14 - -Infection 6 3 5 4Abdominal Pain 4 3Trauma 6 5CardiovascularVasodilation 3 1 2 1DermatologicSweating 6 2 5 1GastrointestinalNausea 20 5 19 8Dry Mouth 11 5 10 5Constipation 10 2 5 3Diarrhea 9 7 11 5Decreased Appetite 5 1 6 3Vomiting 3 2 3 2Dyspepsia - - 5 3Nervous SystemInsomnia 11 8 12 11Somnolence 15 5 16 5Dizziness 6 5 6 5Tremor 5 5 1 4Nervousness 4 3 - -Libido Decreased 9 2 5 2Abnormal Dreams 3Respiratory SystemRespiratory Disorder 7 5 - -Sinusitis 4 3 - -Yawn 4 - 2 <1Special SensesAbnormal Vision 2 1 3 1Urogenital SystemAbnormal Ejaculation 25 2 13 2

Percentage corrected for gender.

*

**

a

**

*

Female Genital Disorder 4 1 5 1Impotence 4 3 9 1

Dose Dependent Adverse Reactions

MDD

A comparison of adverse reaction rates in a fixed-dose study comparing paroxetinetablets 10 mg, 20 mg, 30 mg, and 40 mg once daily with placebo in the treatment ofMDD revealed dose dependent adverse reactions, as shown in Table 7:

Table 7. Adverse Reactions (≥ 5% of Paroxetine Tablets-Treated Patientsand ≥ Twice the Rate of Placebo) (in a Dose-Comparison Trial in the

Treatment of MDDPlacebo Paroxetine Tablets

Body System/PreferredTerm

n = 51%

10 mgn = 102

%

20 mgn = 104

%

30 mgn = 101

%

40 mgn = 102

%Body as a WholeAsthenia 0.0 2.9 10.6 13.9 12.7DermatologySweating 2.0 1.0 6.7 8.9 11.8GastrointestinalConstipation 5.9 4.9 7.7 9.9 12.7Decreased Appetite 2.0 2.0 5.8 4.0 4.9Diarrhea 7.8 9.8 19.2 7.9 14.7Dry Mouth 2.0 10.8 18.3 15.8 20.6Nausea 13.7 14.7 26.9 34.7 36.3Nervous SystemAnxiety 0.0 2.0 5.8 5.9 5.9Dizziness 3.9 6.9 6.7 8.9 12.7Nervousness 0.0 5.9 5.8 4.0 2.9Paresthesia 0.0 2.9 1.0 5.0 5.9Somnolence 7.8 12.7 18.3 20.8 21.6Tremor 0.0 0.0 7.7 7.9 14.7Special SensesBlurred Vision 2.0 2.9 2.9 2.0 7.8Urogenital SystemAbnormal Ejaculation 0.0 5.8 6.5 10.6 13.0Impotence 0.0 1.9 4.3 6.4 1.9Male Genital Disorders 0.0 3.8 8.7 6.4 3.7

OCD

In a fixed-dose study comparing placebo and paroxetine tablets 20 mg, 40 mg, and 60mg in the treatment of OCD, there was no clear relationship between adverse reactionsand 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 40mg in the treatment of PD, the following adverse reactions were shown to be dose-dependent: asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormalejaculation.

SAD

In a fixed-dose study comparing placebo and paroxetine tablets 20 mg, 40 mg and 60mg in the treatment of SAD, for most of the adverse reactions, there was no clearrelationship between adverse reactions and the dose of paroxetine tablets to whichpatients were assigned.

GAD

In a fixed-dose study comparing placebo and paroxetine tablets 20 mg and 40 mg in thetreatment 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 thetreatment of PTSD, the following adverse reactions were shown to be dose-dependent:impotence and abnormal ejaculation.

Percentage corrected for gender.

**

Male and Female Sexual DysfunctionAlthough changes in sexual desire, sexual performance, and sexual satisfaction oftenoccur as manifestations of a psychiatric disorder, they may also be a consequence ofSSRI treatment. However, reliable estimates of the incidence and severity of untowardexperiences involving sexual desire, performance, and satisfaction are difficult to obtain,however, in part because patients and healthcare providers may be reluctant to discussthem. Accordingly, estimates of the incidence of untoward sexual experience andperformance cited in labeling may underestimate their actual incidence.The percentage of patients reporting symptoms of sexual dysfunction in males andfemales with MDD, OCD, PD, SAD, GAD, and PTSD are displayed in Table 8.

Table 8. Adverse Reactions Related to Sexual Dysfunction in PatientsTreated with Paroxetine Tablets in Clinical Trials of MDD, OCD, PD, SAD, GAD,

and PTSDParoxetine Tablets Placebo

n (males) 1446%

1042%

Decreased Libido 6 to 15 0 to 5Ejaculatory Disturbance 13 to 28 0 to 2Impotence 2 to 9 0 to 3n (females) 1822

%1340

%Decreased Libido 0 to 9 0 to 2Orgasmic Disturbance 2 to 9 0 to 1

Paroxetine tablets treatment has been associated with several cases of priapism. Inthose cases with a known outcome, patients recovered without sequelae.

HallucinationsIn pooled clinical trials of paroxetine tablets, hallucinations were observed in 0.2% ofparoxetine tablets-treated patients compared to 0.1% of patients receiving placebo.

Less Common Adverse ReactionsThe following adverse reactions occurred during the clinical studies of paroxetine tabletsand are not included elsewhere in the labeling.Adverse reactions are categorized by body system and listed in order of decreasingfrequency according to the following definitions: Frequent adverse reactions are thoseoccurring on 1 or more occasions in at least 1/100 patients; infrequent adversereactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions arethose occurring in fewer than 1/1,000 patients.Body as a Whole: Infrequent: Allergic reaction, chills, face edema, malaise, neck pain;rare: Adrenergic syndrome, cellulitis, moniliasis, neck rigidity, pelvic pain, peritonitis,sepsis, ulcer.Cardiovascular System: Frequent: Hypertension, tachycardia; infrequent: Bradycardia,hematoma, hypotension, migraine, postural hypotension, syncope; rare: Anginapectoris, arrhythmia nodal, atrial 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, vascularheadache, ventricular extrasystoles.Digestive System: Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis,gastroenteritis, gingivitis, glossitis, increased salivation, abnormal liver function tests,rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea,bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impactions,fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinalobstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary glandenlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongueedema, tooth caries.Endocrine System: Rare: Diabetes mellitus, goiter, hyperthyroidism, hypothyroidism,thyroiditis.Hemic and Lymphatic Systems: Infrequent: Anemia, leukopenia, lymphadenopathy,purpura; rare: Abnormal erythrocytes, basophilia, bleeding time increased, eosinophilia,hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormallymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia,thrombocythemia, thrombocytopenia.Metabolic and Nutritional: Frequent: Weight gain; infrequent: Edema, peripheral edema,SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphataseincreased, bilirubinemia, BUN increased, creatinine phosphokinase increased,dehydration, gamma globulins increased, gout, hypercalcemia, hypercholesteremia,hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypoglycemia,

hypokalemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-proteinnitrogen (NPN) increased.Musculoskeletal System: Frequent: Arthralgia; infrequent: Arthritis, arthrosis;rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, tetany.Nervous System: Frequent: Emotional lability, vertigo; infrequent: Abnormal thinking,alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hostility, hypertonia, hypesthesia,hypokinesia, incoordination, lack of emotion, libido increased, manic reaction, neurosis,paralysis, paranoid reaction; rare: Abnormal gait, akinesia, antisocial reaction, aphasia,choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, diplopia, drugdependence, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsion,hyperalgesia, hysteria, manic-depressive reaction, meningitis, myelitis, neuralgia,neuropathy, nystagmus, peripheral neuritis, psychotic depression, psychosis, reflexesdecreased, reflexes increased, stupor, torticollis, trismus, withdrawal syndrome.Respiratory System: Infrequent: Asthma, bronchitis, dyspnea, epistaxis,hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups,lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration.Skin and Appendages: Frequent: Pruritus; infrequent: Acne, alopecia, contact dermatitis,dry skin, ecchymosis, eczema, herpes simplex, photosensitivity, urticaria;rare: Angioedema, erythema nodosum, erythema multiforme, exfoliative dermatitis,fungal dermatitis, furunculosis; herpes zoster, hirsutism, maculopapular rash,seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased,vesiculobullous rash.Special Senses: Frequent: Tinnitus; infrequent: Abnormality of accommodation,conjunctivitis, ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media;rare: Amblyopia, anisocoria, blepharitis, cataract, conjunctival edema, corneal ulcer,deafness, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness,otitis externa, parosmia, photophobia, ptosis, retinal hemorrhage, taste loss, visual fielddefect.Urogenital System: Infrequent: Amenorrhea, breast pain, cystitis, dysuria, hematuria,menorrhagia, nocturia, polyuria, pyuria, urinary incontinence, urinary retention, urinaryurgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement, endometrialdisorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain,leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts,uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis.

6.2 Postmarketing ExperienceThe following reactions have been identified during post approval use of paroxetinetablets. Because these reactions are reported voluntarily from a population of unknownsize, it is not always possible to reliably estimate their frequency or establish a causalrelationship to drug exposure.Acute pancreatitis, elevated liver function tests (the most severe cases were deaths dueto liver necrosis, and grossly elevated transaminases associated with severe liverdysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermalnecrolysis, 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; statusepilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis,eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS),ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolyticanemia, events related to impaired hematopoiesis (including aplastic anemia,pancytopenia, bone marrow aplasia, and agranulocytosis), vasculitic syndromes (suchas Henoch-Schönlein purpura), and premature births in pregnant women. There hasbeen a case report of severe hypotension when paroxetine tablets were added tochronic metoprolol treatment.

7 DRUG INTERACTIONSTable 9 presents clinically significant drug interactions with paroxetine tablets.

Table 9: Clinically Significant Drug Interactions with Paroxetine TabletsMonoamine 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 (2.5), Contraindications (4),Warnings and Precautions (5.2)].

Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid,methylene blue

Pimozide and ThioridazineClinical 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 DrugsClinical 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 dosageincreases. If serotonin syndrome occurs, considerdiscontinuation of paroxetine tablets and/or concomitantserotonergic drugs [see Warnings and Precautions (5.2)].

Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl,lithium, tramadol, tryptophan, buspirone, St. John’s Wort

Drugs that Interfere with Hemostasis (antiplatelet agents andanticoagulants)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 antiplateletagents and anticoagulants. For patients taking warfarin,carefully monitor the international normalized ratio [seeWarnings and Precautions (5.5)].

Examples aspirin, clopidogrel, heparin, warfarinDrugs Highly Bound to Plasma ProteinClinical Impact Paroxetine tablets are highly bound to plasma protein. The

concomitant use of paroxetine tablets with another drug that ishighly bound to plasma protein may increase freeconcentrations of paroxetine tablets or other tightly-bounddrugs in plasma.

Intervention Monitor for adverse reactions and reduce dosage of paroxetinetablets or other protein-bound drugs as warranted.

Examples warfarinDrugs Metabolized by CYP2D6Clinical Impact Paroxetine tablets are a CYP2D6 inhibitor [see Clinical

Pharmacology (12.3)]. The concomitant use of paroxetinetablets with a CYP2D6 substrate may increase the exposure ofthe CYP2D6 substrate.

Intervention Decrease the dosage of a CYP2D6 substrate if needed withconcomitant paroxetine tablets use. Conversely, an increase indosage of a CYP2D6 substrate may be needed if paroxetinetablets are discontinued.

Examples propafenone, flecainide, atomoxetine, desipramine,dextromethorphan, metoprolol, nebivolol, perphenazine,tolterodine, venlafaxine, risperidone.

TamoxifenClinical 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 noCYP2D6 inhibition [see Warnings and Precautions (5.11)].

Fosamprenavir/RitonavirClinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine

tablets significantly decreased plasma levels of paroxetinetablets.

Intervention Any dose adjustment should be guided by clinical effect(tolerability and efficacy).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category D[see Warnings and Precautions (5.4)]Epidemiological studies have shown that infants exposed to paroxetine in the firsttrimester of pregnancy have an increased risk of congenital malformations, particularlycardiovascular malformations. If paroxetine is used during pregnancy, or if the patientbecomes pregnant while taking paroxetine, advise the patient of the potential hazard tothe fetus.

Clinical ConsiderationsUnless the benefits of paroxetine to the mother justify continuing treatment,consideration should be given to either discontinuing paroxetine therapy or switching toanother antidepressant [see Warnings and Precautions (5.7)]. For

•

•

•

Other studies have found varying results as to whether there was an increased risk ofoverall, cardiovascular, or specific congenital malformations. A meta-analysis ofepidemiological data over a 16-year period (1992 to 2008) on first trimester paroxetineuse in pregnancy and congenital malformations included the above-noted studies inaddition to others (n = 17 studies that included overall malformations and n = 14studies that included cardiovascular malformations; n = 20 distinct studies). Whilesubject to limitations, this meta-analysis suggested an increased occurrence ofcardiovascular malformations (prevalence odds ratio [POR] 1.5; 95% confidence interval1.2 to 1.9) and overall malformations (POR 1.2; 95% confidence interval 1.1 to 1.4) withparoxetine use during the first trimester. It was not possible in this meta-analysis todetermine the extent to which the observed prevalence of cardiovascular malformationsmight have contributed to that of overall malformations, nor was it possible to determinewhether any specific types of cardiovascular malformations might have contributed tothe observed prevalence of all cardiovascular malformations.Unless the benefits of paroxetine to the mother justify continuing treatment,consideration should be given to either discontinuing paroxetine therapy or switching toanother antidepressant [see Warnings and Precautions (5.7)]. For women who intend tobecome pregnant or are in their first trimester of pregnancy, paroxetine should only beinitiated after consideration of the other available treatment options [see Warnings andPrecautions (5.4)].

Treatment of Pregnant Women During Their Third TrimesterNeonates exposed to SSRIs or serotonin and norepinephrine reuptake inhibitors(SNRIs), including paroxetine tablets, late in the third trimester have developedcomplications requiring prolonged hospitalization, respiratory support, and tube feeding.Such complications can arise immediately upon delivery. Reported clinical findings haveincluded respiratory distress, cyanosis, apnea, seizures, temperature instability, feedingdifficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor,jitteriness, irritability, and constant crying. These features are consistent with either adirect toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. Itshould be noted that, in some cases, the clinical picture is consistent with serotoninsyndrome [see Warnings and Precautions (5.2)].Exposure to SSRIs in late pregnancy may have an increased risk for persistentpulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 – 2 per 1,000 livebirths in the general population and is associated with substantial neonatal morbidity andmortality. In a retrospective case-control study of 377 women whose infants were bornwith PPHN and 836 women whose infants were born healthy, the risk for developingPPHN was approximately six-fold higher for infants exposed to SSRIs after the 20thweek of gestation compared to infants who had not been exposed to antidepressantsduring pregnancy.There have also been postmarketing reports of premature births in pregnant womenexposed to paroxetine or other SSRIs.When treating a pregnant woman with paroxetine during the third trimester, thephysician should carefully consider both the potential risks and benefits of treatment. Aprospective longitudinal study of 201 women with a history of major depression whowere euthymic at the beginning of pregnancy. The women who discontinuedantidepressant medication during pregnancy were more likely to experience a relapse ofmajor depression than women who continued antidepressant medication.

Animal Findings

A study based on Swedish national registry data demonstrated that infantsexposed to paroxetine during pregnancy (n = 815) had an increased risk ofcardiovascular malformations (2% risk in paroxetine-exposed infants) compared tothe entire registry population (1% risk), for an odds ratio (OR) of 1.8 (95%confidence interval 1.1 to 2.8). No increase in the risk of overall congenitalmalformations was seen in the paroxetine-exposed infants. The cardiacmalformations in the paroxetine-exposed infants were primarily ventricular septaldefects (VSDs) and atrial septal defects (ASDs). Septal defects range in severityfrom those that resolve spontaneously to those which require surgery.A separate retrospective cohort study from the United States (United Healthcaredata) evaluated 5,956 infants of mothers dispensed antidepressants during thefirst trimester (n = 815 for paroxetine). This study showed a trend towards anincreased risk for cardiovascular malformations for paroxetine (risk of 1.5%)compared to other antidepressants (risk of 1%), for an OR of 1.5 (95% confidenceinterval 0.8 to 2.9). Of the 12 paroxetine-exposed infants with cardiovascularmalformations, 9 had VSDs. This study also suggested an increased risk of overallmajor congenital malformations including cardiovascular defects for paroxetine (4%risk) compared to other (2% risk) antidepressants (OR 1.8; 95% confidence interval1.2 to 2.8).Two large case-control studies using separate databases, each with > 9,000 birthdefect cases and > 4,000 controls, found that maternal use of paroxetine duringthe first trimester of pregnancy was associated with a 2- to 3-fold increased risk ofright ventricular outflow tract obstructions. In one study the OR was 2.5 (95%confidence interval, 1.0 to 6.0, 7 exposed infants) and in the other study the ORwas 3.3 (95% confidence interval, 1.3 to 8.8, 6 exposed infants).

Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6mg/kg/day in rabbits administered during organogenesis. These doses areapproximately 6 (rat) and less than 2 (rabbit) times the maximum recommended humandose (MRHD – 75 mg) on an mg/m basis. These studies have revealed no evidence ofdevelopmental effects. However, in rats, there was an increase in pup deaths during thefirst 4 days of lactation when dosing occurred during the last trimester of gestation andcontinued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which isthan the MRHD on an mg/m basis. The no-effect dose for rat pup mortality was notdetermined. The cause of these deaths is not known.

8.3 Nursing MothersLike many other drugs, paroxetine is secreted in human milk. Because of the potentialfor serious adverse reactions in nursing infants from paroxetine tablets, a decisionshould be made whether to discontinue nursing infants or to discontinue the drug,taking into account the importance of the drug to the mother.

8.4 Pediatric UseThe safety and effectiveness of paroxetine tablets in pediatric patients have not beenestablished [see Box Warning]. Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine tablets-treated pediatric patients with MDD.Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients[see Boxed Warning, Warnings and Precautions (5.1)]. Decreased appetite and weightloss have been observed in association with the use of SSRIs.In placebo-controlled clinical trials conducted with pediatric patients, the followingadverse reactions were reported in at least 2% of pediatric patients treated withparoxetine tablets and occurred at a rate at least twice that for pediatric patientsreceiving placebo: emotional lability (including self-harm, suicidal thoughts, attemptedsuicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating,hyperkinesia, and agitation.Adverse reactions upon discontinuation of treatment with paroxetine tablets in thepediatric 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 (includingsuicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness,dizziness, nausea, and abdominal pain.

8.5 Geriatric UseIn premarketing clinical trials with paroxetine tablets, 17% of patients treated withparoxetine tablets (approximately 700) were 65 years of age or older. Pharmacokineticstudies revealed a decreased clearance in the elderly, and a lower starting dose isrecommended;, however, no overall differences in safety or effectiveness wereobserved between elderly and younger patients [see Dosage and Administration (2.4),Clinical Pharmacology (12.3)].SSRIs including paroxetine tablets, have been associated with cases of clinicallysignificant hyponatremia in elderly patients, who may be at greater risk for this adversereaction [see Warnings and Precautions (5.7)].

8.6 Renal and Hepatic ImpairmentIncreased plasma concentrations of paroxetine occur in patients with renal and hepaticimpairment. The initial dosage of paroxetine tablets should be reduced in patients withsevere renal impairment and in patients with severe hepatic impairment [see Dosage andAdministration (2.4), Clinical Pharmacology (12.3)].

10 OVERDOSAGEThe following have been reported with paroxetine tablet overdosage:

••

•

Gastrointestinal decontamination with activated charcoal should be considered inpatients who present early after a paroxetine overdose.Consider contacting a Poison Center (1-800-222-1222) or a medical toxicologist foradditional overdosage management recommendations.

11 DESCRIPTIONParoxetine tablets contain paroxetine hydrochloride, an SSRI. It is the hydrochloride saltof a phenylpiperidine compound identified chemically as (3S-trans)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-piperidine hydrochloride hemihydrate and has the

2

2

Seizures, which may be delayed, and altered mental status including coma.Cardiovascular toxicity, which may be delayed, including QRS and QTc intervalprolongation. Hypertension most commonly seen, but rarely can see hypotensionalone or with co-ingestants including alcohol.Serotonin syndrome (patients with a multiple drug overdosage with otherproserotonergic drugs may have a higher risk).

molecular formula of C H FNO •HCl•1/2H O. The molecular weight is 374.8 (329.4 asfree base). The structural formula of paroxetine hydrochloride is:

Paroxetine hydrochloride, USP (hemihydrate) is an odorless, white or almost whitecrystalline powder, having a melting point range of 129° to 131°C and a solubility of 5.4mg/mL in water.Paroxetine Tablets: Paroxetine tablets are for oral administration. Each film-coatedtablet contains 10 mg, 20 mg, 30 mg or 40 mg paroxetine equivalent to 11.38 mg,22.76 mg, 34.14 mg or 45.52 mg of paroxetine hydrochloride hemihydrate,respectively.Inactive ingredients consist of dibasic calcium phosphate dihydrate, FD&C Blue No. 1Aluminum Lake, hydroxypropyl cellulose, hypromellose, magnesium stearate,microcrystalline cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate,sodium starch glycolate (potato), titanium dioxide and triacetin.Paroxetine hydrochloride complies with USP Chromatographic Purity Test 1.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of ActionThe 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 serotonergicactivity in the central nervous system resulting from inhibition of neuronal reuptake ofserotonin (5-hydroxy-tryptamine, 5-HT).

12.2 PharmacodynamicsStudies at clinically relevant doses in humans have demonstrated that paroxetine blocksthe uptake of serotonin into human platelets. In vitro studies in animals also suggestthat paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake(SSRI) and has only very weak effects on norepinephrine and dopamine neuronalreuptake.

12.3 PharmacokineticsNonlinearity in pharmacokinetics is observed with increasing doses of paroxetine tablets.In a meta-analysis of paroxetine from 4 studies done in healthy volunteers followingmultiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lowerC or AUC than females.

AbsorptionParoxetine hydrochloride is completely absorbed after oral dosing of a solution of thehydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mgtablets daily for 30 days, steady-state paroxetine concentrations were achieved byapproximately 10 days for most subjects, although it may take substantially longer in anoccasional patient. At steady state, mean values of C , T , C , and T were 61.7ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21.0 hours (CV 32%),respectively. The steady-state C and C values were about 6 and 14 times whatwould be predicted from single-dose studies. Steady-state drug exposure based onAUC was about 8 times greater than would have been predicted from single-dosedata in these subjects. The excess accumulation is a consequence of the fact that 1 ofthe enzymes that metabolizes paroxetine is readily saturable.Paroxetine is equally bioavailable from the oral suspension and tablet.

Effect of Food

The effects of food on the bioavailability of paroxetine were studied in subjectsadministered a single dose with and without food. AUC was only slightly increased (6%)when drug was administered with food but the C was 29% greater, while the time toreach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours.

Distribution

19 20 3 2

max

max max min ½

max min

0-24

max

Paroxetine distributes throughout the body, including the CNS, with only 1% remainingin the plasma.Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations wouldnormally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding ofphenytoin or warfarin.

Elimination

Metabolism

The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30mg tablets daily for 30 days of paroxetine tablets.In steady-state dose proportionality studies involving elderly and nonelderly patients, atdoses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for thenonelderly, some nonlinearity was observed in both populations, again reflecting asaturable metabolic pathway. In comparison to C values after 20 mg daily, valuesafter 40 mg daily were only about 2 to 3 times greater than doubled.Paroxetine is extensively metabolized after oral administration. The principal metabolitesare polar and conjugated products of oxidation and methylation, which are readilycleared. Conjugates with glucuronic acid and sulfate predominate, and major metaboliteshave been isolated and identified. Data indicate that the metabolites have no more than1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolismof paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinicaldoses appears to account for the nonlinearity of paroxetine kinetics with increasingdose and increasing duration of treatment. The role of this enzyme in paroxetinemetabolism also suggests potential drug-drug interactions [see Drug Interactions (7)].Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who aredeficient in CYP2D6 (poor metabolizers).

Excretion

Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in theurine 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 asmetabolites and less than 1% as the parent compound over the 10-day post-dosingperiod.

Drug Interaction StudiesThere are clinically significant, known drug interactions between paroxetine and otherdrugs [see Drug Interactions (7)].

Figure 1. Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (logscale)

min

Figure 2. Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine

TheophyllineReports of elevated theophylline levels associated with paroxetine tablets treatment havebeen reported. While this interaction has not been formally studied, it is recommendedthat theophylline levels be monitored when these drugs are concurrently administered.

Drugs Metabolized by Cytochrome CYP3A4

An in vivo interaction study involving the coadministration under steady-state conditionsof paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetineon terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole,a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent thanparoxetine as an inhibitor of the metabolism of several substrates for this enzyme,including terfenadine, astemizole, cisapride, triazolam, and cyclosporine. Paroxetine’sextent of inhibition of CYP3A4 activity is not expected to be of clinical significance.

Specific PopulationsThe impact of specific populations on the pharmacokinetics of paroxetine are shown inFigure 3.The recommended starting dosage and maximum dosage of paroxetine tablets arereduced in elderly patients, patients with severe renal impairment, and patients withsevere hepatic impairment [see Dosage and Administration (2.4)].

Figure 3. Impact of Specific Population on the Pharmacokinetics of Paroxetine (logscale)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

CarcinogenesisTwo-year carcinogenicity studies were conducted in rodents given paroxetine in the dietat 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). These doses are upto 2.0 (mouse) and 3.2 (rat) times the MRHD of 75 mg on a mg/m basis. There was asignificantly greater number of male rats in the high-dose group with reticulum cellsarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups,respectively) and a significantly increased linear trend across dose groups for theoccurrence of lymphoreticular tumors in male rats. Female rats were not affected.Although there was a dose-related increase in the number of tumors in mice, there wasno drug-related increase in the number of mice with tumors. The relevance of thesefindings to humans is unknown.

MutagenesisParoxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assaysthat included the following: Bacterial mutation assay, mouse lymphoma mutation assay,unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo inmouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test inrats.

Impairment of FertilitySome clinical studies have shown that SSRIs (including paroxetine) may affect spermquality during SSRI treatment, which may affect fertility in some men.A reduced pregnancy rate was found in reproduction studies in rats at a dose ofparoxetine of 15 mg/kg/day, which is 2.4 times the MRHD of 75 mg on a mg/m basis.Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicitystudies for 2 to 52 weeks. These lesions consisted of vacuolation of epididymal tubularepithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of thetestes with arrested spermatogenesis at 25 mg/kg/day (8.2 and 4.1 times the MRHD of75 mg on a mg/m basis).

14 CLINICAL STUDIES

14.1 Major Depressive DisorderThe 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 to73). In these studies, paroxetine tablets were shown to be statistically significantly moreeffective than placebo in treating MDD by at least 2 of the following measures: HamiltonDepression Rating Scale (HDRS), the Hamilton depressed mood item, and the ClinicalGlobal Impression (CGI)-Severity of Illness. Paroxetine tablets were statisticallysignificantly 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 wasdemonstrated in a randomized withdrawal study. Patients who responded to paroxetinetablets (HDRS total score <8) during an initial 8-week open-label treatment phase werethen randomized to continue paroxetine tablets or placebo, for up to 1 year. Patientstreated with paroxetine tablets demonstrated a statistically significant lower relapse rateduring the withdrawal phase (15%) compared to those on placebo (39%). Effectivenesswas similar for male and female patients.

14.2 Obsessive Compulsive DisorderThe effectiveness of paroxetine tablets in the treatment of obsessive compulsivedisorder (OCD) was demonstrated in two 12-week multicenter placebo-controlledstudies 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. Study1 demonstrated that daily doses of paroxetine tablets 40 mg and 60 mg are effective inthe treatment of OCD. Patients receiving doses of paroxetine tablets 40 mg and 60 mgexperienced a mean reduction of approximately 6 and 7 points, respectively, on theYBOCS 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. Study2 was a flexible-dose study comparing paroxetine tablets 20 mg to 60 mg daily withclomipramine 25 mg to 250 mg daily or placebo). In this study, patients receivingparoxetine tablets experienced a mean reduction of approximately 7 points on theYBOCS total score, which was statistically significantly greater than the mean reductionof approximately 4 points in placebo-treated patients.

2

2

2

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

Table 10: Outcome Classification (%) on CGI-Global Improvement Item forCompleters in Study 1 in Patients with OCD

OutcomeClassification

Placebo(n = 74)

%

ParoxetineTablets 20

mg(n = 75)

%

ParoxetineTablets 40

mg(n = 66)

%

ParoxetineTablets 60

mg(n = 66)

%Worse 14 7 7 3No Change 44 35 22 19Minimally Improved 24 33 29 34Much Improved 11 18 22 24Very Much Improved 7 7 20 20

Subgroup analyses did not indicate that there were any differences in treatmentoutcomes as a function of age or gender.The long-term efficacy of paroxetine tablets for the treatment of OCD was established ina long-term extension to Study 1. Patients who responded to paroxetine tablets duringthe 3-month double-blind phase and a 6-month extension on open-label paroxetinetablets 20 mg to 60 mg daily were randomized to either paroxetine tablets or placebo ina 6-month double-blind relapse prevention phase. Patients randomized to paroxetinetablets were statistically significantly less likely to relapse than placebo-treated patients.

14.3 Panic DisorderThe effectiveness of paroxetine tablets in the treatment of panic disorder (PD) wasdemonstrated in three 10- to 12-week multicenter, placebo-controlled studies of adultoutpatients (Studies 1, 2, and 3). Patients had PD (DSM-IIIR), with or withoutagoraphobia. In these studies, paroxetine tablets were shown to be statisticallysignificantly more effective than placebo in treating PD by at least 2 out of 3 measuresof 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 ofparoxetine tablets 10 mg, 20 mg, or 40 mg daily or placebo. A statistically significantdifference 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 panicattacks, compared to 44% of placebo-treated patients.Study 2 was a 12-week flexible-dose study comparing paroxetine tablets 10 mg to 60mg daily and placebo. At endpoint, 51% of paroxetine tablets-treated patients were freeof panic attacks compared to 32% of placebo-treated patients.Study 3 was a 12-week flexible-dose study comparing paroxetine tablets 10 mg to 60mg daily to placebo in patients concurrently receiving standardized cognitive behavioraltherapy. At endpoint, 33% of the paroxetine tablets-treated patients showed a reductionto 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 wasapproximately 40 mg daily.Long-term efficacy of paroxetine tablets in PD was demonstrated in an extension toStudy 1. Patients who responded to paroxetine tablets during the 10-week double-blindphase and during a 3-month double-blind extension phase were randomized to eitherparoxetine tablets 10 mg, 20 mg, or 40 mg daily or placebo in a 3-month double-blindrelapse prevention phase. Patients randomized to paroxetine tablets were statisticallysignificantly less likely to relapse than placebo-treated patients.Subgroup analyses did not indicate that there were any differences in treatmentoutcomes as a function of age or gender.

14.4 Social Anxiety DisorderThe 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 ofparoxetine tablets compared to placebo was evaluated on the basis of (1) the proportionof 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 theLiebowitz Social Anxiety Scale (LSAS).Studies 1 and 2 were flexible-dose studies comparing paroxetine tablets 20 mg to 50 mgdaily and placebo. Paroxetine tablets demonstrated statistically significant superiorityover placebo on both the CGI Improvement responder criterion and the Liebowitz SocialAnxiety Scale (LSAS). In Study 1, for patients who completed to week 12, 69% ofparoxetine tablets-treated patients compared to 29% of placebo-treated patients wereCGI Improvement responders. In Study 2, CGI Improvement responders were 77% and42% 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 significantlysuperior to placebo on both the LSAS Total Score and the CGI Improvement respondercriterion; there were trends for superiority over placebo for the paroxetine tablets 40mg and 60 mg daily dose groups. There was no indication in this study of any additionalbenefit for doses higher than 20 mg daily.Subgroup analyses generally did not indicate differences in treatment outcomes as afunction of age, race, or gender.

14.5 Generalized Anxiety DisorderThe effectiveness of paroxetine tablets in the treatment of generalized anxiety disorder(GAD) was demonstrated in two 8-week, multicenter, placebo-controlled studies (Studies1 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 40mg daily with placebo. Doses of paroxetine tablets 20 mg or 40 mg were bothdemonstrated to be statistically significantly superior to placebo on the Hamilton RatingScale for Anxiety (HAM-A) total score.There was not sufficient evidence in this study to suggest a greater benefit for theparoxetine 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 dailyand placebo. Paroxetine tablets demonstrated statistically significant superiority overplacebo 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 dailyto placebo, did not demonstrate statistically significant superiority of paroxetine tabletsover placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, the primaryoutcome.Subgroup analyses did not indicate differences in treatment outcomes as a function ofrace or gender. There were insufficient elderly patients to conduct subgroup analyseson the basis of age.In a long-term trial, 566 patients meeting DSM-IV criteria for GAD, who had respondedduring a single-blind, 8-week acute treatment phase with paroxetine tablets 20 mg to 50mg daily, were randomized to continuation of paroxetine tablets at their same dose, orto 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 theCGI-Severity of Illness scale, to a score of ≤ 3. Relapse during the double-blind phasewas defined as an increase of ≥ 2 points compared to baseline on the CGI-Severity ofIllness scale to a score of ≥ 4, or withdrawal due to lack of efficacy. Patients continuingto receive paroxetine tablets experienced a statistically significantly lower relapse rateover the subsequent 24 weeks compared to those receiving placebo.

14.6 Posttraumatic Stress DisorderThe effectiveness of paroxetine tablets in the treatment of Posttraumatic StressDisorder (PTSD) was demonstrated in two 12-week, multicenter, placebo-controlledstudies (Studies 1 and 2) of adult outpatients who met DSM-IV criteria for PTSD. Themean duration of PTSD symptoms for the 2 studies combined was 13 years (rangingfrom 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 GlobalImpression-Global Improvement Scale (CGI-I). The CAPS-2 is a multi-item instrument thatmeasures 3 aspects of PTSD with the following symptom clusters:Reexperiencing/intrusion, avoidance/numbing and hyperarousal. The 2 primaryoutcomes for each trial were (1) change from baseline to endpoint on the CAPS-2 totalscore (17 items), and (2) proportion of responders on the CGI-I, where responderswere defined as patients having a score of 1 (very much improved) or 2 (muchimproved).Study 1 was a 12-week study comparing fixed doses of paroxetine tablets 20 mg or 40mg daily to placebo. Doses of paroxetine tablets 20 mg and 40 mg were demonstratedto 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 sufficientevidence in this study to suggest a greater benefit for the 40 mg daily dose compared tothe 20 mg daily dose.Study 2 was a 12-week flexible-dose study comparing paroxetine tablets 20 mg to 50mg daily to placebo. Paroxetine tablets were demonstrated to be significantly superior toplacebo on change from baseline for the CAPS-2 total score and on proportion ofresponders on the CGI-I.A third study, a flexible-dose study comparing paroxetine tablets 20 mg to 50 mg dailyto placebo, demonstrated paroxetine tablets to be statistically significantly superior toplacebo on change from baseline for CAPS-2 total score, but not on proportion ofresponders on the CGI-I.The majority of patients in these trials were women (68% women: 377 out of 551subjects 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 werenon-Caucasian to conduct subgroup analyses on the basis of age or race, respectively.

16 HOW SUPPLIED/STORAGE AND HANDLINGParoxetine Tablets, USP are available containing paroxetine hydrochloride, USP(hemihydrate) equivalent to 10 mg, 20 mg, 30 mg or 40 mg of paroxetine.The 10 mg tablets are blue, film-coated, modified capsule-shaped, scored tabletsdebossed with M on one side of the tablet and N to the left of the score and 1 to theright of the score on the other side. They are available as follows:NDC 0378-7001-93bottles of 30 tabletsNDC 0378-7001-10bottles of 1000 tabletsThe 20 mg tablets are blue, film-coated, modified capsule-shaped, scored tabletsdebossed with M on one side of the tablet and N to the left of the score and 2 to theright of the score on the other side. They are available as follows:NDC 0378-7002-93bottles of 30 tabletsNDC 0378-7002-10bottles of 1000 tabletsThe 30 mg tablets are blue, film-coated, round, unscored tablets debossed with M overN3 on one side of the tablet and blank on the other side. They are available as follows:NDC 0378-7003-93bottles of 30 tabletsNDC 0378-7003-10bottles of 1000 tabletsThe 40 mg tablets are blue, film-coated, round, unscored tablets debossed with M overN4 on one side of the tablet and blank on the other side. They are available as follows:NDC 0378-7004-93bottles of 30 tabletsNDC 0378-7004-10bottles of 1000 tabletsStore at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Dispense in a tight, light-resistant container as defined in the USP using a child-resistantclosure.PHARMACIST: Dispense a Medication Guide with each prescription.

17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide).Suicidal Thoughts and Behaviors: Advise patients and caregivers to look for theemergence of suicidality, especially early during treatment and when the dosage isadjusted up or down, and instruct them to report such symptoms to the healthcareprovider [see Boxed Warning and Warnings and Precautions (5.1)].Serotonin Syndrome: Caution patients about the risk of serotonin syndrome,particularly with the concomitant use of paroxetine tablets with other serotonergicdrugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impairmetabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatricdisorders and also others, such as linezolid). Instruct patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms ofserotonin syndrome [see Warnings and Precautions (5.2), Drug Interactions (7)].Concomitant Medications: Advise patients to inform their physician if they are taking,or plan to take, any prescription or over-the-counter drugs, since there is a potential fordrug-drug interactions [see Warning and Precautions (5.3), Drug Interactions (7)].Increased Risk of Bleeding: Inform patients about the concomitant use ofparoxetine tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or otheranticoagulants because the combined use has been associated with an increased risk ofbleeding. Advise patients to inform their health care providers if they are taking orplanning to take any prescription or over-the counter medications that increase the riskof bleeding [see Warnings and Precautions (5.5)].Activation of Mania/Hypomania: Advise patients and their caregivers to observe forsigns of activation of mania/hypomania and instruct them to report such symptoms tothe healthcare provider [see Warnings and Precautions (5.6)].

Discontinuation Syndrome: Advise patients not to abruptly discontinue paroxetinetablets and to discuss any tapering regimen with their healthcare provider. Informpatients that adverse reactions can occur when paroxetine tablets are discontinued [seeWarnings and Precautions (5.7)].Sexual Dysfunction: Advise patients that use of paroxetine tablets may causesymptoms of sexual dysfunction in both male and female patients. Inform patients thatthey should discuss any changes in sexual function and potential managementstrategies with their healthcare provider [see Warnings and Precautions (5.13)].Allergic Reactions: Advise patients to notify their healthcare provider if they developan allergic reaction such as rash, hives, swelling, or difficulty breathing [see AdverseReactions (6.1, 6.2)].Embryo-Fetal Toxicity: Advise women of the potential risk to the fetus [see Warningsand Precautions (5.4), Use in Specific Populations (8.1)]. Advise patients to notify theirhealthcare provider if they become pregnant or intend to become pregnant duringtherapy because of the risk to the fetus.Nursing: Advise women to notify their healthcare provider if they are breastfeeding aninfant [see Use in Specific Populations (8.3)].

Medication Guide

Paroxetine Tablets, USP(pa roxʹ e teen)What is the most important information I should know about paroxetinetablets? Paroxetine tablets can cause serious side effects, including:

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Call your healthcare provider or get emergency medical help right away ifyou have any of the following symptoms, especially if they are new, worse,or worry you:

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What are paroxetine tablets? Paroxetine tablets are a prescription medicine used in adults to treat:

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Do not take paroxetine tablets if you:

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Increased risk of suicidal thoughts or actions. Paroxetine tablets and otherantidepressant medicines may increase suicidal thoughts and actions in somepeople 24 years of age and younger, especially within the first few months oftreatment or when the dose is changed.Paroxetine tablets are not foruse in children.

o Depression or other mental illnesses are the most important causesof 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 veryimportant when an antidepressant medicine is started or when the dose ischanged.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 yourhealthcare provider between visits as needed, especially if you have concernsabout symptoms.

attempts to commit suicideacting aggressive or violentnew or worse depressionfeeling agitated, restless, angry, orirritablean increase in activity and talking morethan what is normal for you

acting on dangerous impulsesthoughts about suicide or dyingnew or worse anxiety or panic attackstrouble sleepingother unusual changes in behavior ormood

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)

take a monoamine oxidase inhibitor (MAOI)have stopped taking an MAOI in the last 14 daysare being treated with the antibiotic linezolid or the intravenous methylene blueare taking pimozide

••

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI orone 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 treatmentwith paroxetine tablets.Before taking paroxetine tablets, tell your healthcare provider about all yourmedical conditions, including if you:

•••••••••

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Tell your healthcare provider about all the medicines you take, includingprescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine tablets and some other medicines may affect each other causing possibleserious side effects. Paroxetine tablets may affect the way other medicines work andother medicines may affect the way paroxetine tablets work. Especially tell your healthcare provider if you take:

••••••••••

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Ask your healthcare provider if you are not sure if you are taking any of thesemedicines. Your healthcare provider can tell you if it is safe to take paroxetine tabletswith your other medicines. Do not start or stop any other medicines during treatment with paroxetine tabletswithout talking to your healthcare provider first. Stopping paroxetine tablets suddenlymay cause you to have serious side effects. See, “What are the possible sideeffects of paroxetine tablets?” Know the medicines you take. Keep a list of them to show to your healthcare providerand pharmacist when you get a new medicine.How should I take paroxetine tablets?

•

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What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including:

are taking thioridazineare allergic to paroxetine or any of the ingredients in paroxetine tablets. See theend of this Medication Guide for a complete list of ingredients in paroxetine tablets.

have heart problemshave or had bleeding problemshave, or have a family history of, bipolar disorder, mania or hypomaniahave or had seizures or convulsionshave glaucoma (high pressure in the eye)have low sodium levels in your bloodhave bone problemshave kidney or liver problemsare pregnant or plan to become pregnant. Paroxetine tablets may harm yourunborn baby. Talk to your healthcare provider about the risks to your unborn babyif you take paroxetine tablets during pregnancy. Tell your healthcare provider rightaway if you become pregnant or think you are pregnant during treatment withparoxetine 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 duringtreatment with paroxetine tablets.

medicines used to treat migraine headaches called triptanstricyclic antidepressantsfentanyllithiumtramadoltryptophanbuspironeamphetaminesSt. John’s Wortmedicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarindiureticstamoxifenmedicines used to treat mood, anxiety, psychotic, or thought disorders, includingselective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptakeinhibitors (SNRIs)

Take paroxetine tablets exactly as prescribed. Your healthcare provider may needto 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.

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See, “What is the most important information I should know aboutparoxetine tablets?”Serotonin syndrome. A potentially life-threatening problem called serotoninsyndrome can happen when you take paroxetine tablets with certain othermedicines. See, “Who should not take paroxetine tablets?” Call your healthcareprovider or go to the nearest hospital emergency room right away if youhave any of the following signs and symptoms of serotonin syndrome:

agitationseeing or hearing things that are notreal (hallucinations)confusioncomafast heart beatchanges in blood pressuredizziness

sweatingflushinghigh body temperature (hyperthermia)shaking (tremors), stiff muscles, ormuscle twitchingloss of coordinationseizuresnausea, vomiting, diarrhea

Eye problems (angle-closure glaucoma). Paroxetine tablets may cause a typeof eye problem called angle-closure glaucoma in people with certain other eyeconditions. You may want to undergo an eye examination to see if you are at riskand receive preventative treatment if you are. Call your healthcare provider if youhave eye pain, changes in your vision, or swelling or redness in or around the eye.Medicine interactions. Taking paroxetine tablets with certain other medicinesincluding thioridazine and pimozide may increase the risk of developing a seriousheart problem called QT prolongation.Seizures (convulsions).Manic episodes. Manic episodes may happen in people with bipolar disorder whotake paroxetine tablets. Symptoms may include:

greatly increased energyracing thoughtsunusually grand ideastalking more or faster than usual

severe problems sleepingreckless behaviorexcessive happiness or irritability

Discontinuation syndrome. Suddenly stopping paroxetine tablets may causeyou to have serious side effects. Your healthcare provider may want to decreaseyour dose slowly. Symptoms may include:

nauseasweatingchanges in your moodirritability and agitationdizziness

electric shock feeling(paresthesia)tremoranxietyconfusionheadache

tirednessproblems sleepinghypomaniaringing in your ears(tinnitus)seizures

Low sodium levels in your blood (hyponatremia). Low sodium levels in yourblood that may be serious and may cause death, can happen during treatment withparoxetine tablets. Elderly people and people who take certain medicines may be ata greater risk for developing low sodium levels in your blood. Signs and symptomsmay include:

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headachedifficulty concentratingmemory changesconfusionweakness and unsteadiness on your feet which can lead to falls In more severe or more sudden cases, signs and symptoms include:

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seeing or hearing things that are not real (hallucinations)faintingseizurescomastopping breathing (respiratory arrest)

Abnormal bleeding. Taking paroxetine tablets with aspirin, NSAIDs, or bloodthinners may increase this risk. Tell your healthcare provider about any unusualbleeding or bruising.Bone fractures.Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors(SSRIs), including paroxetine tablets, may cause sexual problems.Symptoms in males may include:

The most common side effects of paroxetine tablets include:

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These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report sideeffects to FDA at 1-800-FDA-1088.How should I store paroxetine tablets?

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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 aMedication Guide. Do not take paroxetine tablets for a condition for which they were notprescribed. Do not give paroxetine tablets to other people, even if they have the samesymptoms that you have. They may harm them. You may ask your healthcare provideror pharmacist for information about paroxetine tablets that is written for healthcareprofessionals.What are the ingredients in paroxetine tablets? Active ingredient: paroxetine hydrochloride Inactive ingredients: Tablets: dibasic calcium phosphate dihydrate, FD&C Blue No. 1 Aluminum Lake,hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose,polydextrose, polyethylene glycol, sodium lauryl sulfate, sodium starch glycolate(potato), titanium dioxide and triacetin.Manufactured for: Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A.Manufactured by: ALPHAPHARM PTY LTD, 15 Garnet Street, Carole Park QLD 4300Australia The brands listed are trademarks of their respective owners. For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX).

This Medication Guide has been approved by the U.S. Food and Drug Administration.Manufactured for:Mylan Pharmaceuticals Inc.Morgantown, WV 26505 U.S.A.Manufactured by: ALPHAPHARM PTY LTD15 Garnet StreetCarole Park QLD 4300AustraliaRevised: 10/2021ALP:PXTT:R12mh/ ALP:MG:PXTT:R5mh(2848/5)

PRINCIPAL DISPLAY PANEL – 10 mgNDC 0378-7001-93

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Delayed ejaculation or inability to have an ejaculationDecreased sex driveProblems getting or keeping an erection

Symptoms in females may include:

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Decreased sex driveDelayed orgasm or inability to have an orgasm

Talk to your healthcare provider if you develop any changes in your sexual functionor if you have any questions or concerns about sexual problems during treatmentwith paroxetine tablets. There may be treatments your healthcare provider cansuggest.

male and female sexual functionproblemsconstipationdiarrheadry mouthproblems sleepingnervousnesssweatingyawning

weakness (asthenia)decreased appetitedizzinessinfectionnauseasleepinessshaking (tremor)

Store paroxetine tablets between 20° to 25°C (68° to 77°F).

NDC 0378-7001-93Paroxetine Tablets, USP 10 mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only 30 TabletsEach film-coated tablet contains paroxetine hydrochloride, USP (hemihydrate) equivalent to 10 mg of paroxetine.Dispense in a tight, light-resistantcontainer as defined in the USPusing a child-resistant closure.Keep container tightly closed.Keep this and all medication out of the reach of children.Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Usual Dosage: See accompanyingprescribing information.Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Made in AustraliaMylan.comRALP7001H32833/2

PRINCIPAL DISPLAY PANEL – 20 mgNDC 0378-7002-93Paroxetine Tablets, USP 20 mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only 30 TabletsEach film-coated tablet contains paroxetine hydrochloride, USP (hemihydrate) equivalent to 20 mg of paroxetine.Dispense in a tight, light-resistantcontainer as defined in the USPusing a child-resistant closure.Keep container tightly closed.Keep this and all medication out of the reach of children.Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room

Temperature.]Usual Dosage: See accompanyingprescribing information.Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Made in AustraliaMylan.comRALP7002H32835/2

PRINCIPAL DISPLAY PANEL – 30 mgNDC 0378-7003-93Paroxetine Tablets, USP 30 mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only 30 TabletsEach film-coated tablet contains paroxetine hydrochloride, USP (hemihydrate) equivalent to 30 mg of paroxetine.Dispense in a tight, light-resistantcontainer as defined in the USPusing a child-resistant closure.Keep container tightly closed.Keep this and all medication out of the reach of children.Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Usual Dosage: See accompanyingprescribing information.Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Made in AustraliaMylan.comRALP7003H32837/2

PRINCIPAL DISPLAY PANEL – 40 mgNDC 0378-7004-93Paroxetine Tablets, USP 40 mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only 30 TabletsEach film-coated tablet contains paroxetine hydrochloride, USP (hemihydrate) equivalent to 40 mg of paroxetine.Dispense in a tight, light-resistantcontainer as defined in the USPusing a child-resistant closure.Keep container tightly closed.Keep this and all medication out of the reach of children.Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Usual Dosage: See accompanyingprescribing information.Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.Made in AustraliaMylan.comRALP7004H32839/2

PAROXETINE paroxetine hydrochloride hemihydrate tablet, film coated

Product Information

Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-7001

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of

Strength Strength

PAROXETINE HYDROCHLORIDE HEMIHYDRATE (UNII: X2ELS050D8) (PAROXETINE -UNII:41VRH5220H) PAROXETINE 10 mg

Inactive IngredientsIngredient Name Strength

DIBASIC CALCIUM PHOSPHATE DIHYDRATE (UNII: O7TSZ97GEP) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) HYDROXYPROPYL CELLULOSE, UNSPECIFIED (UNII: 9XZ8H6N6OH) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) POLYDEXTROSE (UNII: VH2XOU12IE) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) SODIUM LAURYL SULFATE (UNII: 368GB5141J) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) TRIACETIN (UNII: XHX3C3X673)

Product CharacteristicsColor BLUE Score 2 piecesShape OVAL (modified capsule-shaped) Size 9mmFlavor Imprint Code M;N;1Contains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0378-

7001-9330 in 1 BOTTLE, PLASTIC; Type 0: Not a CombinationProduct 03/24/2008

2 NDC:0378-7001-10

1000 in 1 BOTTLE, PLASTIC; Type 0: Not aCombination Product 03/24/2008

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

ANDA ANDA078902 03/24/2008

PAROXETINE paroxetine hydrochloride hemihydrate tablet, film coated

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-7002

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of

Strength Strength

PAROXETINE HYDROCHLORIDE HEMIHYDRATE (UNII: X2ELS050D8) (PAROXETINE -UNII:41VRH5220H) PAROXETINE 20 mg

Inactive IngredientsIngredient Name Strength

DIBASIC CALCIUM PHOSPHATE DIHYDRATE (UNII: O7TSZ97GEP) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) HYDROXYPROPYL CELLULOSE, UNSPECIFIED (UNII: 9XZ8H6N6OH) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) POLYDEXTROSE (UNII: VH2XOU12IE) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) SODIUM LAURYL SULFATE (UNII: 368GB5141J) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)

TITANIUM DIOXIDE (UNII: 15FIX9V2JP) TRIACETIN (UNII: XHX3C3X673)

Product CharacteristicsColor BLUE Score 2 piecesShape OVAL (modified capsule-shaped) Size 11mmFlavor Imprint Code M;N;2Contains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0378-

7002-9330 in 1 BOTTLE, PLASTIC; Type 0: Not a CombinationProduct 03/24/2008

2 NDC:0378-7002-10

1000 in 1 BOTTLE, PLASTIC; Type 0: Not aCombination Product 03/24/2008

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

ANDA ANDA078902 03/24/2008

PAROXETINE paroxetine hydrochloride hemihydrate tablet, film coated

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-7003

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of

Strength Strength

PAROXETINE HYDROCHLORIDE HEMIHYDRATE (UNII: X2ELS050D8) (PAROXETINE -UNII:41VRH5220H) PAROXETINE 30 mg

Inactive IngredientsIngredient Name Strength

DIBASIC CALCIUM PHOSPHATE DIHYDRATE (UNII: O7TSZ97GEP) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) HYDROXYPROPYL CELLULOSE, UNSPECIFIED (UNII: 9XZ8H6N6OH) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) POLYDEXTROSE (UNII: VH2XOU12IE) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) SODIUM LAURYL SULFATE (UNII: 368GB5141J) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) TRIACETIN (UNII: XHX3C3X673)

Product CharacteristicsColor BLUE Score no scoreShape ROUND Size 9mmFlavor Imprint Code M;N3Contains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0378-

7003-9330 in 1 BOTTLE, PLASTIC; Type 0: Not a CombinationProduct 03/24/2008

2 NDC:0378-7003-10

1000 in 1 BOTTLE, PLASTIC; Type 0: Not aCombination Product 03/24/2008

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

Mylan Pharmaceuticals Inc.

ANDA ANDA078902 03/24/2008

PAROXETINE paroxetine hydrochloride hemihydrate tablet, film coated

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-7004

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of

Strength Strength

PAROXETINE HYDROCHLORIDE HEMIHYDRATE (UNII: X2ELS050D8) (PAROXETINE -UNII:41VRH5220H) PAROXETINE 40 mg

Inactive IngredientsIngredient Name Strength

DIBASIC CALCIUM PHOSPHATE DIHYDRATE (UNII: O7TSZ97GEP) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) HYDROXYPROPYL CELLULOSE, UNSPECIFIED (UNII: 9XZ8H6N6OH) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) POLYDEXTROSE (UNII: VH2XOU12IE) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) SODIUM LAURYL SULFATE (UNII: 368GB5141J) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) TRIACETIN (UNII: XHX3C3X673)

Product CharacteristicsColor BLUE Score no scoreShape ROUND Size 10mmFlavor Imprint Code M;N4Contains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0378-

7004-9330 in 1 BOTTLE, PLASTIC; Type 0: Not a CombinationProduct 03/24/2008

2 NDC:0378-7004-10

1000 in 1 BOTTLE, PLASTIC; Type 0: Not aCombination Product 03/24/2008

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

ANDA ANDA078902 03/24/2008

Labeler - Mylan Pharmaceuticals Inc. (059295980)

Revised: 10/2021