Sertraline HCl

1 INDICATIONS AND USAGE Sertraline Hydrochloride (HCl) Capsules is indicated for the treatment of the following [see Clinical Studies ( 14 )] : Major depressive disorder (MDD) in adults Obsessive-compulsive disorder (OCD) in adults and pediatric patients 6 years and older Sertraline Hydrochloride (HCl) Capsules is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of ( 1 ): Major depressive disorder (MDD) in adults Obsessive-compulsive disorder (OCD) in adults and pediatric patients 6 years and older

2 DOSAGE AND ADMINISTRATION Do not initiate treatment with Sertraline HCl Capsules. Use another sertraline HCl product for initial dosage, titration, and dosages below 150 mg once daily ( 2.1 ) Recommended dosage is 150 mg or 200 mg once daily ( 2.1 ) Maximum recommended dosage is 200 mg once daily ( 2.1 ) Swallow capsules whole. Do not open, crush, or chew ( 2.2 ) When discontinuing Sertraline HCl Capsules, reduce dose gradually whenever possible. Gradual dosage reduction will require use of another sertraline HCl product ( 2.5 , 5.5 ) 2.1 Dosing in Patients with MDD and OCD Do not initiate treatment with Sertraline HCl Capsules because the only available dose strengths are 150 mg and 200 mg. Use another sertraline HCl product for initial dosage, titration, and dosages below 150 mg once daily. Refer to Prescribing Information of the other sertraline HCl products for the recommended dosage for those products. Sertraline HCl Capsules can be initiated in patients receiving 100 mg or 125 mg of sertraline HCl for at least one week. The recommended dosage of Sertraline HCl Capsules is 150 mg or 200 mg once daily. The maximum recommended dosage is 200 mg once daily. 2.2 Administration Instructions Administer Sertraline HCl Capsules orally. Swallow capsules whole; do not open, crush, or chew. 2.3 Screen for Bipolar Disorder Prior to Starting Sertraline HCl Capsules Prior to initiating treatment with Sertraline HCl Capsules or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.4 )] . 2.4 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of Sertraline HCl Capsules. In addition, at least 14 days must elapse after stopping Sertraline HCl Capsules before starting an MAOI antidepressant [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . 2.5 Discontinuation of Treatment with Sertraline HCl Capsules Adverse reactions may occur upon discontinuation of Sertraline HCl Capsules [see Warnings and Precautions ( 5.5 )] . Gradually reduce the dosage rather than stopping Sertraline HCl Capsules abruptly whenever possible. Given that dosage strengths lower than 150 mg of Sertraline HCl Capsules are not available, gradual dosage reduction will require the use of another sertraline HCl product.

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue Sertraline HCl Capsules and serotonergic agents and initiate supportive treatment ( 4 , 5.2 , 7.1 ) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.3 ) Activation of Mania or Hypomania: Screen patients for bipolar disorder ( 5.4 ) Discontinuation Syndrome: When discontinuing Sertraline HCl Capsules, reduce dosage gradually whenever possible, and monitor for discontinuation symptoms. Gradual reduction will require use of another sertraline HCl product ( 5.5 ) Seizures: Use with caution in patients with seizure disorders ( 5.6 ) Angle Closure Glaucoma: Avoid use of antidepressants, including Sertraline HCl Capsules, in patients with untreated anatomically narrow angles ( 5.7 ) QTc Prolongation: Sertraline HCl Capsules should be used with caution in patients with risk factors for QTc prolongation ( 5.10 ) Sexual Dysfunction: Sertraline HCl Capsules may cause symptoms of sexual dysfunction ( 5.12 ) 5.1 Suicidal Thoughts and Behaviors in Adolescent and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,500 pediatric 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 among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts or Behavior in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥65 years old 6 fewer 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 in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing Sertraline HCl Capsules, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome SSRIs, including Sertraline HCl Capsules, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.…

4 CONTRAINDICATIONS Sertraline HCl Capsules are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 )] . Taking pimozide [see Drug Interactions ( 7.1 )] . With known hypersensitivity to sertraline or the excipients in Sertraline HCl Capsules (e.g., anaphylaxis, angioedema) [see Adverse Reactions ( 6.1 , 6.2 )] . Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ( 4 , 7.1 ) Concomitant use of pimozide ( 4 , 7.1 ) Known hypersensitivity to sertraline or excipients ( 4 )

7 DRUG INTERACTIONS Protein-bound drugs: Monitor for adverse reactions and reduce dosage of Sertraline HCl Capsules or other protein-bound drugs (e.g., warfarin) as warranted ( 7.1 , 12.3 ) CYP2D6 substrates: Reduce dosage of drugs metabolized by CYP2D6 ( 7.1 , 12.3 ) 7.1 Clinically Significant Drug Interactions Table 4 includes clinically significant drug interactions with Sertraline HCl Capsules [see Clinical Pharmacology ( 12.3 )] . Table 4. Clinically-Significant Drug Interactions with Sertraline HCl Capsules Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of SSRIs, including Sertraline HCl Capsules, and MAOIs increases the risk of serotonin syndrome. Intervention: Sertraline HCl Capsules is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.4 ), Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Pimozide Clinical Impact: Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention: Concomitant use of pimozide and Sertraline HCl Capsules is contraindicated [see Contraindications ( 4 )] . Other Serotonergic Drugs Clinical Impact: Concomitant use of Sertraline HCl Capsules with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Sertraline HCl Capsules and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] . Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with Sertraline HCl Capsules may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of Sertraline HCl Capsules and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions ( 5.3 )] . Drugs Highly Bound to Plasma Protein Clinical Impact: Sertraline is highly bound to plasma protein. The concomitant use of Sertraline HCl Capsules with another drug that is highly bound to plasma protein may increase free concentrations of sertraline or other tightly-bound drugs in plasma [see Clinical Pharmacology ( 12.3 )] . Intervention: Monitor for adverse reactions and reduce dosage of Sertraline HCl Capsules or other protein-bound drugs as warranted. Drugs Metabolized by CYP2D6 Clinical Impact: Sertraline HCl Capsules are a CYP2D6 inhibitor [see Clinical Pharmacology ( 12.3 )] . The concomitant use of Sertraline HCl Capsules with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant Sertraline HCl Capsules use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Sertraline HCl Capsules are discontinued. Phenytoin Clinical Impact: Phenytoin is a narrow therapeutic index drug. Sertraline HCl Capsules may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating Sertraline HCl Capsules. Reduce phenytoin dosage if needed. Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of Sertraline HCl Capsules with other drugs which prolong the QTc interval [see Warnings and Precautions ( 5.10 ), Clinical Pharmacology ( 12.2 )] . Intervention: Pimozide is contraindicated for use with Sertraline HCl Capsules. Avoid the concomitant use of drugs known to pro…

6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribing information: Hypersensitivity reactions to sertraline or excipients of Sertraline HCl Capsules [see Contraindications ( 4 )] Suicidal Thoughts and Behaviors in Adolescent and Young Adults [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 )] Increased Risk of Bleeding [see Warnings and Precautions ( 5.3 )] Activation of Mania or Hypomania [see Warnings and Precautions ( 5.4 )] Discontinuation Syndrome [see Warnings and Precautions ( 5.5 )] Seizures [see Warnings and Precautions ( 5.6 )] Angle-Closure Glaucoma [see Warnings and Precautions ( 5.7 )] Hyponatremia [see Warnings and Precautions ( 5.8 )] QTc Prolongation [see Warnings and Precautions ( 5.10 )] Sexual Dysfunction [see Warnings and Precautions ( 5.12 )] Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled clinical trials with sertraline HCl were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Pharma, Inc. at 1-866-924-6266 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Sertraline HCl Capsules for the treatment of MDD and OCD is based on adequate and well-controlled studies of another sertraline HCl product. Below is a display of adverse reactions of sertraline HCl (referred to as “sertraline” in this section) from those adequate and well-controlled studies in MDD, OCD, and other conditions. The data described below reflect exposure in randomized, double-blind, placebo-controlled trials of sertraline in 3066 adults. These 3066 patients exposed to sertraline for 8 to 12 weeks represent 568 patient-years of exposure. The mean age was 40 years; 57% were females and 43% were males. The most common adverse reactions (≥5% and twice placebo) in all pooled placebo-controlled clinical trials of all sertraline-treated patients (MDD, OCD, and other conditions) were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 2). The following are the most common adverse reactions in trials of sertraline (≥5% and twice placebo) by indication that were not mentioned previously. MDD: somnolence OCD: insomnia, agitation Table 2: Common Adverse Reactions (Greater than 2% of Adults with MDD, OCD, and Other Conditions Treated with Sertraline Hydrochloride and Greater than or Equal to Twice the Incidence of Placebo) in Pooled Placebo-Controlled Trials* (1) Denominator used was for male patients only (n=1316 sertraline; n=973 placebo). * Adverse reactions that occurred greater than 2% in sertraline hydrochloride-treated patients and at least 2% greater in sertraline hydrochloride-treated patients than placebo-treated patients. Sertraline Hydrochloride (N=3066) % Placebo (N=2293) % Cardiac disorders Palpitations 4 2 Eye disorders Visual impairment 4 2 Gastrointestinal Disorders Nausea 26 12 Diarrhea/Loose Stools 20 10 Dry mouth 14 9 Dyspepsia 8 4 Constipation 6 4 Vomiting 4 1 General disorders and administration site conditions Fatigue 12 8 Metabolism and nutrition disorders Decreased appetite 7 2 Nervous system disorders Dizziness 12 8 Somnolence 11 6 Tremor 9 2 Psychiatric Disorders Insomnia 20 13 Agitation 8 5 Libido Decreased 6 2 Reproductive system and breast disorders Ejaculation failure (1) 8 1 Erectile dysfunction (1) 4 1 Ejaculation disorder (1) 3 0 Male sexual dysfunction (1) 2 0 Skin and subcutaneous tissue disorders Hyper…