SERTRALINE HYDROCHLORIDE- sertraline hydrochloride_tablet, film coated

Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT). Studies at clinically relevant doses have demonstrated that sertraline blocks the uptake of serotonin into human platelets. In vitro In vitro The effect of sertraline on the QTc interval was evaluated in a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QTc study in 54 healthy adult subjects. At 2-fold the maximum recommended daily dose (~3-fold the steady-state exposure for sertraline and N-desmethylsertraline), the largest mean ΔΔQTc was 10 ms with upper bound of two-sided 90% confidence interval of 12 ms. The length of the QTc interval was also positively correlated with serum concentrations of sertraline and N-desmethylsertraline concentrations. These concentration-based analyses, however, indicated a lesser effect on QTc at maximally observed concentration than in the primary analysis [See Warnings and Precautions (5) Adverse Reactions (6) Drug Interactions (7) Overdosage (10) Absorption max max max in vitro in vivo max min max [See Dosage and Administration (2. 1) Use in Specific Populations (8. 4) [See Use in Specific Populations (8. 5) [See Dosage and Administration (2. 4) Use in Specific Populations (8. 6) [See Use in Specific Populations (8. 7) max [See Drug Interactions (7. 1) [See Drug Interactions (7. 1) max [See Drug Interactions (7. 2) max [See Drug Interactions (7. 2) [See Drug Interactions (7. 2) in vivo max [See Drug Interactions (7.

Sertraline hydrochloride tablets are indicated for the treatment of the following [See Clinical Studies (14) Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD) Sertraline hydrochloride tablets are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of ( 1 Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD).

­Indication Starting Dosage Maximum Dosage MDD ( 2. 1 50 mg per day 200 mg per day OCD ( 2. 1 25 mg per day (ages 6 to 12) 200 mg per day PD, PTSD, SAD ( 2. 1 25 mg per day 200 mg per day PMDD ( 2. 2 50 mg per day 150 mg per day PMDD ( 2. 2 50 mg per day during luteal phase only 100 mg per day during luteal phase only If inadequate response to starting dosage, titrate in 25 to 50 mg per day increments once weekly in MDD, OCD, PD, PTSD, and SAD ( 2. 1 See Full Prescribing Information for titration in PMDD ( 2. 2 Hepatic impairment: Mild: Recommended starting and maximum dosage is half recommended dosage ( 2. 4 Moderate or severe: Not recommended ( 2. 4 When discontinuing sertraline hydrochloride tablets, reduce dose gradually ( 2. 4 The recommended initial dosage and maximum sertraline hydrochloride dosage in patients with MDD, OCD, PD, PTSD, and SAD are displayed in Table 1 below. A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage. For adults and pediatric patients, subsequent dosages may be increased in case of an inadequate response in 25 to 50 mg per day increments once a week, depending on tolerability, up to a maximum of 200 mg per day. Given the 24-hour elimination half-life of sertraline hydrochloride, the recommended interval between dose changes is one week. Table 1: Recommended Daily Dosage of Sertraline Hydrochloride in Patients with MDD, OCD, PD, PTSD, and SAD Indication Starting Dose Therapeutic Range Adults MDD 50 mg 50 to 200 mg OCD 50 mg PD, PTSD, SAD 25 mg Pediatric Patients OCD (ages 6 to 12 years old) 25 mg 50 to 200 mg OCD (ages 13 to 17 years old) 50 mg The recommended starting sertraline hydrochloride dosage in adult women with PMDD is 50 mg per day. Sertraline hydrochloride may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i. , starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses). Intermittent dosing would be repeated with each new cycle. When dosing continuously When dosing intermittently Prior to initiating treatment with sertraline hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [See Warnings and Precautions (5. 4) Both the recommended starting dosage and therapeutic range in patients with mild hepatic impairment (Child Pugh scores 5 or 6) are half the recommended daily dosage [See Dosage and Administration (2. 2) [See Use in Specific Populations (8. 6) Clinical Pharmacology (12. 3) At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of sertraline hydrochloride tablets. In addition, at least 14 days must elapse after stopping sertraline hydrochloride tablets before starting an MAOI antidepressant [See Contraindications (4) Warnings and Precautions (5. 2) Adverse reactions may occur upon discontinuation of sertraline hydrochloride tablets [See Warnings and Precautions (5.

The following adverse reactions are described in more detail in other sections of the prescribing information: Hypersensitivity reactions to sertraline [See Contraindications (4) QTc prolongation and ventricular arrhythmias when taken with pimozide [See Contraindications (4) Clinical Pharmacology (12. 2) Suicidal thoughts and behaviors [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/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) Sexual Dysfunction [See Warnings and Precautions (5. 11) Most common adverse reactions (>=5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido. 1 To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. MDD: somnolence; OCD: insomnia, agitation; PD: constipation, agitation; PTSD: fatigue; PMDD: somnolence, dry mouth, dizziness, fatigue, and abdominal pain; SAD: insomnia, dizziness, fatigue, dry mouth, malaise. Table 3: Common Adverse Reactions in Pooled Placebo-Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD* (1) * 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 Hyperhidrosis 7% 3% Adverse Reactions Leading to Discontinuation in Placebo-Controlled Clinical Trials MDD, OCD, PD, PTSD, SAD and PMDD: nausea (3%), diarrhea (2%), agitation (2%), and insomnia (2%). MDD (>2% and twice placebo): decreased appetite, dizziness, fatigue, headache, somnolence, tremor, and vomiting. OCD: somnolence. PD: nervousness and somnolence. Male and Female Sexual Dysfunction Table 4: Most Common Sexual Adverse Reactions (>=2% and twice placebo) in Men or Women from Sertraline Hydrochloride Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD Sertraline Hydrochloride Placebo Men only (N=1316) (N=973) Ejaculation failure 8% 1% Libido decreased 7% 2% Erectile dysfunction 4% 1% Ejaculation disorder 3% 0% Male sexual dysfunction 2% 0% Women only (N=1750) (N=1320) Libido decreased 4% 2% Adverse Reactions in Pediatric Patients Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with sertraline hydrochloride were: The following adverse reactions have been identified during postapproval use of sertraline hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac disorders [See Clinical Pharmacology (12. 2) Metabolism and nutrition disorders Musculoskeletal and connective tissue disorders Nervous system disorders disorders.

Sertraline hydrochloride tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5. 2) Drug Interactions (7. 1) Taking pimozide [See Drug Interactions (7. 1) With known hypersensitivity to sertraline (e. , anaphylaxis, angioedema) [See Adverse Reactions (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 5.

Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the neonate. 1 Pediatric use: Safety and effectiveness of sertraline hydrochloride in pediatric patients other than those with OCD have not been established. 4 Pregnancy Exposure Registry https://womensmentalhealth. org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5. 3) [See Data] [See Clinical Considerations]. Although no teratogenicity was observed in animal reproduction studies, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (MRHD) in rats and doses 3. 1 times the MRHD in rabbits on a mg/m 2 [See Data] The background risk of major birth defects and miscarriage for the indicated population are unknown. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise a pregnant woman of possible risks to the fetus when prescribing sertraline hydrochloride. Disease-associated maternal and/or embryo/fetal risk A prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. [see Warnings and Precautions (5. Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including sertraline hydrochloride in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). When treating a pregnant woman with sertraline hydrochloride during the third trimester, carefully consider both the potential risks and benefits of treatment. Monitor neonates who were exposed to sertraline hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [See Data]. Data Human Data Third Trimester Exposure Neonates exposed to sertraline hydrochloride and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on post-marketing reports. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [See Warnings and Precautions (5. 2) Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20 th First Trimester Exposure The weight of evidence from epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in pregnant women who were not exposed to sertraline. A meta-analysis of studies suggest no increase in the risk of total malformations (summary odds ratio=1. 01, 95% CI=0. 17) or cardiac malformations (summary odds ratio=0. 93, 95% CI=0. 23) among offspring of women with first trimester exposure to sertraline. An increased risk of congenital cardiac defects, specifically septal defects, the most common type of congenital heart defect, was observed in some published epidemiologic studies with first trimester sertraline exposure; however, most of these studies were limited by the use of comparison populations that did not allow for the control of confounders such as the underlying depression and associated conditions and behaviors, which may be factors associated with increased risk of these malformations. Reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and 40 mg/kg/day, respectively. These doses correspond to approximately 3. 1 times the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m 2 2 2 2 2 in utero Risk Summary [See Data] The safety and efficacy of sertraline hydrochloride have been established in the treatment of OCD in pediatric patients aged 6 to 17 [See Adverse Reactions (6. 1) Clinical Pharmacology (12. 3) Clinical Studies (14. 2) [See Boxed Warning Warnings and Precautions (5. 1) Of the total number of patients in clinical studies of sertraline hydrochloride in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 797 (17%) were >= 65 years old, while 197 (4%) were >= 75 years old. [See Adverse Reactions (6. 1) [See Warnings and Precautions (5. The recommended dosage in patients with mild hepatic impairment (Child-Pugh score 5 or 6) is half the recommended dosage due to increased exposure in this patient population. The use of sertraline hydrochloride in patients with moderate (Child-Pugh score 7 to 10) or severe hepatic impairment (Child-Pugh score 10 to 15) is not recommended, because sertraline hydrochloride is extensively metabolized, and the effects of sertraline hydrochloride in patients with moderate and severe hepatic impairment have not been studied [See Dosage and Administration (2. 4) Clinical Pharmacology (12. 3) No dose adjustment is needed in patients with mild to severe renal impairment. Sertraline exposure does not appear to be affected by renal impairment [See Clinical Pharmacology (12.

Protein-bound drugs: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs (e. , warfarin) as warranted. 3 CYP2D6 substrates: Reduce dosage of drugs metabolized by CYP2D6. 3 Table 5 includes clinically significant drug interactions with sertraline hydrochloride [See Clinical Pharmacology (12. Clinically-Significant Drug Interactions with Sertraline Hydrochloride Clinical Impact: The concomitant use of SSRIs including sertraline hydrochloride and MAOIs increases the risk of serotonin syndrome. Intervention: Sertraline hydrochloride is 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 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 hydrochloride is contraindicated [See Contraindications (4) Clinical Impact: The concomitant use of serotonergic drugs with sertraline hydrochloride 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 hydrochloride and/or concomitant serotonergic drugs [See Warnings and Precautions (5. 2) Examples: Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with sertraline hydrochloride may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [See Warnings and Precautions (5. 3) Examples: aspirin, clopidogrel, heparin, warfarin Clinical Impact: Sertraline hydrochloride is highly bound to plasma protein. The concomitant use of sertraline hydrochloride with another drug that is highly bound to plasma protein may increase free concentrations of sertraline hydrochloride or other tightly-bound drugs in plasma [See Clinical Pharmacology (12. 3) Intervention: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs as warranted. Examples: warfarin Clinical Impact: Sertraline hydrochloride is a CYP2D6 inhibitor [See Clinical Pharmacology (12. 3) Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant sertraline hydrochloride use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if sertraline hydrochloride is discontinued. Examples: propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thioridazine, tolterodine, venlafaxine Clinical Impact: Phenytoin is a narrow therapeutic index drug. Sertraline hydrochloride may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating sertraline hydrochloride. Reduce phenytoin dosage if needed. Examples: phenytoin, fosphenytoin Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e. , TdP) is increased with concomitant use of 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. Avoid the concomitant use of drugs known to prolong the QTc interval. Examples: Specific antipsychotics (e. , ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e. , erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e. , quinidine, procainamide); Class III antiarrhythmics (e. , amiodarone, sotalol); and others (e. , pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). Based on pharmacokinetic studies, no dosage adjustment of sertraline hydrochloride is necessary when used in combination with cimetidine. Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when sertraline hydrochloride is administered concomitantly [See Clinical Pharmacology (12. 3) False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines.

OVERDOSAGE
The following have been reported with sertraline tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a sertraline overdose. Consider contacting a Poison Center (1-800-221-2222) or a medical toxicologist for additional overdosage management recommendations.
NONCLINICAL TOXICOLOGY
Carcinogenesis 2 2 2 2 in vivo in vitro 2
CLINICAL STUDIES
Efficacy of sertraline hydrochloride was established in the following trials: MDD: two short-term trials and one maintenance trials in adults [See Clinical Studies (14. 1) OCD: three short-term trials in adults and one short-term trial in pediatric patients [See Clinical Studies (14. 2) PD: three short-term trials and one maintenance trial in adults [See Clinical Studies (14. 3) PTSD: two short-term trials and one maintenance trial in adults [See Clinical Studies (14. 4) SAD: two short-term trials and one maintenance trial in adults [See Clinical Studies (14. 5) PMDD: two short-term trials in adult female patients [See Clinical Studies (14. 6) The efficacy of sertraline hydrochloride as a treatment for MDD was established in two randomized, double-blind, placebo-controlled studies and one double-blind, randomized-withdrawal study following an open label study in adult (ages 18 to 65) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria for MDD (studies MDD-1 and MDD-2). Study MDD-1 was an 8-week, 3-arm study with flexible dosing of sertraline hydrochloride, amitriptyline, and placebo. Adult patients received sertraline hydrochloride (N=126, in a daily dose titrated weekly to 50 mg, 100 mg, or 200 mg), amitriptyline (N=123, in a daily dose titrated weekly to 50 mg, 100 mg, or 150 mg), or placebo (N= 130). Study MDD-2 was a 6-week, multicenter parallel study of three fixed doses of sertraline hydrochloride administered once daily at 50 mg (N=82), 100 mg (N=75), and 200 mg (N=56) doses and placebo (N=76) in the treatment of adult outpatients with MDD. Overall, these studies demonstrated sertraline hydrochloride to be superior to placebo on the Hamilton Rating Scale for Depression (HAMD-17) and the Clinical Global Impression Severity (CGI-S) of Illness and Global Improvement (CGI-I) scores. Study MDD-2 was not readily interpretable regarding a dose response relationship for effectiveness. Adults with OCD Study OCD-1 was an 8-week randomized, placebo-controlled study with flexible dosing of sertraline hydrochloride in a range of 50 to 200 mg/day, titrated in 50 mg increments every 4 days to a maximally tolerated dose; the mean dose for completers was 186 mg/day. Patients receiving sertraline hydrochloride (N=43) experienced a mean reduction of approximately 4 points on the Y-BOCS total score which was statistically significantly greater than the mean reduction of 2 points in placebo-treated patients (N=44). The mean change in Y-BOCS from baseline to last visit (the primary efficacy endpoint) was -3. 79 (sertraline hydrochloride) and -1. 48 (placebo). Study OCD-2 was a 12-week randomized, placebo-controlled fixed-dose study, including sertraline hydrochloride doses of 50, 100, and 200 mg/day. Sertraline hydrochloride (N=240) was titrated to the assigned dose over two weeks in 50 mg increments every 4 days. Patients receiving sertraline hydrochloride doses of 50 and 200 mg/day experienced mean reductions of approximately 6 points on the Y-BOCS total score, which were statistically significantly greater than the approximately 3 point reduction in placebo-treated patients (N=84). The mean change in Y-BOCS from baseline to last visit (the primary efficacy endpoint) was -5. 7 (pooled results from sertraline hydrochloride 50 mg, 100 mg, and 150 mg) and -2. 85 (placebo). Study OCD-3 was a 12-week randomized, placebo controlled study with flexible dosing of sertraline hydrochloride in a range of 50 to 200 mg/day; the mean dose for completers was 185 mg/day. Sertraline hydrochloride (N=241) was titrated to the assigned dose over two weeks in 50 mg increments every 4 days. Patients receiving sertraline hydrochloride experienced a mean reduction of approximately 7 points on the Y-BOCS total score which was statistically significantly greater than the mean reduction of approximately 4 points in placebo-treated patients (N=84). The mean change in Y-BOCS from baseline to last visit (the primary efficacy endpoint) was - 6. 5 (sertraline hydrochloride) and -3. 6 (placebo). Analyses for age and gender effects on outcome did not suggest any differential responsiveness on the basis of age or sex. Condition 1: Y-BOCS score increased by >= 5 points, to a minimum of 20, relative to baseline; Condition 2: CGI-I increased by >= one point; and Condition 3: Worsening of the patient’s condition in the investigator’s judgment, to justify alternative treatment. Patients receiving continued sertraline hydrochloride treatment experienced a statistically significantly lower rate of discontinuation due to relapse or insufficient clinical response over the subsequent 28 weeks compared to those receiving placebo. This pattern was demonstrated in male and female subjects. The effectiveness of sertraline hydrochloride in the treatment of PD was demonstrated in three double-blind, placebo-controlled studies (Studies PD-1, PD-2, and PD-3) of adult outpatients who had a primary diagnosis of PD (DSM-III-R), with or without agoraphobia. Studies PD-1 and PD-2 were 10-week flexible dose studies of sertraline hydrochloride (N=80 study PD-1 and N=88 study PD-2) compared to placebo (N=176 study PD-1 and PD-2). In both studies, sertraline hydrochloride was initiated at 25 mg/day for the first week, then titrated in weekly increments of 50 mg per day to a maximum dose of 200 mg/day on the basis of clinical response and toleration. The mean sertraline hydrochloride doses for completers to 10 weeks were 131 mg/day and 144 mg/day, respectively, for Studies PD-1 and PD-2. In these studies, sertraline hydrochloride was shown to be statistically significantly more effective than placebo on change from baseline in panic attack frequency and on the Clinical Global Impression Severity (CGI-S) of Illness and Global Improvement (CGI-­I) scores. The difference between sertraline hydrochloride and placebo in reduction from baseline in the number of full panic attacks was approximately 2 panic attacks per week in both studies. Study PD-3 was a 12-week randomized, double-blind fixed-dose study, including sertraline hydrochloride doses of 50, 100, and 200 mg/day. Patients receiving sertraline hydrochloride (50 mg N=43, 100 mg N=44, 200 mg N=45) experienced a statistically significantly greater reduction in panic attack frequency than patients receiving placebo (N=45). Study PD-3 was not readily interpretable regarding a dose response relationship for effectiveness. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age, race, or gender. In Study PD-4, patients meeting DSM-III-R criteria for PD who had responded during a 52-week open trial on sertraline hydrochloride 50 to 200 mg/day (n=183) were randomized to continuation of sertraline hydrochloride or to substitution of placebo for up to 28 weeks of observation for discontinuation due to relapse or insufficient clinical response. Response during the open phase was defined as a CGI-I score of 1(very much improved) or 2 (much improved). Insufficient clinical response in the double-blind phase indicated a worsening of the patient’s condition that resulted in study discontinuation, as assessed by the investigator. Relapse during the double-blind phase was defined as the following conditions being met on three consecutive visits: (1) CGI-I >= 3; Patients receiving continued sertraline hydrochloride treatment experienced a statistically significantly lower rate of discontinuation due to relapse or insufficient clinical response over the subsequent 28 weeks compared to those receiving placebo. The effectiveness of sertraline hydrochloride in the treatment of PTSD was established in two multicenter placebo-controlled studies (Studies PSTD-1 and PSTD-2) of adult outpatients who met DSM-III-R criteria for PTSD. The mean duration of PTSD for these patients was 12 years (Studies PSTD-1 and PSTD-2 combined) and 44% of patients (169 of the 385 patients treated) had secondary depressive disorder. (1) CGI-I >= 3; Patients receiving continued sertraline hydrochloride treatment experienced statistically significantly lower relapse rates over the subsequent 28 weeks compared to those receiving placebo. The effectiveness of sertraline hydrochloride in the treatment of SAD (also known as social phobia) was established in two multicenter, randomized, placebo-controlled studies (Study SAD-1 and SAD-2) of adult outpatients who met DSM-­IV criteria for SAD. (1) Liebowitz Social Anxiety Scale (LSAS), a 24-item clinician administered instrument that measures fear, anxiety, and avoidance of social and performance situations, and Sertraline hydrochloride was statistically significantly more effective than placebo as measured by the LSAS and the percentage of responders. (1) Duke Brief Social Phobia Scale (BSPS), a multi-item clinician-rated instrument that measures fear, avoidance and physiologic response to social or performance situations, Sertraline hydrochloride was shown to be statistically significantly more effective than placebo as measured by the BSPS total score and fear, avoidance and physiologic factor scores, as well as the FQ-SPS total score, and to have statistically significantly more responders than placebo as defined by the CGI-I. Subgroup analyses did not suggest differences in treatment outcome on the basis of gender. There was insufficient information to determine the effect of race or age on outcome. The effectiveness of sertraline hydrochloride for the treatment of PMDD was established in two double-blind, parallel group, placebo-controlled flexible dose trials (Studies PMDD-1 and PMDD-2) conducted over 3 menstrual cycles in adult female patients. The effectiveness of sertraline hydrochloride for PMDD for more than 3 menstrual cycles has not been systematically evaluated in controlled trials. In Study PMDD-1, involving 251 randomized patients, (n=125 on sertraline hydrochloride and n=126 on placebo), sertraline hydrochloride treatment was initiated at 50 mg/day and administered daily throughout the menstrual cycle. In subsequent cycles, sertraline hydrochloride was titrated in 50 mg increments at the beginning of each menstrual cycle up to a maximum of 150 mg/day on the basis of clinical response and tolerability. The mean dose for completers was 102 mg/day. Sertraline hydrochloride administered daily throughout the menstrual cycle was statistically significantly more effective than placebo on change from baseline to endpoint on the DRSP total score, the HAMD-17 total score, and the CGI-S score, as well as the CGI-I score at endpoint. In Study PMDD-2, involving 281 randomized patients, (n=142 on sertraline hydrochloride and n=139 on placebo), sertraline hydrochloride treatment was initiated at 50 mg/day in the late luteal phase (last 2 weeks) of each menstrual cycle and then discontinued at the onset of menses (intermittent dosing). In subsequent cycles, patients were dosed in the range of 50 to 100 mg/day in the luteal phase of each cycle, on the basis of clinical response and tolerability. Patients who received 100 mg/day started with 50 mg/day for the first 3 days of the cycle, then 100 mg/day for the remainder of the cycle. The mean sertraline hydrochloride dose for completers was 74 mg/day. Sertraline hydrochloride administered in the late luteal phase of the menstrual cycle was statistically significantly more effective than placebo on change from baseline to endpoint on the DRSP total score and the CGI-S score, as well as the CGI-I score at endpoint (Week 12). There was insufficient information to determine the effect of race or age on outcome in these studies.
Medication Guide
Sertraline Hydrochloride Tablets USP (ser'' tra leen hye'''' droe klor'' ide) What is the most important information I should know about sertraline hydrochloride tablets? Sertraline hydrochloride tablets and other antidepressant medicines may cause serious side effects. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if there is an emergency. 1. Suicidal thoughts or actions: Sertraline hydrochloride tablets and other antidepressant medicines may increase suicidal thoughts or actions first few months of treatment or when the dose is changed Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice new or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when sertraline hydrochloride tablets is started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting aggressive or violent new or worse depression feeling agitated, restless, angry or irritable an increase in activity or talking more than what is normal for you acting on dangerous impulses thoughts about suicide or dying new or worse anxiety or panic attacks trouble sleeping other unusual changes in behavior or mood 2. Serotonin Syndrome. agitation, hallucinations, coma, or other changes in mental status racing heartbeat, high or low blood pressure coordination problems or muscle twitching (overactive reflexes) nausea, vomiting, or diarrhea sweating or fever muscle rigidity 3. Increased chance of bleeding registered registered 4. Manic episodes. greatly increased energy racing thoughts unusually grand ideas severe trouble sleeping reckless behavior excessive happiness or irritability talking more or faster than usual 5. Seizures or convulsions. 6. Glaucoma (angle-closure glaucoma). 7. Changes in appetite or weight. 8. Low salt (sodium) levels in the blood headache weakness or feeling unsteady confusion, problems concentrating or thinking, or memory problems 9. Sexual problems (dysfunction). Symptoms in males may include: Delayed ejaculation or inability to have an ejaculation Decreased sex drive Problems getting or keeping an erection Symptoms in females may include: Decreased sex drive Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with sertraline hydrochloride tablets. There may be treatments your healthcare provider can suggest. Do not stop sertraline hydrochloride tablets without first talking to your healthcare provider. anxiety, irritability, high or low mood, feeling restless or changes in sleep habits headache, sweating, nausea, dizziness electric shock-like sensations, shaking, confusion What are sertraline hydrochloride tablets? Major Depressive Disorder (MDD) Panic Disorder Social Anxiety Disorder Obsessive Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Premenstrual Dysphoric Disorder (PMDD) It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Who should not take sertraline hydrochloride tablets? Do not take sertraline hydrochloride tablets if you: take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. have taken an MAOI within 2 weeks of stopping sertraline hydrochloride tablets unless directed to do so by your healthcare provider. have stopped taking an MAOI in the last 2 weeks unless directed to do so by your healthcare provider. take any other medicines that contain sertraline (such as sertraline HCl or sertraline hydrochloride). take the antipsychotic medicine pimozide (Orapregistered) because this can cause serious heart problems. are allergic to sertraline or any of the ingredients in sertraline hydrochloride tablets. See the end of this Medication Guide for a complete list of ingredients in sertraline hydrochloride tablets. take Antabuseregistered (disulfiram) (if you are taking the liquid form of sertraline hydrochloride tablets) due to the alcohol content. People who take sertraline hydrochloride tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever rapid changes in heart rate or blood pressure uncontrolled muscle spasms confusion stiff muscles loss of consciousness (pass out) What should I tell my healthcare provider before taking sertraline hydrochloride tablets? Before starting sertraline hydrochloride tablets, tell your healthcare provider: if you have: liver problems heart problems bipolar disorder or mania kidney problems or have had seizures or convulsions low sodium levels in your blood a history of a stroke high blood pressure or have had bleeding problems are pregnant or plan to become pregnant. There is a pregnancy registry for females who are exposed to sertraline hydrochloride tablets during pregnancy. The purpose of the registry is to collect information about the health of females exposed to sertraline hydrochloride tablets and their baby. If you or your child become pregnant during treatment with sertraline hydrochloride tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-866-961-2388 or by visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. are breastfeeding or plan to breastfeed Tell your healthcare provider about all the medicines that you take, Especially tell your healthcare provider if you or your child take: medicines used to treat migraine headaches called triptans tricyclic antidepressants lithium tramadol, fentanyl, meperidine, methadone, or other opioids tryptophan buspirone amphetamines phenytoin St. John’s Wort medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet medicines, warfarin, and other anticoagulants diuretics medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) Sertraline hydrochloride tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects. Do not How should I take sertraline hydrochloride tablets? Take sertraline hydrochloride tablets exactly as prescribed. Your healthcare provider may need to change the dose of sertraline hydrochloride tablets until it is the right dose for you. Sertraline hydrochloride tablets may be taken with or without food. If you miss a dose of sertraline hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not If you take too much sertraline hydrochloride, call your healthcare provider or poison control center right away, or go to the nearest hospital emergency room right away. What should I avoid while taking sertraline hydrochloride tablets? Sertraline hydrochloride tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how sertraline hydrochloride tablets affect you. Do not What are the possible side effects of sertraline hydrochloride tablets? Sertraline hydrochloride tablets may cause serious side effects, including: See “What is the most important information I should know about sertraline hydrochloride tablets?” The most common side effects in adults who take sertraline hydrochloride tablets include: nausea, loss of appetite, diarrhea, or indigestion increased sweating tremor or shaking agitation change in sleep habits including increased sleepiness or insomnia sexual problems including decreased libido and ejaculation failure feeling tired or fatigued anxiety The most common side effects in children and adolescents who take include How should I store sertraline hydrochloride tablets? Store sertraline hydrochloride tablets at room temperature, 20° to 25°C (68° to 77°F). Keep sertraline hydrochloride tablets bottle closed tightly. Keep sertraline hydrochloride tablets and all medicines out of the reach of children. What are the ingredients in sertraline hydrochloride tablets? Active ingredient: Inactive ingredients: Tablets: Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

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SERTRALINE HYDROCHLORIDE- sertraline hydrochloride_tablet, film coated Product manual source documgent