Sertraline
Generic: SERTRALINE
Basic Information
Manufacturer
A-S Medication Solutions
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
ad69cbfe-5b42-4714-a999-77d474e0849d
Indications & Usage
1 INDICATIONS AND USAGE 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)
Adverse Reactions
6 ADVERSE REACTIONS 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.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc.
at 1-866-901-DRUG (3784) 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 data described below are from randomized, double-blind, placebo-controlled trials of sertraline hydrochloride (mostly 50 mg to 200 mg per day) in 3,066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD.
These 3,066 patients exposed to sertraline hydrochloride for 8 to12 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 hydrochloride -treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3).
The following are the most common adverse reactions in trials of sertraline hydrochloride (>5% and twice placebo) by indication that were not mentioned previously.
• 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) Denominator used was for male patients only (n=1,316 sertraline hydrochloride; 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 = 3,066 ) Placebo ( N = 2,293 ) Cardiac disorders Palpitations 4% 2% Eye disorders Visual impairment 4% 2% Gastrointestinal d isorders 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 In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3,066 patients who received sertraline hydrochloride discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2,293 placebo-treated patients.
In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in sertraline hydrochloride -treated patients: • 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 Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment.
However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them.
Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence.
Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of sertraline hydrochloride -treated patients and twice placebo from pooled placebo-controlled trials.
For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction.
For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido.
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 = 1,316 ) ( 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 = 1,750 ) ( N = 1,320 ) Libido decreased 4% 2% Adverse Reactions in Pediatric Patients In 281 pediatric patients treated with sertraline hydrochloride in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies.
Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety.
Other Adverse Reactions Observed During the Premarketing Evaluation of Sertraline Hydrochloride Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of <2% in patients treated with sertraline hydrochloride were: Cardiac disorders - tachycardia Ear and labyrinth disorder s - tinnitus Endocrine disorders - hypothyroidism Eye disorders - mydriasis, blurred vision Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - e dema, gait disturbance, irritability, pyrexia Hepatobiliary disorders - elevated liver enzymes Immune system disorders - anaphylaxis Metabolism and nutrition disorders - diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite Musculoskeletal and connective tissue disorders - arthralgia, muscle spasms, tightness, or twitching Nervous system disorders - ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope Psychiatric disorders - aggression, bruxism, confusional state, euphoric mood, hallucination Renal and urinary disorders - hematuria Reproductive system and breast disorders - galactorrhea, priapism, vaginal hemorrhage Respiratory, thoracic and mediastinal disorders - bronchospasm, epistaxis, yawning Skin and subcutaneous tissue disorders - alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria Vascular disorders - hemorrhage, hypertension, vasodilation 6.2 Post-marketing Experience The following adverse reactions have been identified during postapproval use of sertraline hydrochloride tablet.
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.
Bleeding or clotting disorders - increased coagulation times (altered platelet function) Cardiac disorder s - AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including Torsade de Pointes) [See Clinical Pharmacology ( 12.2 )] Endocrine disorders - gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH Eye disorders - blindness, optic neuritis, cataract Hepatobiliary disorders - severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis Hemic and lymphatic d isorders - agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness Immune system disorders - angioedema Metabolism and nutrition disorders - hyponatremia, hyperglycemia Musculoskeletal and connective tissue disorders - rhabdomyolysis, trismus Nervous system disorders - serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis Psychiatric disorders - psychosis, enuresis, paroniria Renal and urinary disorders - acute renal failure Respiratory, thoracic and mediastinal disorders - pulmonary hypertension, eosinophilic pneumonia, anosmia, hyposmia Skin and subcutaneous tissue disorders - photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Vascular disorders - cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call- Fleming syndrome), vasculitis
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc.
at 1-866-901-DRUG (3784) 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 data described below are from randomized, double-blind, placebo-controlled trials of sertraline hydrochloride (mostly 50 mg to 200 mg per day) in 3,066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD.
These 3,066 patients exposed to sertraline hydrochloride for 8 to12 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 hydrochloride -treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3).
The following are the most common adverse reactions in trials of sertraline hydrochloride (>5% and twice placebo) by indication that were not mentioned previously.
• 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) Denominator used was for male patients only (n=1,316 sertraline hydrochloride; 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 = 3,066 ) Placebo ( N = 2,293 ) Cardiac disorders Palpitations 4% 2% Eye disorders Visual impairment 4% 2% Gastrointestinal d isorders 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 In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3,066 patients who received sertraline hydrochloride discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2,293 placebo-treated patients.
In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in sertraline hydrochloride -treated patients: • 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 Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment.
However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them.
Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence.
Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of sertraline hydrochloride -treated patients and twice placebo from pooled placebo-controlled trials.
For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction.
For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido.
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 = 1,316 ) ( 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 = 1,750 ) ( N = 1,320 ) Libido decreased 4% 2% Adverse Reactions in Pediatric Patients In 281 pediatric patients treated with sertraline hydrochloride in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies.
Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety.
Other Adverse Reactions Observed During the Premarketing Evaluation of Sertraline Hydrochloride Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of <2% in patients treated with sertraline hydrochloride were: Cardiac disorders - tachycardia Ear and labyrinth disorder s - tinnitus Endocrine disorders - hypothyroidism Eye disorders - mydriasis, blurred vision Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - e dema, gait disturbance, irritability, pyrexia Hepatobiliary disorders - elevated liver enzymes Immune system disorders - anaphylaxis Metabolism and nutrition disorders - diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite Musculoskeletal and connective tissue disorders - arthralgia, muscle spasms, tightness, or twitching Nervous system disorders - ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope Psychiatric disorders - aggression, bruxism, confusional state, euphoric mood, hallucination Renal and urinary disorders - hematuria Reproductive system and breast disorders - galactorrhea, priapism, vaginal hemorrhage Respiratory, thoracic and mediastinal disorders - bronchospasm, epistaxis, yawning Skin and subcutaneous tissue disorders - alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria Vascular disorders - hemorrhage, hypertension, vasodilation 6.2 Post-marketing Experience The following adverse reactions have been identified during postapproval use of sertraline hydrochloride tablet.
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.
Bleeding or clotting disorders - increased coagulation times (altered platelet function) Cardiac disorder s - AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including Torsade de Pointes) [See Clinical Pharmacology ( 12.2 )] Endocrine disorders - gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH Eye disorders - blindness, optic neuritis, cataract Hepatobiliary disorders - severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis Hemic and lymphatic d isorders - agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness Immune system disorders - angioedema Metabolism and nutrition disorders - hyponatremia, hyperglycemia Musculoskeletal and connective tissue disorders - rhabdomyolysis, trismus Nervous system disorders - serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis Psychiatric disorders - psychosis, enuresis, paroniria Renal and urinary disorders - acute renal failure Respiratory, thoracic and mediastinal disorders - pulmonary hypertension, eosinophilic pneumonia, anosmia, hyposmia Skin and subcutaneous tissue disorders - photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Vascular disorders - cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call- Fleming syndrome), vasculitis