Data from FDA - Curated by EPG Health - Last updated 30 April 2018

Indication(s)

1 INDICATIONS AND USAGE ZOLOFT is 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) ZOLOFT is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of (1): Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Post-traumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD)

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Advisory information

contraindications
4 CONTRAINDICATIONS ZOLOFT is 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.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1, 6.2)]. In addition to the contraindications for all ZOLOFT formulations listed above, ZOLOFT oral solution is contraindicated in patients: Taking disulfiram. ZOLOFT oral solution contains alcohol, and concomitant use of ZOLOFT and disulfiram may result in a disulfiram-alcohol reaction. 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, 5.4) ZOLOFT oral solution only: Concomitant use of disulfiram (4)
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)] Disulfiram-alcohol reaction when ZOLOFT oral solution is taken with disulfiram [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)] 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 Pfizer Inc at 1-800-438-1985 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 ZOLOFT (mostly 50 mg to 200 mg per day) in 3066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD. These 3066 patients exposed to ZOLOFT 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 ZOLOFT-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 ZOLOFT (≥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 PMDDAdverse reactions that occurred greater than 2% in ZOLOFT-treated patients and at least 2% greater in ZOLOFT-treated patients than placebo-treated patients. ZOLOFT (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 Denominator used was for male patients only (n=1316 ZOLOFT; n=973 placebo). 8% 1% Erectile dysfunction 4% 1% Ejaculation disorder 3% 0% Male sexual dysfunction 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 3066 patients who received ZOLOFT discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2293 placebo-treated patients. In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in ZOLOFT-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 ZOLOFT-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 ZOLOFT Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD ZOLOFT 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 In 281 pediatric patients treated with ZOLOFT 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 ZOLOFT Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with ZOLOFT were: Cardiac disorders – tachycardia Ear and labyrinth disorders – tinnitus Endocrine disorders - hypothyroidism Eye disorders - mydriasis, blurred vision Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - edema, 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 ZOLOFT. 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 disorders - 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 disorders - 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 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

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Indication Starting Dosage Maximum Dosage MDD (2.1) 50 mg per day 200 mg per day OCD (2.1) 25 mg per day (ages 6–12) 50 mg per day (ages ≥ 13) 200 mg per day PD, PTSD, SAD (2.1) 25 mg per day 200 mg per day PMDD (2.2) continuous dosing 50 mg per day 150 mg per day PMDD (2.2) intermittent dosing 50 mg per day during luteal phase only 100 mg per day during luteal phase only If inadequate response to starting dosage, titrate in 25–50 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 ZOLOFT, reduce dose gradually (2.6, 5.4) Oral solution: Must be diluted before administration (2.7) 2.1 Dosage in Patients with MDD, OCD, PD, PTSD, and SAD The recommended initial dosage and maximum ZOLOFT 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 ZOLOFT, the recommended interval between dose changes is one week. Table 1: Recommended Daily Dosage of ZOLOFT in Patients with MDD, OCD, PD, PTSD, and SAD Indication Starting Dose Therapeutic Range Adults MDD 50 mg 50–200 mg OCD 50 mg PD, PTSD, SAD 25 mg Pediatric Patients OCD (ages 6–12 years old) 25 mg 50–200 mg OCD (ages 13–17 years old) 50 mg 2.2 Dosage in Patients with PMDD The recommended starting ZOLOFT dosage in adult women with PMDD is 50 mg per day. ZOLOFT may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., 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, patients not responding to a 50 mg dosage may benefit from dosage increases at 50 mg increments per menstrual cycle up to 150 mg per day. When dosing intermittently, patients not responding to a 50 mg dosage may benefit from increasing the dosage up to a maximum of 100 mg per day during the next menstrual cycle (and subsequent cycles) as follows: 50 mg per day during the first 3 days of dosing followed by 100 mg per day during the remaining days in the dosing cycle. 2.3 Screen for Bipolar Disorder Prior to Starting ZOLOFT Prior to initiating treatment with ZOLOFT 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 Dosage Modifications in Patients with Hepatic Impairment 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 (2.1, 2.2)]. The use of ZOLOFT in patients with moderate (Child Pugh scores 7 to 9) or severe hepatic impairment (Child Pugh scores 10–15) is not recommended [See Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. 2.5 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 ZOLOFT. In addition, at least 14 days must elapse after stopping ZOLOFT before starting an MAOI antidepressant [See Contraindications (4), Warnings and Precautions (5.2)]. 2.6 Discontinuation of Treatment with ZOLOFT Adverse reactions may occur upon discontinuation of ZOLOFT [See Warnings and Precautions (5.5)]. Gradually reduce the dosage rather than stopping ZOLOFT abruptly whenever possible. 2.7 Preparation of ZOLOFT Oral Solution ZOLOFT oral solution must be diluted before use. Use the supplied calibrated dropper to measure the amount of ZOLOFT oral solution needed Note: The supplied calibrated dropper has 25 mg and 50 mg graduation marks only Mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. After mixing, a slight haze may appear, which is normal. Instruct patients or caregivers to immediately take the dose after mixing.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the neonate (8.1) Pediatric use: Safety and effectiveness of ZOLOFT in pediatric patients other than those with OCD have not been established (8.4) 8.1 Pregnancy Risk Summary Overall, available published 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 comparator populations. Some studies have reported increases for specific major birth defects; however, these study results are inconclusive [See Data]. There are clinical considerations regarding neonates exposed to SSRIs and SNRIs, including ZOLOFT, during the third trimester of pregnancy [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/m2 basis in adolescents. When sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first four days after birth at the MRHD [See Data]. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Advise a pregnant woman of possible risks to the fetus when prescribing ZOLOFT. ZOLOFT oral solution contains 12% alcohol and is not recommended during pregnancy because there is no known safe level of alcohol exposure during pregnancy. Clinical Considerations 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. Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including ZOLOFT 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 ZOLOFT during the third trimester, carefully consider both the potential risks and benefits of treatment. Monitor neonates who were exposed to ZOLOFT in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [See Data]. Data Human Data Third Trimester Exposure Neonates exposed to ZOLOFT 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 1–2 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 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997–2005 found a PPHN risk ratio of 2.4 (95% CI 1.2–4.3) associated with patient-reported maternal use of SSRIs "in early pregnancy" and a PPHN risk ratio of 3.6 (95% CI 1.2–8.3) associated with a combination of patient-reported maternal use of SSRIs "in early pregnancy" and an antenatal SSRI prescription "in later pregnancy". 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=0.88–1.17) or cardiac malformations (summary odds ratio=0.93, 95% CI=0.70–1.23) 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. Animal Data 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/m2 basis in adolescents. There was no evidence of teratogenicity at any dose level. When pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0.4 times the MRHD on a mg/m2 basis) in rats and 40 mg/kg (3.1 times the MRHD on a mg/m2 basis) in rabbits. When female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth. Pup body weights were also decreased during the first four days after birth. These effects occurred at a dose of 20 mg/kg (0.8 times the MRHD on a mg/m2 basis). The no effect dose for rat pup mortality was 10 mg/kg (0.4 times the MRHD on a mg/m2 basis). The decrease in pup survival was shown to be due to in utero exposure to sertraline. The clinical significance of these effects is unknown. 8.2 Lactation Risk Summary Available data from published literature demonstrate low levels of sertraline and its metabolites in human milk [See Data]. There are no data on the effects of sertraline on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZOLOFT and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. Data In a published pooled analysis of 53 mother-infant pairs, exclusively human milk-fed infants had an average of 2% (range 0% to 15%) of the sertraline serum levels measured in their mothers. No adverse reactions were observed in these infants. 8.4 Pediatric Use The safety and efficacy of ZOLOFT 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)]. Safety and effectiveness in pediatric patients in patients with OCD below the age of 6 have not been established. Safety and effectiveness have not been established in pediatric patients for indications other than OCD. Two placebo-controlled trials were conducted in pediatric patients with MDD, but the data were not sufficient to support an indication for use in pediatric patients. Monitoring Pediatric Patients Treated with ZOLOFT Monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dose increases or decreases [See Boxed Warning, Warnings and Precautions (5.1)]. Decreased appetite and weight loss have been observed with the use of SSRIs. Monitor weight and growth in pediatric patients treated with an SSRI such as ZOLOFT. Weight Loss in Studies in Pediatric Patients with MDD In a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50–200 mg) outpatient trials for MDD (n=373), there was a difference in weight change between ZOLOFT and placebo of roughly 1 kg, for both children (ages 6–11) and adolescents (ages 12–17), in both age groups representing a slight weight loss for the ZOLOFT group compared to a slight gain for the placebo group. For children, about 7% of the ZOLOFT-treated patients had a weight loss greater than 7% of body weight compared to 0% of the placebo-treated patients; for adolescents, about 2% of ZOLOFT-treated patients had a weight loss > 7% of body weight compared to about 1% of placebo-treated patients. A subset of patients who completed the randomized controlled trials in patients with MDD (ZOLOFT n=99, placebo n=122) were continued into a 24-week, flexible-dose, open-label, extension study. Those subjects who completed 34 weeks of ZOLOFT treatment (10 weeks in a placebo-controlled trial + 24 weeks open-label, n=68) had weight gain that was similar to that expected using data from age-adjusted peers. However, there are no studies that directly evaluate the long-term effects of ZOLOFT on the growth, development, and maturation in pediatric patients. Alcohol Content in ZOLOFT Oral Solution ZOLOFT oral solution contains 12% alcohol. Juvenile Animal Data A study conducted in juvenile rats at clinically relevant doses showed delay in sexual maturation, but there was no effect on fertility in either males or females. In this study in which juvenile rats were treated with oral doses of sertraline at 0, 10, 40 or 80 mg/kg/day from postnatal day 21 to 56, a delay in sexual maturation was observed in males treated with 80 mg/kg/day and females treated with doses ≥10 mg/kg/day. There was no effect on male and female reproductive endpoints or neurobehavioral development up to the highest dose tested (80 mg/kg/day), except a decrease in auditory startle response in females at 40 and 80 mg/kg/day at the end of treatment but not at the end of the drug –free period. The highest dose of 80 mg/kg/day produced plasma levels (AUC) of sertraline 5 times those seen in pediatric patients (6 – 17 years of age) receiving the maximum recommended dose of sertraline (200 mg/day). 8.5 Geriatric Use Of the total number of patients in clinical studies of ZOLOFT in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In 354 geriatric subjects treated with ZOLOFT in MDD placebo-controlled trials, the overall profile of adverse reactions was generally similar to that shown in Table 3[See Adverse Reactions (6.1)], except for tinnitus, arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients. SNRIs and SSRIs, including ZOLOFT, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [See Warnings and Precautions (5.8)]. 8.6 Hepatic Impairment 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 ZOLOFT in patients with moderate (Child-Pugh score 7 to 10) or severe hepatic impairment (Child-Pugh score 10–15) is not recommended, because ZOLOFT is extensively metabolized, and the effects of ZOLOFT in patients with moderate and severe hepatic impairment have not been studied [See Dosage and Administration (2.4), Clinical Pharmacology (12.3)]. 8.7 Renal Impairment 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 (12.3)].

Interactions

7 DRUG INTERACTIONS Protein-bound drugs: Monitor for adverse reactions and reduce dosage of ZOLOFT 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 5 includes clinically significant drug interactions with ZOLOFT [See Clinical Pharmacology (12.3)]. Table 5. Clinically-Significant Drug Interactions with ZOLOFT Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of SSRIs including ZOLOFT and MAOIs increases the risk of serotonin syndrome. Intervention: ZOLOFT 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 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 ZOLOFT is contraindicated [See Contraindications (4)]. Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs with ZOLOFT 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 ZOLOFT and/or concomitant serotonergic 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 and anticoagulants) Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with ZOLOFT may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of ZOLOFT 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 Drugs Highly Bound to Plasma Protein Clinical Impact: ZOLOFT is highly bound to plasma protein. The concomitant use of ZOLOFT with another drug that is highly bound to plasma protein may increase free concentrations of ZOLOFT or other tightly-bound drugs in plasma [See Clinical Pharmacology (12.3)]. Intervention: Monitor for adverse reactions and reduce dosage of ZOLOFT or other protein-bound drugs as warranted. Examples: warfarin Drugs Metabolized by CYP2D6 Clinical Impact: ZOLOFT is a CYP2D6 inhibitor [See Clinical Pharmacology (12.3)]. The concomitant use of ZOLOFT with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant ZOLOFT use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if ZOLOFT is discontinued. Examples: propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thoridazine, tolterodine, venlafaxine Phenytoin Clinical Impact: Phenytoin is a narrow therapeutic index drug. ZOLOFT may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating ZOLOFT. Reduce phenytoin dosage if needed. Examples: phenytoin, fosphenytoin 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 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.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). 7.2 Drugs Having No Clinically Important Interactions with ZOLOFT Based on pharmacokinetic studies, no dosage adjustment of ZOLOFT 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 ZOLOFT is administered concomitantly [See Clinical Pharmacology (12.3)]. 7.3 False-Positive Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking ZOLOFT. 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 ZOLOFT. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines.

More information

Category Value
Authorisation number NDA019839
Agency product number UTI8907Y6X
Orphan designation No
Product NDC 0049-4960,0049-4950,0049-4940,0049-4910,0049-4900
Date Last Revised 23-04-2018
Type HUMAN PRESCRIPTION DRUG
Storage and handling Store ZOLOFT at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
Marketing authorisation holder Roerig
Warnings WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [See Warnings and Precautions (5.1)]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients (5.1) Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors (5.1)