Zoloft/Zoloft ODT

Zoloft/Zoloft ODT

sertraline

Manufacturer:

Pfizer

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Sertraline HCl.
Action
Pharmacology: Pharmacodynamics: Sertraline is a potent and selective inhibitor of neuronal serotonin (5-HT) re-uptake in vitro which results in the potentiation of the effects of 5-HT in animals. It has only very weak effects on norepinephrine and dopamine neuronal re-uptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals. In controlled studies in normal volunteers, sertraline did not cause sedation and did not interfere with psychomotor performance. In accordance with its selective inhibition of 5-HT uptake, sertraline does not enhance catecholaminergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. The chronic administration of sertraline in animals was associated with down-regulation of brain norepinephrine receptors as observed with other clinically effective antidepressants and anti-obsessional drugs.
Sertraline has not demonstrated potential for abuse. In a placebo-controlled, double-blind, randomized study of the comparative abuse liability of sertraline, alprazolam and d-amphetamine in humans, sertraline did not produce positive subjective effects indicative of abuse potential. In contrast, subjects rated both alprazolam and d-amphetamine significantly greater than placebo on measures of drug liking, euphoria and abuse potential. Sertraline did not produce either the stimulation and anxiety associated with d-amphetamine or the sedation and psychomotor impairment associated with alprazolam. Sertraline does not function as a positive reinforcer in rhesus monkeys trained to self-administer cocaine, nor does it substitute as a discriminative stimulus for either d-amphetamine or pentobarbital in rhesus monkeys.
Clinical Trials: Major Depressive Disorder: A study was conducted which involved depressed outpatients who had responded by the end of an initial 8-week open treatment phase on sertraline 50-200 mg/day. These patients (N=295) were randomized to continuation for 44 weeks on double-blind sertraline 50-200 mg/day or placebo. A statistically significant lower relapse rate was observed for patients taking sertraline compared to those on placebo. The mean dose for completers was 70 mg/day.
Obsessive-Compulsive Disorder (OCD): In a long-term study, patients meeting DSM-III-R criteria for OCD who had responded during a 52-week single-blind trial on sertraline 50-200 mg/day (n=224) were randomized to continuation of sertraline or to substitution of placebo for up to 28 weeks of observation for discontinuation due to relapse or insufficient clinical response. Patients receiving continued sertraline treatment experienced a 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.
Panic Disorder: In a long-term study, patients meeting DSM-III-R criteria for panic disorder who had responded during a 52-week open trial on sertraline 50-200 mg/day (n=183) were randomized to continuation of sertraline or to substitution of placebo for up to 28 weeks of observation for discontinuation due to relapse or insufficient clinical response. Patients receiving continued sertraline treatment experienced a 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.
Post-Traumatic Stress Disorder (PTSD): In a long-term study, patients meeting DSM-III-R criteria for PTSD who had responded during a 24-week open trial on sertraline 50-200 mg/day (n=96) were randomized to continuation of sertraline or to substitution of placebo for up to 28 weeks of observation for relapse. Patients receiving continued sertraline treatment experienced significantly lower relapse rates over the subsequent 28 weeks compared to those receiving placebo. This pattern was demonstrated in male and female subjects.
Social Phobia (Social Anxiety Disorder): In a social phobia relapse prevention study, patients who were responders at the end of a 20-week, multicenter, flexible dose study that compared sertraline (50-200 mg/day) to placebo, were re-randomized for an additional 24 weeks to either sertraline continuation treatment (within 50-200 mg/day) or placebo substitution, while placebo responders remained on placebo. Patients receiving sertraline continuation treatment experienced a statistically significant lower relapse rate over this 24-week study than patients randomized to placebo substitution treatment.
Premenstrual Dysphoric Disorder (PMDD): The effectiveness of Zoloft for the treatment of PMDD was established in 2 double-blind, parallel group, placebo-controlled flexible dose trials (studies 1 and 2) conducted over 3 menstrual cycles. Patients in study 1 met DSM-III-R criteria for late luteal phase dysphoric disorder (LLPDD), the clinical entity now referred to as PMDD in DSM-IV. Patients in study 2 met DSM-IV criteria for PMDD. Study 1 utilized daily dosing throughout the study, while study 2 utilized luteal phase dosing for the 2 weeks prior to the onset of menses. The mean duration of PMDD symptoms for these patients was approximately 10.5 years in both studies. Patients on oral contraceptives were excluded from these trials; therefore, the efficacy of sertraline in combination with oral contraceptives for the treatment of PMDD is unknown.
Efficacy was assessed with the daily record of severity of problems (DRSP), a patient-rated instrument that mirrors the diagnostic criteria for PMDD as identified in the DSM-IV, and includes assessments for mood, physical symptoms and other symptoms. Other efficacy assessments included the Hamilton Depression Rating Scale (HAMD-17), and the Clinical Global Impression Severity of Illness (CGI-S) and Improvement (CGI-I) scores.
In study 1, involving n=251 randomized patients, Zoloft treatment was initiated at 50 mg/day and administered daily throughout the menstrual cycle. In subsequent cycles, patients were dosed in the range of 50-150 mg/day on the basis of clinical response and toleration. The mean dose for completers was 102 mg/day. Zoloft administered daily throughout the menstrual cycle was 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 2, involving n=281 randomized patients, Zoloft 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. In subsequent cycles, patients were dosed in the range of 50-100 mg/day in the luteal phase of each cycle, on the basis of clinical response and toleration. Patients who were titrated to 100 mg/day received 50 mg/day for the first 3 days of the cycle, then 100 mg/day for the remainder of the cycle. The mean Zoloft dose for completers was 74 mg/day. Zoloft administered in the late luteal phase of the menstrual cycle was 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.
There was insufficient information to determine the effect of race or age on outcome in these studies.
Pharmacokinetics: Sertraline exhibits dose proportional pharmacokinetics over the range of 50-200 mg. In man, following oral once-daily dosing over the range of 50-200 mg for 14 days, peak plasma concentrations (Cmax) of sertraline occur at about 4.5-8.4 hrs post-dosing. The pharmacokinetic profile in either adolescents or the elderly is not significantly different from that in adults between 18 and 65 years. The mean half-life of sertraline for young and elderly men and women ranges from 22-36 hrs. Consistent with the terminal elimination half-life, there is an approximately 2-fold accumulation up to steady-state concentrations, which are achieved after 1 week of once-daily dosing. Approximately 98% of the circulating drug is bound to plasma proteins. Animal studies indicate that sertraline has a large apparent volume of distribution. The pharmacokinetics of sertraline in pediatric OCD patients have been shown to be comparable with adults (although pediatric patients metabolize sertraline with slightly greater efficiency). However, lower doses may be advisable for pediatric patients, given their lower body weights (especially those patients 6-12 years), in order to avoid excessive plasma levels.
Sertraline undergoes extensive first-pass hepatic metabolism. The principal metabolite in plasma, N-desmethylsertraline, is substantially less active (about 20 times) than sertraline in vitro and there is no evidence of activity in in vivo models of depression. The half-life of N-desmethylsertraline is in the range of 62-104 hrs. Sertraline and N-desmethylsertraline are both extensively metabolized in man and the resultant metabolites excreted in feces and urine in equal amounts. Only a small amount (<0.2%) of unchanged sertraline is excreted in the urine.
Food does not significantly change the bioavailability of sertraline tablets.
Indications/Uses
Treatment of symptoms of depression including depression accompanied by symptoms of anxiety, in patients with or without a history of mania; obsessive-compulsive disorder (OCD), therapy is effective in preventing release of the initial episode of OCD.
Treatment of pediatric patients with OCD; panic disorder, with or without agoraphobia; post-traumatic stress disorder (PTSD); social phobia (social anxiety disorder).
Following satisfactory response, continuation with sertraline therapy is effective in preventing relapse of the initial episode of depression, or recurrence of further depressive episodes, OCD, panic disorder, PTSD or social phobia.
Treatment of premenstrual dysphoric disorder (PMDD). The essential features of PMDD include markedly depressed mood, anxiety or tension, affective lability and persistent anger or irritability. Other features include decreased interest in activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. These symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school or with usual social activities and relationships with others. In making the diagnosis, care should be taken to rule out other cyclical mood disorders that may be exacerbated by treatment with an antidepressant.
Dosage/Direction for Use
Sertraline should be administered once daily, either in the morning or evening. Sertraline tablets can be administered with or without food.
Initial Treatment: Depression and OCD: Sertraline treatment should be administered at a dose of 50 mg/day.
Panic Disorder, PTSD and Social Phobia: Therapy should be initiated at 25 mg/day. After 1 week, the dose should be increased to 50 mg once daily. This dosage regimen has been demonstrated to reduce the frequency of early treatment-emergent side effects characteristic of panic disorder.
Premenstrual Dysphoric Disorder: Treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of menstrual cycle, depending on physician assessment.
Titration: Depression, OCD, Panic Disorder and PTSD: Patients not responding to a 50-mg dose may benefit from dose increases.
Dose changes should be made at intervals of at least 1 week, up to a maximum of 200 mg/day. Changes in dose should not be made more frequently than once per week given the 24-hr elimination half-life of sertraline.
The onset of therapeutic effect may be seen within 7 days. However, longer periods are usually necessary to demonstrate therapeutic response, especially in OCD.
Premenstrual Dysphoric Disorder: Patients not responding to a 50-mg dose may benefit from dose increases (at 50-mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100-mg/day dose has been established with luteal phase dosing, a 50-mg/day titration step for 3 days should be utilized at the beginning of each luteal phase dosing period.
Maintenance: Dosage during long-term therapy should be kept at the lowest effective level, with subsequent adjustment depending on therapeutic response.
Children: The safety and efficacy of sertraline has been established in pediatric OCD patients 6-17 years. The administration of sertraline to pediatric OCD patients (13-17 years) should commence at 50 mg/day. Therapy for pediatric OCD patients (6-12 years) should commence at 25 mg/day increasing to 50 mg/day after 1 week. Subsequent doses may be increased in case of lack of response in 50-mg/day increments up to 200 mg/day as needed. In a clinical trial in patients 6-17 years with depression or OCD, sertraline appeared to have a similar pharmacokinetic profile to that found in adults. However, the generally lower body weights of children compared to those of adults should be taken into consideration when increasing the dose from 50 mg.
Titration in Children and Adolescents: Sertraline has an elimination half-life of approximately 1 day; dose changes should not occur at intervals of <1 week.
Elderly: The same dose range as in younger patients may be used in the elderly. Over 700 elderly patients (>65 years) have participated in clinical studies which demonstrated the efficacy of sertraline in this patient population. The pattern and incidence of adverse reactions in the elderly was similar to that in younger patients.
Patients with Hepatic Insufficiency: The use of sertraline in patients with hepatic disease should be approached with caution. A lower or less frequent dose should be used in patients with hepatic impairment (see Precautions).
Patients with Renal Insufficiency: Sertraline is extensively metabolized. Excretion of unchanged drug in urine is a minor route of elimination. As expected from the low renal excretion of sertraline, sertraline dosing does not have to be adjusted based on the degree of renal impairment (see Precautions).
Overdosage
On the evidence available, sertraline has a wide margin of safety in overdose. Overdoses of sertraline alone of up to 13.5 g have been reported. Deaths have been reported involving overdoses of sertraline, primarily in combination with other drugs and/or alcohol. Therefore, any overdosage should be treated aggressively. Symptoms of overdose include serotonin-mediated side effects eg, somnolence, gastrointestinal disturbances (eg, nausea and vomiting), tachycardia, tremor, agitation and dizziness. Less frequently reported was coma.
There are no specific antidotes to sertraline. Establish and maintain an airway and insure adequate oxygenation and ventilation, if necessary. Activated charcoal, which may be used with a cathartic, may be as or more effective than lavage, and should be considered in treating overdose. Induction of emesis is not recommended. Cardiac and vital sign monitoring is recommended, along with general symptomatic and supportive measures. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
Contraindications
Patients with a known hypersensitivity to sertraline.
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) (see Precautions) or pimozide (see Interactions).
Special Precautions
Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS): The development of potentially life-threatening syndromes eg, SS or NMS has been reported with SSRIs, including treatment with sertraline. The risk of SS or NMS with SSRIs is increased with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), antipsychotics and other dopamine antagonists. SS symptoms may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). Some signs of SS, including hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes resemble NMS. Patients should be monitored for the emergence of signs and symptoms of SS or NMS syndrome (see Contraindications).
MAOIs: Cases of serious reactions, sometimes fatal, have been reported in patients receiving sertraline in combination with a MAOI, including the selective MAOI, selegiline, the reversible MAOI, moclobemide and MAOI drugs eg, linezolid. Some cases presented with features resembling the serotonin syndrome, symptoms of which include, hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma. Therefore, sertraline should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should elapse after discontinuing sertraline treatment before starting a MAOI (see Contraindications).
Other Serotonergic Drugs: Co-administration of sertraline with other drugs which enhance the effects of serotonergic neurotransmission eg, tryptophan, fenfluramine, 5-HT agonists or the herbal medicine St. John's wort (Hypericum perforatum) should be undertaken with caution and avoided whenever possible due to the potential for pharmacodynamic interaction.
Switching from SSRIs, Antidepressants or Anti-Obsessional Drugs: There is limited controlled experience regarding the optimal timing of switching from SSRIs, antidepressants or anti-obsessional drugs to sertraline. Care and prudent medical judgement should be exercised when switching, particularly from long-acting agents eg, fluoxetine. The duration of a washout period for switching from one SSRI to another has not been established.
Activation of Mania/Hypomania: During premarketing testing, hypomania or mania occurred in approximately 0.4% of sertraline-treated patients. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder treated with other marketed antidepressant and anti-obsessional drugs.
Seizures: Seizures are a potential risk with antidepressant and anti-obsessional drugs. Seizures were reported in approximately 0.08% of patients treated with sertraline in the development program for depression. No seizures were reported in patients treated with sertraline in the development program for panic. During the development program for OCD, 4 out of approximately 1800 patients exposed to sertraline experienced seizures (approximately 0.2%). Three of these patients were adolescents, 2 with a seizure disorder and 1 with a family history of seizure disorder, none of whom were receiving anticonvulsant medication. In all these cases, the relationship to sertraline therapy was uncertain. Since sertraline has not been evaluated in patients with a seizure disorder, it should be avoided in patients with unstable epilepsy; patients with controlled epilepsy should be carefully monitored. Sertraline should be discontinued in any patient who develops seizures.
Suicide: Since the possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs, patients should be closely supervised during the early course of therapy.
Abnormal Bleeding/Hemorrhage: There have been reports of cutaneous bleeding abnormalities eg, ecchymoses and purpura with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (eg, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) as well as in patients with a history of bleeding disorders (see Interactions).
Hyponatremia: Hyponatremia may occur as a result of treatment with SSRIs or SNRIs including sertraline. In many cases, hyponatremia appears to be the result of a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases of serum sodium levels <110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also patients taking diuretics or who are otherwise volume-depleted may be at greater risk (see Elderly under Dosage & Administration). Discontinuation of sertraline should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness and unsteadiness which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest and death.
Because of the well-established comorbidity between OCD and depression, panic disorder and depression, PTSD and depression, and social phobia and depression, the same precautions observed when treating patients with depression should be observed when treating patients with OCD, panic disorder, PTSD or social phobia.
Use in Hepatic Insufficiency: Sertraline is extensively metabolized by the liver. A multiple-dose pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a prolonged elimination half-life and approximately 3-fold greater AUC and Cmax in comparison to normal subjects. There were no significant differences in plasma protein-binding observed between the 2 groups. The use of sertraline in patients with hepatic disease must be approached with caution. A lower or less frequent dose should be used in patients with hepatic impairment.
Use in Renal Insufficiency: Sertraline is extensively metabolized. Excretion of unchanged drug in urine is a minor route of elimination. In studies of patients with mild to moderate renal impairment (creatinine clearance 30-60 mL/min) or moderate to severe renal impairment (creatinine clearance 10-29 mL/min), multiple-dose pharmacokinetic parameters (AUC0-24 or Cmax) were not significantly different compared with controls. Half-lives were similar and there were no differences in plasma protein-binding in all groups studied. This study indicates that, as expected from the low renal excretion of sertraline, sertraline dosing does not have to be adjusted based on the degree of renal impairment.
Effects on the Ability to Drive or Operate Machinery: Clinical pharmacology studies have shown that sertraline has no effect on psychomotor performance. However, as psychotropic drugs may impair the mental or physical abilities required for the performance of potentially hazardous tasks eg, driving a car or operating machinery, the patient should be cautioned accordingly.
Use in pregnancy & lactation: Reproduction studies have been performed in rats and rabbits at doses up to approximately 20 and 10 times the maximum daily human mg/kg dose, respectively. There was no evidence of teratogenicity at any dose level. At the dose level corresponding to approximately 2.5-10 times the maximum daily human mg/kg dose, however, sertraline was associated with delayed ossification in fetuses, probably secondary to effects on the dams.
There was decreased neonatal survival following maternal administration of sertraline at doses approximately 5 times the maximum human mg/kg dose. Similar effects on neonatal survival have been described for other antidepressant drugs. The clinical significance of these effects is unknown.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sertraline should be used during pregnancy only if the perceived benefits outweigh the risks.
Isolated studies in small numbers of nursing mothers and their infants indicated negligible or undetectable levels of sertraline in infant serum, although levels in breast milk were more concentrated than in maternal serum. Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk.
If sertraline is used during pregnancy and/or lactation, the physician should be aware of post-marketing reports of symptoms, including those compatible with withdrawal reactions, in some neonates whose mothers had been on SSRI antidepressants, including sertraline.
Women of childbearing potential should employ an adequate method of contraception if taking sertraline.
Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). Pulmonary hypertension of the newborn occurs in 1-2 per 1000 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 6-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".
Use In Pregnancy & Lactation
Reproduction studies have been performed in rats and rabbits at doses up to approximately 20 and 10 times the maximum daily human mg/kg dose, respectively. There was no evidence of teratogenicity at any dose level. At the dose level corresponding to approximately 2.5-10 times the maximum daily human mg/kg dose, however, sertraline was associated with delayed ossification in fetuses, probably secondary to effects on the dams.
There was decreased neonatal survival following maternal administration of sertraline at doses approximately 5 times the maximum human mg/kg dose. Similar effects on neonatal survival have been described for other antidepressant drugs. The clinical significance of these effects is unknown.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sertraline should be used during pregnancy only if the perceived benefits outweigh the risks.
Isolated studies in small numbers of nursing mothers and their infants indicated negligible or undetectable levels of sertraline in infant serum, although levels in breast milk were more concentrated than in maternal serum. Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk. If sertraline is used during pregnancy and/or lactation, the physician should be aware of post-marketing reports of symptoms, including those compatible with withdrawal reactions, in some neonates whose mothers had been on SSRI antidepressants, including sertraline.
Women of childbearing potential should employ an adequate method of contraception if taking sertraline.
Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). Pulmonary hypertension of the newborn occurs in 1-2 per 1000 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 6-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".
Adverse Reactions
Clinical Trial Data: Side effects which occurred significantly more frequently with sertraline than with placebo in multiple-dose studies for depression were: Gastrointestinal Disorders: Diarrhea/loose stools, dry mouth, dyspepsia and nausea.
Metabolism and Nutrition Disorders: Anorexia.
Nervous System Disorders: Dizziness, somnolence and tremor.
Psychiatric Disorders: Insomnia.
Reproductive System and Breast Disorders: Sexual dysfunction (principally ejaculatory delay in males).
Skin and Subcutaneous Tissue Disorders: Increased sweating.
The side effect profile commonly observed in double-blind, placebo-controlled studies in patients with OCD, panic disorder, PTSD and social phobia was similar to that observed in clinical trials in patients with depression.
Post-Marketing Data: Voluntary reports of adverse events in patients receiving sertraline since market introduction have been received. They include the following: Blood and Lymphatic System Disorders: Leucopenia and thrombocytopenia.
Cardiac Disorders: Palpitations and tachycardia.
Ear and Labyrinth Disorders: Tinnitus.
Endocrine Disorders: Hyperprolactinemia, hypothyroidism and SIADH secretion.
Eye Disorders: Mydriasis and abnormal vision.
Gastrointestinal Disorders: Abdominal pain, constipation, pancreatitis and vomiting.
General Disorders and Administration Site Conditions: Asthenia, chest pain, peripheral edema, fatigue, fever and malaise.
Hepatobiliary Disorders: Serious liver events (including hepatitis, jaundice and liver failure) and asymptomatic elevations in serum transaminases (SGOT and SGPT).
Immune System Disorders: Allergic reaction, allergy and anaphylactoid reaction.
Investigations: Abnormal clinical laboratory results, altered platelet function, increased serum cholesterol, decreased or increased weight.
Metabolism and Nutrition Disorders: Increased appetite and hyponatremia.
Musculoskeletal and Connective Tissue Disorders: Arthralgia and muscle cramps.
Nervous System Disorders: Coma, convulsions, headache, hypoesthesia, migraine, movement disorders (including extrapyramidal symptoms eg, hyperkinesia, hypertonia, teeth grinding or gait abnormalities), involuntary muscle contractions, paresthesia and syncope. Also reported were signs and symptoms associated with serotonin syndrome. In some cases associated with concomitant use of serotonergic drugs that included agitation, confusion, diaphoresis, diarrhea, fever, hypertension, rigidity and tachycardia.
Psychiatric Disorders: Aggressive reaction, agitation, anxiety, depressive symptoms, euphoria, hallucination, decreased libido in both (males and females), paroniria and psychosis.
Renal and Urinary Disorders: Enuresis, urinary incontinence and urinary retention.
Reproductive System and Breast Disorders: Galactorrhea, gynecomastia, menstrual irregularities and priapism.
Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm and yawning.
Skin and Subcutaneous Tissue Disorders: Alopecia, angioedema, face edema, periorbital edema, photosensitivity skin reaction, pruritus, purpura, rash (including rare reports of serious exfoliative skin disorders eg, Stevens-Johnson syndrome and epidermal necrolysis) and urticaria.
Vascular Disorders: Abnormal bleeding (eg, epistaxis, gastrointestinal bleeding or hematuria), hot flushes and hypertension.
Other: Symptoms following the discontinuation of sertraline have been reported and included agitation, anxiety, dizziness, headache, nausea and paresthesia.
Drug Interactions
MAOIs: See Contraindications and Precautions.
Pimozide: Increased pimozide levels have been demonstrated in a study of a single low dose pimozide (2 mg) with sertraline co-administration. These increased levels were not associated with any changes in EKG. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant administration of sertraline and pimozide is contraindicated.
CNS Depressants and Alcohol: The co-administration of sertraline 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.
Lithium: In placebo-controlled trials in normal volunteers, the co-administration of sertraline with lithium did not significantly alter lithium pharmacokinetics, but did result in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. When co-administering sertraline with medications eg, lithium, which may act via serotonergic mechanisms, patients should be appropriately monitored.
Phenytoin: Placebo-controlled trials in normal volunteers suggest that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy, with appropriate adjustments to the phenytoin dose. In addition, co-administration of phenytoin may cause a reduction of sertraline plasma levels.
Sumatriptan: There have been rare post-marketing reports describing patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan. If concomitant treatment with sertraline and sumatriptan is clinically warranted, appropriate observation of the patient is advised (see Other Serotonergic Drugs under Precautions).
Other Serotonergic Drugs: See Precautions.
Protein-Bound Drugs: Since sertraline is bound to plasma proteins, the potential of sertraline to interact with other plasma protein-bound drugs should be borne in mind. However, in 3 formal interaction studies with diazepam, tolbutamide and warfarin, respectively, sertraline was not shown to have significant effects on the protein binding of the substrate (see Warfarin and Other Drug Interactions as follows).
Warfarin: Co-administration of sertraline 200 mg daily with warfarin resulted in a small but statistically significant increase in prothrombin time, the clinical significance of which is unknown. Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or stopped.
Other Drug Interactions: Formal drug interaction studies have been performed with sertraline. Co-administration of sertraline 200 mg daily with diazepam or tolbutamide resulted in small, statistically significant changes in some pharmacokinetic parameters. Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline had no effect on the β-adrenergic-blocking ability of atenolol. No interaction of sertraline 200 mg daily was observed with glibenclamide or digoxin.
Electroconvulsive Therapy (ECT): There are no clinical studies establishing the risks or benefits of the combined use of ECT and sertraline.
Drugs Metabolized by Cytochrome P-450 (CYP)2D6: There is variability among antidepressants in the extent to which they inhibit the activity of isozyme CYP 2D6. The clinical significance of this depends on the extent of the inhibition and the therapeutic index of the co-administered drug. CYP 2D6 substrates with a narrow theapeutic index include TCAs and class 1C antiarrhythmics eg, propafenone and flecainide. In formal interaction studies, chronic dosing with sertraline 50 mg daily showed minimal elevation (mean 23-37%) of steady-state desipramine plasma levels (a marker of CYP 2D6 isoenzyme activity).
Drugs Metabolized by Other CYP Enzymes (CYP 3A3/4, CYP 2C9, CYP 2C19, CYP 1A2) CYP 3A3/4: In vivo interaction studies have demonstrated that chronic administration of sertraline 200 mg daily does not inhibit the CYP 3A3/4-mediated 6-β hydroxylation of endogenous cortisol or the metabolism of carbamazepine or terfenadine. In addition, the chronic administration of sertraline 50 mg daily does not inhibit the CYP 3A3/4-mediated metabolism of alprazolam. The data suggest that sertraline is not a clinically relevant inhibitor of CYP 3A3/4.
CYP 2C9: The apparent lack of clinically significant effects of the chronic administration of sertraline 200 mg daily on plasma concentrations of tolbutamide, phenytoin and warfarin suggests that sertraline is not a clinically relevant inhibitor of CYP 2C9 (see Other Drug Interactions, Phenytoin and Warfarin).
CYP 2C19: The apparent lack of clinically significant effects of the chronic administration of sertraline 200 mg daily on plasma concentrations of diazepam suggests that sertraline is not a clinically relevant inhibitor of CYP 2C19 (see Other Drug Interactions).
CYP 1A2: In vitro studies indicate that sertraline has little or no potential to inhibit CYP 1A2.
MIMS Class
ATC Classification
N06AB06 - sertraline ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
Presentation/Packing
FC tab 50 mg x 60's. 100 mg x 30's. ODT Tab 50 mg x 30's.
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