Sertraline Brand name: Zoloft

Drug monograph

Contents

• Summary
• Pharmacology
• Indications
• Contraindications
• Warnings
• Precautions
• Adverse Effects
• Overdose
• Dosage
• Supplied
• Research

Summary

ZOLOFT Pfizer
Sertraline HCI

Use:
SSRI. Depression: Patients > 18 years of age: Initially, 50 mg once daily; increase dosage gradually, if needed, at 1-week intervals. Maximum: 200 mg/day. Maintenance: lowest effective dose.

Panic disorder: 25 mg once daily and increase, if necessary, by 50 mg increments at intervals of no less than 1 week, to a maximum of 200 mg/day.

Obsessive-compulsive disorder (OCD): Initially, 50 mg/day. Thereafter, increase the dosage, if necessary, by 50 mg increments, over several weeks or months, to a maximum of 200 mg/day.

Zoloft's effectiveness for more than 12 weeks of therapy in panic disorder and OCD not yet established.

Contraindications:
Not to be use with an MAOI or within 14 days of starting or discontinuing MAOI therapy. Concomitant use with pimozide.

Precautions:
Pregnancy, lactation, patients< 18 years of age. Seizure disorders, a history of drug abuse, renal or hepatic impairment. Activation of mania/hypomania, suicidal tendency, concomitant illnesses that could affect metabolism or hemodynamic responses. Rare reports of altered platelet function; hyponatremia, possibly due to the syndrome of inappropriate antidiuretic hormone secretion.

Side effects:
Nausea, diarrhea/loose stools, dyspepsia, male sexual dysfunction (primarily ejaculatory delay), insomnia, somnolence, tremor, increased sweating, dry mouth, dizziness.

Interactions:
See Contraindications. Use cautiously with CNS-active drugs; serotonergic drugs, such as fenfluramine, should not be used with sertraline. Hypoglycemic agents, drugs highly bound to plasma proteins, cimetidine (may decrease clearance of sertraline). Warfarin (monitor PT). St. John's Wort (increase in undesirable effects).

Patient tips:
Full therapeutic effect may be delayed until 4 or more weeks of treatment. Take capsules with food once daily, preferably with evening meal or breakfast. May cause dizziness (NB driving). Restrict alcohol intake.

Supplied:
25 mg, 50 mg, 100mg capsules.

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Pharmacology

Antidepressant

The antidepressant effect of sertraline is presumed to be linked to its ability to inhibit the neuronal reuptake of serotonin. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets.

Like most clinically effective antidepressants, sertraline downregulates brain norepinephrine and serotonin receptors in animals. In receptor binding studies, sertraline has no significant affinity for adrenergic (alpha(1), alpha(2) and beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, 5-HT2) or benzodiazepine binding sites.

In placebo-controlled studies in normal volunteers, sertraline did not cause sedation and did not interfere with psychomotor performance.

Pharmacokinetics:
Following multiple oral once-daily doses of 200 mg, the mean peak plasma concentration (C(max)) of sertraline is 0.19 mcg/mL occurring between 6 to 8 hours post-dose. The area under the plasma concentration time is 2.8 mg hr/L. For desmethylsertraline, C(max) is 0.14 mcg/mL, the half-life 65 hours and the area under the curve 2.3 mg hr/L. Following single or multiple oral once-daily doses of 50 to 400 mg/day the average terminal elimination half-life is approximately 26 hours. Linear dose proportionality has been demonstrated over the clinical dose range of 50 to 200 mg/day.

Food appears to increase the bioavailability by about 40%: it is recommended that sertraline be administered with meals.

Sertraline is extensively metabolized to N-desmethylsertraline, which shows negligible pharmacological activity. Both sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation and glucuronide conjugation. Biliary excretion of metabolites is significant.

Approximately 98% of sertraline is plasma protein bound. The interactions between sertraline and other highly protein bound drugs have not been fully evaluated (see Precautions).

The pharmacokinetics of sertraline itself appear to be similar in young and elderly subjects. Plasma levels of N-desmethylsertraline show a 3-fold elevation in the elderly following multiple dosing, however, the clinical significance of this observation is not known.

Liver and Renal Disease:
The pharmacokinetics of sertraline in patients with significant hepatic or renal dysfunction have not been determined.

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Indications

For the symptomatic relief of depressive illness. However, the antidepressant action of sertraline in hospitalized depressed patients has not been adequately studied.

A placebo-controlled European study carried out over 44 weeks, in patients who were responders to sertraline has indicated that sertraline may be useful in continuation treatment, suppressing reemergence of depressive symptoms.

However, because of methodological limitations, these findings on continuation treatment have to be considered tentative at this time.

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Contraindications

Patients with known hypersensitivity to the drug.

No clinical data are available on the effects of the combined use of sertraline and MAO inhibitors; therefore, sertraline should not be administered together with MAO inhibitors. At least 14 days should elapse between the discontinuation of an MAO inhibitor and the initiation of treatment with sertraline, as well as between the discontinuation of sertraline and the initiation of treatment with an MAO inhibitor. Administration at shorter intervals may increase the risk of serious events.

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Warnings

None.

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Precautions

Activation of Mania/Hypomania:
During clinical testing in depressed patients, hypomania or mania occurred in approximately 0.6% 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 antidepressants.

Seizure:
Sertraline has not been evaluated in patients with seizure disorders. These patients were excluded from clinical studies during the product's premarket testing. Accordingly, sertraline should be introduced with care in epileptic patients.

Suicide:
The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Therefore, high risk patients should be closely supervised throughout therapy and consideration should be given to the possible need for hospitalization. In order to minimize the opportunity for overdosage, prescriptions for sertraline should be written for the smallest quantity of drug consistent with good patient management.

Occupational Hazards:
Any psychoactive drug may impair judgment, thinking, or motor skills, and patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that the drug treatment does not affect them adversely.

Patients with Concomitant Illness:
General:
Clinical experience with sertraline in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using sertraline in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Cardiac Disease:
Sertraline has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.

The electrocardiograms of 598 patients who received sertraline were compared in a blinded fashion to the electrocardiograms of 244 placebo patients and 206 amitriptyline patients. The data indicate that sertraline is not associated with the development of significant ECG abnormalities.

Effect on Blood Pressure:
The frequency of clinically noticeable changes (+/-15 to 20 mm Hg) in blood pressure in placebo controlled studies was similar for patients being treated with sertraline or placebo (see Table I).

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Table I
Percentage of Patients with Noticeable Changes in Blood Pressure
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                 Change                      Numbers and % of Patients
               Relative to   Numbers Tested     with Specified Change
Parameter       Baseline   Sertraline Placebo  Sertraline  Placebo
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Standing        increase      703       358    13    1.8%   3  0.8%
 Systolic BP    decrease                       31    4.4%  16  4.5%
Standing        increase      703       358    20    2.8%  13  3.6%
 Diastolic BP   decrease                       28    4.0%  12  3.4%
Supine          increase      706       362    15    2.1%   6  1.7%
 Systolic BP    decrease                       19    2.7%   7  1.9%
Supine          increase      706       362    16    2.3%   7  1.9%
 Diastolic BP   decrease                       18    2.5%   4  1.1%
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Hepatic Dysfunction:
Sertraline is extensively metabolized by the liver. The pharmacokinetics and therapeutic efficacy of sertraline have not been studied in patients with significant hepatic dysfunction. Accordingly, it should be used with caution in such patients.

Renal Dysfunction:
Sertraline is extensively metabolized and excretion of unchanged drug in the urine is a minor route of elimination. The pharmacokinetics of sertraline have not been studied in patients with renal impairment and, until adequate numbers of patients with mild, moderate or severe renal impairment have been evaluated during chronic treatment with sertraline, it should be used with caution in such patients.

Carcinogenesis:
In carcinogenicity studies in CD-1 mice, sertraline at doses up to 40 mg/kg produces a dose related increase in the incidence of liver adenomas in male mice. Liver adenomas have a very variable rate of spontaneous occurrence in the CD-1 mouse. The clinical significance of these findings is unknown.

Pregnancy and Lactation:
The safety of sertraline during pregnancy and lactation has not been established and therefore, it should not be used in women of childbearing potential or nursing mothers, unless, in the opinion of the physician, the potential benefits to the patient outweigh the possible hazards to the fetus.

Labor and Delivery:
The effect of sertraline on labor and delivery in humans is unknown.

Children:
The safety and effectiveness of sertraline in children below the age of 18 have not been established.

Geriatrics:
462 elderly patients (>=65 years) have participated in multiple dose therapeutic studies with sertraline. The pattern of adverse reactions in the elderly was comparable to that in younger patients.

Drug Interactions:
Co-Administration of Drugs Highly Bound to Plasma Proteins:
Because sertraline is highly bound to plasma proteins, the co-administration of other highly bound drugs such as warfarin or digitoxin may cause a shift in plasma concentrations potentially resulting in adverse effects. At this time, the effect of sertraline on the anticoagulant activity of warfarin is unknown. Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or discontinued. Conversely, adverse effects may result from displacement of protein bound sertraline by other tightly bound drugs.

CNS Active Drugs:
The risk of using sertraline in combination with other CNS active drugs has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of sertraline and such drugs is required.

Co-administration with tryptophan may lead to a high incidence of serotonin-associated side effects. There is no experience with the concomitant use of sertraline and tryptophan in depressed patients.

In placebo-controlled trials in normal volunteers, the combined administration of lithium and sertraline did not alter the pharmacokinetics of sertraline. There is, however, no clinical experience with sertraline in lithium treated patients. Therefore, it is recommended that plasma lithium levels be monitored following initiation of sertraline therapy, so that appropriate adjustments to the lithium dose may be made if necessary. Co-administration with lithium may lead to a high incidence of serotonin-associated side effects.

Electroconvulsive Therapy:
There are no clinical studies with the combined use of electroconvulsive therapy (ECT) and sertraline.

Alcohol:
Although sertraline did not potentiate the cognitive and psychomotor effects of alcohol in experiments with normal subjects, the concomitant use of sertraline and alcohol in depressed patients has not been studied and is not recommended.

Hypoglycemic Drugs:
There are no controlled clinical trials with sertraline in diabetic patients treated with insulin or oral hypoglycemic drugs.

In a placebo-controlled trial in normal volunteers, the administration of sertraline for 22 days (dose was 200 mg/day for the final 13 days), caused a statistically significant 16% decrease in the clearance of tolbutamide following an i.v. dose of 1000 mg.

Hypoglycemia requiring dextrose infusion was observed in one patient treated with sertraline, glibenclamide, haloperidol, bisacodyl, ASA and flucloxacillin. The causal relationship to sertraline treatment was not firmly established. Nevertheless, close monitoring of glycemia in patients treated with sertraline and oral hypoglycemic drugs or insulin is recommended.

Beta Blockers:
There is no experience with the use of sertraline in hypertensive patients controlled by beta-blockers. In a placebo-controlled crossover study in normal volunteers, the effect of sertraline on the beta-adrenergic blocking activity of atenolol was assessed. The mean CD25's (the doses of isoproterenol required to increase heart rate by 25 bpm, the chronotropic dose 25 or CD25) and the average decreases in heart rate seen with atenolol during exercise test were not statistically different in the sertraline versus the placebo group. These data suggest that sertraline does not alter the beta-blocking action of atenolol.

Cimetidine:
In a placebo-controlled crossover study in normal volunteers, the potential of cimetidine to alter the disposition of a single 100 mg dose of sertraline was assessed. The mean sertraline C(max) and AUC were significantly higher in the cimetidine-treated group, as were the mean desmethylsertraline T(max) and AUC. These data suggest that concomitant administration of cimetidine may inhibit the metabolism of sertraline and its metabolite, desmethylsertraline, and may result in a decrease in the clearance and first pass metabolism of sertraline, with a possible increase in drug-related side effects.

Microsomal Enzyme Induction:
Sertraline was shown to induce hepatic enzymes as determined by the decrease of the antipyrine half-life. This degree of induction reflects a clinically insignificant change in hepatic metabolism.

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Adverse Effects

In clinical development programs, sertraline has been evaluated in 1902 subjects with depression. The most commonly observed adverse events associated with the use of sertraline were: gastrointestinal complaints, including nausea, diarrhea/loose stools and dyspepsia; male sexual dysfunction (primarily ejaculatory delay); insomnia and somnolence; tremor; increased sweating and dry mouth; and dizziness. In the fixed dose placebo controlled study, the overall incidence of side effects was dose related with a majority occurring in the patients treated with 200 mg dose.

The discontinuation rate due to adverse events was 15% in 2710 subjects who received sertraline in premarketing multiple dose clinical trials. The more common events (reported by at least 1% of subjects) associated with discontinuation included agitation, insomnia, male sexual dysfunction (primarily ejaculatory delay), somnolence, dizziness, headache, tremor, anorexia, diarrhea/loose stools, nausea and fatigue.

Incidence in Controlled Clinical Trials:
Table II enumerates adverse events that occurred at a frequency of 1% or more among sertraline patients who participated in controlled trials comparing titrated sertraline with placebo.

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Table II
Treatment-Emergent Adverse Experience Incidence in
Placebo-Controlled Clinical Trials*
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                       Percent of Patients Reporting
                         Zoloft   Placebo  Difference
Adverse Experience       (N=861)  (N=853)  Percentage
Autonomic Nervous System Disorders
 Mouth Dry                 16.3     9.3      7.0
 Sweating Increased         8.4     2.9      5.5
Cardiovascular
 Palpitations               3.5     1.6      1.9
 Chest Pain                 1.0     1.6     -0.6
Central and Peripheral Nervous System Disorders
 Headache                  20.3     19.0     1.3
 Dizziness                 11.7      6.7     5.0
 Tremor                    10.7      2.7     8.0
 Paresthesia                2.0      1.8     0.2
 Hypoesthesia               1.7      0.6     1.1
 Twitching                  1.4      0.1     1.3
 Hypertonia                 1.3      0.4     0.9
Disorders of Skin and Appendages
 Rash                       2.1      1.5     0.6
Gastrointestinal Disorders
 Nausea                    26.1     11.8    14.3
 Diarrhea/Loose Stools     17.7      9.3     8.4
 Constipation               8.4      6.3     2.1
 Dyspepsia                  6.0      2.8     3.2
 Vomiting                   3.8      1.8     2.0
 Flatulence                 3.3      2.5     0.8
 Anorexia                   2.8      1.6     1.2
 Abdominal Pain             2.4      2.2     0.2
 Appetite Increased         1.3      0.9     0.4
General
 Fatigue                   10.6      8.1     2.5
 Hot Flushes                2.2      0.5     1.7
 Fever                      1.6      0.6     1.0
 Back Pain                  1.5      0.9     0.6
Metabolic and Nutritional Disorders
 Thirst                     1.4      0.9     0.5
Musculo-Skeletal System Disorders
 Myalgia                    1.7      1.5     0.2
Psychiatric Disorders
 Insomnia                  16.4      8.8     7.6
 Sexual Dysfunction-
  Male (1)                 15.5      2.2    13.3
 Somnolence                13.4      5.9     7.5
 Agitation                  5.6      4.0     1.6
 Nervousness                3.4      1.9     1.5
 Anxiety                    2.6      1.3     1.3
 Yawning                    1.9      0.2     1.7
 Sexual Dysfunction-
  Female (2)                1.7      0.2     1.5
 Concentration Impaired     1.3      0.5     0.8
Reproduction
 Menstrual Disorder (2)     1.0      0.5     0.5
Respiratory System Disorders
 Rhinitis                   2.0      1.5     0.5
 Pharyngitis                1.2      0.9     0.3
pecial Senses
 Vision Abnormal            4.2      2.1     2.1
 Tinnitus                   1.4      1.1     0.3
 Taste Perversion           1.2      0.7     0.5
Urinary System Disorders
 Micturition Frequency      2.0      1.2     0.8
 Micturition Disorder       1.4      0.5     0.9
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 *Events reported by at least 1% of patients treated with
 Zoloft are included.
 (1)% based on male patients only: 271 Zoloft and 271 placebo
    patients. Male sexual dysfunction can be broken down into
    the categories of decreased libido, impotence and ejaculatory
    delay. In this data set, the percentages of males in the
    Zoloft group with these complaints are 4.8%, 4.8% and 8.9%,
    respectively. It should be noted that since some Zoloft
    patients reported more than one category of male sexual
    dysfunction, the incidence of each category of male sexual
    dysfunction combined is larger than the incidence for the
    general category of male sexual dysfunction, in which each
    patient is counted only once.
 (2)% based on female patient only: 590 Zoloft and 582 placebo
    patients.
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Other events observed during the premarketing evaluation of sertraline:
During its premarketing assessment, multiple doses of sertraline were administered to 2710 subjects. The conditions and duration of exposure to sertraline varied greatly, and included (in overlapping categories) clinical pharmacology studies, open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies, and studies for indications other than depression. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

All events are included except those already listed in Table II or in the Precautions section, and those reported in terms so general as to be uninformative. It is important to emphasize that although the events reported occurred during treatment with sertraline, they were not necessarily caused by it.

Autonomic Nervous System Disorders:
Infrequent: Flushing, mydriasis, increased saliva, cold clammy skin. Rare: Pallor.

Cardiovascular:
Infrequent: Postural dizziness, hypertension, hypotension, postural hypotension, edema, dependent edema, periorbital edema, peripheral edema, peripheral ischemia, syncope, tachycardia. Rare: Precordial chest pain, substernal chest pain, aggravated hypertension, myocardial infarction, varicose veins.

Central and Peripheral Nervous System Disorders:
Frequent: Confusion. Infrequent: Ataxia, abnormal coordination, abnormal gait, hyperesthesia, hyperkinesia, hypokinesia, migraine, nystagmus, vertigo. Rare: Local anesthesia, coma, convulsions, dyskinesia, dysphonia, hyporeflexia, hypotonia, ptosis.

Disorders of Skin and Appendages:
Infrequent: Acne, alopecia, pruritus, erythematous rash, maculopapular rash, dry skin. Rare: Bullous eruption, dermatitis, erythema multiforme, abnormal hair texture, hypertrichosis, photosensitivity reaction, follicular rash, skin discoloration, abnormal skin odor, urticaria.

Endocrine Disorders:
Rare: Exophthalmos, gynecomastia.

Gastrointestinal Disorders:
Infrequent: Dysphagia, eructation. Rare: Diverticulitis, fecal incontinence, gastritis, gastroenteritis, glossitis, gum hyperplasia, hemorrhoids, hiccup, melena, hemorrhagic peptic ulcer, proctitis, stomatitis, ulcerative stomatitis, tenesmus, tongue edema, tongue ulceration.

General:
Frequent: Asthenia. Infrequent: Malaise, generalized edema, rigors, weight decrease, weight increase. Rare: Enlarged abdomen, halitosis, otitis media, aphthous stomatitis.

Hematopoietic and Lymphatic:
Infrequent: Lymphadenopathy, purpura. Rare: Anemia, anterior chamber eye hemorrhage.

Metabolic and Nutritional Disorders:
Rare: Dehydration, hypercholesterolemia, hypoglycemia.

Musculo-Skeletal System Disorders:
Infrequent: Arthralgia, arthrosis, dystonia, muscle cramps, muscle weakness. Rare: Hernia.

Psychiatric Disorders:
Infrequent: Abnormal dreams, aggressive reaction, amnesia, apathy, delusion, depersonalization, depression, aggravated depression, emotional lability, euphoria, hallucination, neurosis, paranoid reaction, suicide attempt (including suicidal ideation), teeth-grinding, abnormal thinking. Rare: Hysteria, somnambulism withdrawal syndrome.

Reproductive:
Infrequent: Dysmenorrhea (2), intermenstrual bleeding (2). Rare: Amenorrhea (2), balanoposthitis (1), breast enlargement (2), female breast pain (2), leukorrhea (2), menorrhagia (2), atrophic vaginitis (2).

(1) - % based on male subjects only: 1005
(2) - % based on female subjects only: 1705

Respiratory System Disorders:
Infrequent: Bronchospasm, coughing, dyspnea, epistaxis. Rare: Bradypnea, hyperventilation, sinusitis, stridor.

Special Senses:
Infrequent: Abnormal accommodation, conjunctivitis, diplopia, earache, eye pain, xerophthalmia. Rare: Abnormal lacrimation, photophobia, visual field defect.

Urinary System Disorders:
Infrequent: Dysuria, face edema, nocturia, polyuria, urinary incontinence. Rare: Oliguria, renal pain, urinary retention.

Laboratory Tests:
In man, asymptomatic elevations in serum hepatic transaminases [AST (SGOT) and ALT (SGPT)] to a value >=3 times the upper limit of normal have been reported infrequently (approximately 0.6% and 1.1%, respectively) in association with sertraline administration. The proportion of patients having these elevations was greater in the sertraline group than in the placebo group. These hepatic enzyme elevations usually occurred within the first 1 to 9 weeks of drug treatment and promptly diminished upon drug discontinuation.

Sertraline therapy was associated with small mean increases in total cholesterol (approximately 3%) and triglycerides (approximately 5%), and a small mean decrease in serum uric acid (approximately 7%) of no apparent clinical importance.

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Overdose

Symptoms and Treatment:
Human Experience:
There have been 3 cases of sertraline overdosage (approximately 4 to 10 times the maximum recommended daily dose). These 3 patients recovered completely without the need for specific therapy.

Management of Overdoses:
Establish and maintain an airway, insure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdose.

Cardiac and vital signs monitoring are recommended along with general symptomatic and supportive measures.

There are no specific antidotes for sertraline.

Due to the large volume of distribution of sertraline, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit.

In managing overdose, the possibility of multiple drug involvement must be considered.

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Dosage

The administration should be initiated at 50 mg daily and increased gradually if needed, noting carefully the clinical response and any evidence of intolerance. It should be kept in mind that there may be a lag in therapeutic response. Increasing the dosage rapidly does not normally shorten this latent period and may increase the incidence of side effects.

Initial Treatment:
As no clear dose-response relationship has been demonstrated, a dose of 50 mg/day is recommended as the initial dose. A gradual increase in dosage may be considered if no clinical improvement is observed. Based on pharmacokinetic parameters, steady-state sertraline plasma levels are achieved after approximately 1 week of once daily dosing; accordingly, dose changes, if necessary, should be made at intervals of at least 1 week. Doses should not exceed a maximum of 200 mg/day.

As with other antidepressants, the full antidepressant effect may be delayed until 4 weeks of treatment or longer.

Sertraline should be administered with food once daily preferably with the evening meal, or, if administration in the morining is desired, with breakfast.

As with many other medications, sertraline should be used with caution in patients with renal and/or hepatic impairment (see Precautions).

Maintenance:
When a satisfactory clinical response has been obtained, the dosage should be reduced (within the 50 to 200 mg range) to the minimum that will maintain relief of symptoms.

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Supplied

50 mg:
Each white and yellow capsule contains: Sertraline HCl 50 mg. Nonmedicinal ingredients: Cornstarch; lactose, anhydrous; magnesium stearate; sodium lauryl sulfate. Capsule shells contain gelatin, silicon dioxide, sodium lauryl sulfate, methyl and propylparabens, titanium dioxide, dye D & C Yellow #10, and dye FD & C Yellow #6. Tartrazine-free. White high density polyethylene botles of 100 and 250.

100 mg:
Each orange capsule contains: Sertraline HCl 100 mg. Nonmedicinal ingredients: Cornstarch; lactose, anhydrous; magnesium stearate; sodium lauryl sulfate. Capsule shells contain gelatin, silicon dioxide, sodium lauryl sulfate, methyl- and propylparabens, titanium dioxide, dye D&C Yellow #10 and dye FD&C Red #40. Tartrazine-free. White high density polyethylene bottles of 100.

Store at controlled room temperature between 15 and 30°C.

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Zoloft

Generic Name: sertraline (SER tra leen)

What is the most important information I should know about Zoloft?

You may have an increased risk of suicidal thoughts or behavior at the start of treatment with an antidepressant medication, especially if you are under 18 years old. Talk with your doctor about this risk. While you are taking Zoloft you will need to be monitored for worsening symptoms of depression and/or suicidal thoughts during the first weeks of treatment, or whenever your dose is changed. In addition to you watching for changes in your own symptoms, your family or other caregivers should be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Contact your doctor promptly if you have any of the following side effects, especially if they are new symptoms or if they get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability, agitation, aggressiveness, severe restlessness, mania (mental and/or physical hyperactivity), thoughts of suicide or hurting yourself. Do not take Zoloft together with pimozide (Orap), or a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate). You must wait at least 14 days after stopping an MAOI before you can take Zoloft. After you stop taking Zoloft, you must wait at least 14 days before you start taking an MAOI. SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Zoloft, do not stop taking the medication without first talking to your doctor.

What is Zoloft?

Zoloft is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs). Zoloft affects chemicals in the brain that may become unbalanced and cause depression, panic, anxiety, or obsessive-compulsive symptoms.

Zoloft is used to treat depression, obsessive-compulsive disorder, panic disorder, anxiety disorders, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD).

Zoloft may also be used for purposes other than those listed in this medication guide.

What should I discuss with my healthcare provider before taking Zoloft?

You may have an increased risk of suicidal thoughts or behavior at the start of treatment with an antidepressant medication, especially if you are under 18 years old. Talk with your doctor about this risk. While you are taking Zoloft you will need to be monitored for worsening symptoms of depression and/or suicidal thoughts during the first weeks of treatment, or whenever your dose is changed. In addition to you watching for changes in your own symptoms, your family or other caregivers should be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks.

Do not use Zoloft if you are using pimozide (Orap), or an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam). Serious and sometimes fatal reactions can occur when these medicines are taken with Zoloft. You must wait at least 14 days after stopping an MAO inhibitor before you can take Zoloft. After you stop taking Zoloft, you must wait at least 14 days before you start taking an MAOI.

Before taking Zoloft, tell your doctor if you have:

• liver or kidney disease;
• seizures or epilepsy;

• bipolar disorder (manic depression); or

• a history of drug abuse or suicidal thoughts.

If you have any of these conditions, you may not be able to use Zoloft, or you may need a dosage adjustment or special tests.

FDA pregnancy category C. SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Zoloft, do not stop taking the medication without first talking to your doctor. It is not known whether Zoloft passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Zoloft?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Your doctor may occasionally change your dose to make sure you get the best results from the medication.

Take each tablet with water.

Zoloft may be taken with or without food.

Try to take the medicine at the same time each day. Follow the directions on your prescription label.

The oral liquid form of this medicine must be diluted before you take it. To be sure you get the correct dose, measure the liquid with medicine dropper provided, not with a regular table spoon. Mix the dose with 4 ounces (one-half cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice. Do not use any other liquids to dilute the medicine. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

It may take 4 weeks or longer before you start feeling better. Do not stop using Zoloft without first talking to your doctor. You may have unpleasant side effects if you stop taking this medication suddenly. Store Zoloft at room temperature away from moisture and heat.

What happens if I miss a dose of Zoloft?

Take the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take extra medicine to make up the missed dose.

What happens if I overdose with Zoloft?

Seek emergency medical attention if you think you have taken too much of this medication. Symptoms of a Zoloft overdose may include dizziness, drowsiness, nausea, vomiting, rapid heartbeat, agitation, tremor, confusion, seizures, and coma.

What should I avoid while taking Zoloft?

Avoid drinking alcohol, which can increase some of the side effects of Zoloft.

Do not take the liquid form of Zoloft if you are taking disulfiram (Antabuse). Liquid Zoloft may contain alcohol and you could have a severe reaction to the disulfiram.

Avoid using other medicines that make you sleepy (such as cold medicine, pain medication, muscle relaxers, medicine for seizures, other medication for depression or anxiety). They can add to sleepiness caused by Zoloft.

Zoloft can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

What are the possible side effects of Zoloft?

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Contact your doctor promptly if you have any of the following side effects, especially if they are new symptoms or if they get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability, agitation, aggressiveness, severe restlessness, mania (mental and/or physical hyperactivity), thoughts of suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

• seizure (convulsions);

• tremors, shivering, muscle stiffness or twitching;

• problems with balance or coordination; or

• agitation, confusion, sweating, fast heartbeat.

Other less serious side effects are more likely to occur, such as:

• feeling nervous, restless, or unable to sit still;

• drowsiness, dizziness, weakness;

• sleep problems (insomnia);

• nausea, diarrhea, dry mouth, or changes in appetite or weight; or

• decreased sex drive, impotence, or difficulty having an orgasm.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Zoloft?

Talk to your doctor before taking any medicine for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin, piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others. Taking any of these drugs with Zoloft may cause you to bruise or bleed easily.

Before taking Zoloft, tell your doctor if you are using any of the following medicines:

• tramadol (Ultram, Ultram ER, Ultracet);

• digitoxin (Crystodigin);

• phenytoin (Dilantin), valproate (Depacon, Depakene);

• lithium (Lithobid, Eskalith);

• a blood thinner such as warfarin (Coumadin);

• any other antidepressants such as amitriptyline (Elavil), citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Pamelor), or paroxetine (Paxil);

• almotriptan (Axert), frovatriptan (Frova), sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt), or zolmitriptan (Zomig); or

• heart rhythm medication such as flecainide (Tambocor), propafenone (Rhythmol), and others.

If you are using any of these drugs, you may not be able to use Zoloft, or you may need dosage adjustments or special tests during treatment.

There may be other drugs not listed that can affect Zoloft. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information on Zoloft?

• Your pharmacist has additional information about Zoloft written for health professionals that you may read.

What does my medication look like?

Sertraline is available with a prescription under the brand name Zoloft. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

• Zoloft 25 mg-capsule-shaped, green, film-coated, scored tablets

• Zoloft 50 mg--capsule-shaped, light-blue, film-coated, scored tablets

• Zoloft 100 mg--capsule-shaped, light-yellow, film-coated, scored tablets

• Zoloft Oral Concentrate 20 mg/mL-clear, colorless solution with a menthol scent

Sertraline

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Sertraline
Systematic (IUPAC) name
(1S)-cis-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro- N-methyl-1-naphthalenamine
Identifiers
CAS number	79617-96-2
ATC code	N06AB06
PubChem	68617
DrugBank	APRD00175
Chemical data
Formula	C17H17NCl2
Mol. weight	306.229 g/mol
Pharmacokinetic data
Bioavailability	44%
Metabolism	N-demethylation (liver)
Half life	~26 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral

"Lustral" redirects here. For the electronic music band, see Lustral (band).

Sertraline hydrochloride (also labeled under numerous brand names: Zoloft, Sertralin, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton, Xydep, Serlain, Concorz) is a popular orally administered antidepressant of the selective serotonin reuptake inhibitor (SSRI) type. It was first approved by the Food and Drug Administration (FDA) in 1991.

Contents [hide] 1 Invention 2 Indications 2.1 Approved 2.2 Unapproved, off-label, and investigational 3 Side effects 4 Distribution 5 Formulations 6 Green technology 7 Precautions 8 Dopamine 9 Controversy 10 Discontinuation Syndrome 11 Popular culture 12 References 13 External links

[edit] Invention

The invention of Sertraline has been attributed to two scientists at Pfizer: Steve Werner and Billy Dzomba. At the time, the notion that the neurotransmitter serotonin and depression might be linked was a fairly new concept. Together, Werner and Dzomba explored a variety of potential anti-depressant compounds and, within the space of one year, developed Sertraline.^[1]

 

[edit] Indications

 

[edit] Approved

Sertraline is used medically mainly to treat the symptoms of depression and anxiety. It is also prescribed for the treatment of obsessive-compulsive disorder (OCD),^[2] post-traumatic stress disorder (PTSD),^[3] premenstrual dysphoric disorder (PMDD),^[4] panic disorder (PD)^[5] and social phobia/social anxiety disorder.^[6]

 

[edit] Unapproved, off-label, and investigational

Sertraline can also be used in the treatment of general anxiety disorder,^[7] binge eating disorder,^[8] and premature ejaculation.^[9]

There is also evidence that sertraline may be effective in the treatment of refractory neurocardiogenic syncope in children and adolescents.^[10]

A study has shown that sertraline is an effective treatment for impulsive aggressive behavior in personality disordered patients.^[11]

 

[edit] Side effects

Sertraline can have adverse effects, including: sleep disorder (both insomnia and increased sleep time), asthenia, gastrointestinal complaints, tremors, weight gain, confusion, dizziness, anorgasmia, nausea/vomiting, bruxism, mild depersonalization, and decreased libido. Sertraline, like all of the other SSRI drugs, can increase anxiety and depression symptoms in the first few days/week of use. These side effects generally go away as the body adjusts chemicals to adjust to the drug. Sertraline can induce mania or hypomania in around 0.5% of patients. It has also been known to cause minor weight loss. It is contraindicated in individuals taking monoamine oxidase inhibitors (MAOIs) or undergoing electroconvulsive therapy. Patients are advised to stop taking MAOIs for at least 14 days before beginning a course of sertraline.^[12]

Until 2003, sertraline was only approved for use in adults ages 18 and over; that year it was approved by the FDA for use in treating children ages 6 to 17 with extreme obsessive compulsive disorder. In June 2004, Britain banned Zoloft's use by minors and in February 2005, Pfizer was forced to change Zoloft's labeling to include information regarding increased incidences of suicidal behavior and depression in adolescent users of the drug. According to mentalhealth.com, Zoloft is not currently recommended or advised for use in individuals under the age of 18. After these changes, multiple incidences and at least one medical study showed an increased suicide risk in seniors who were taking Zoloft. In response to these findings, the FDA released a public health warning. This warning indicates that anyone currently using Zoloft for any reason has a greater chance of exhibiting suicidal thoughts or behaviors regardless of age. This warning is questionable, however, due to the types of illnesses Zoloft is used to treat, it is impossible to determine if these tendencies are a side effect of the drug or the illness the drug is meant to treat.

Zoloft has long been seen as the best option for breastfeeding mothers who wish to continue breastfeeding and be able to take their antidepressants. Despite its apparent safety and effectiveness during the breastfeeding period, recent studies and consumer complaints have seen a need to alter Zoloft's labeling regarding use during the third trimester of pregnancy. Though there are no teratogenic effects associated with Zoloft, there is reason to be concerned about its effects on infants who were exposed to sertraline during the third trimester in utero. It seems that Zoloft use in late pregnancy significantly increases the potential need for hospitalization and breathing assistance in the newborn period and has also been shown to cause an increased risk of neonatal death. In light of this increased risk it is still being used due to the greater potential risk of a seriously depressed mother to herself and her fetus. Like all other medications, Zoloft's use must be decided only after carefully weighing out all potential risks and benefits.

Although SSRI anti-depressants may cause problems in newborn babies whose mothers took Zoloft during pregnancy, the ceasing of Zoloft consumption during pregnancy may cause a relapse of depression. If you are planning on becoming pregnant, or are currently pregnant and are taking Zoloft, do not stop taking this medication. Consult your physician first.^[13]

According to the manufacturer's website, "if depression is left untreated, the risk of childhood suicide increases about 12 times, according to federal figures".^[14]

Sertraline and other SSRIs have been shown to cause sexual side effects in up to 98% of both males and females taking them.^[15] Sometimes, the sexual side effects last months, years, or permanently after the drug has been withdrawn. This disorder is known as Post SSRI Sexual Dysfunction.

 

[edit] Distribution

This drug has been heavily prescribed in the United States. According to one source, more than 115 million prescriptions for Sertraline had been written in the U.S. by February 2000.^[16] The world over, $3.5 billion worth of Zoloft was sold in 2005.^[17]

 

[edit] Formulations

Zoloft logo

Sertraline is manufactured by Pfizer and sold as Zoloft in the United States as small green 25 mg tablets, blue 50 mg tablets, and yellow 100 mg tablets (Generic 100 mg sertraline tablets are also yellow), each of which is scored to allow easy halving.

In the UK, the brand name is Lustral and is available in white 50 mg or 100 mg scored tablets, according to the British National Formulary (BNF). Elsewhere in the EU the brand name is Zoloft, available in white 50 mg or 100 mg scored tablets. In Australia, only the 50 mg and 100 mg strengths are available, both as white tablets.

Sertraline is an odorless, white, sparingly soluble crystalline solid. The minimum effective dose is usually 50 mg per day (it can be still effective at 25 mg or 37.5 mg), but lower doses may be used in the initial weeks of treatment to acclimate the patient's body, especially the liver, to the drug and to minimize the severity of any side effects. Patients who do not experience relief of symptoms at 50 mg a day may have their dose increased, up to 200 mg a day.

Drug maker Pfizer Inc. confirmed that its subsidiary Greenstone Ltd. is prepared to release a generic version of the antidepressant Zoloft to compete with generic drug makers, who can release their own versions after the drug's patent expires.

The patent for this brand-name drug expired in June 2006.^[18] The drug is now available in generic form in the United States. The generic version of the drug is being produced by Greenstone Ltd.(a Pfizer Inc. subsidiary) and Israeli drug maker Teva Pharmaceutical Industries Ltd.^[19] In Scandinavia a generic drug called Sertralin, manufactured by HEXAL, is available. The price differences between Zoloft and Sertraline are as much as 1.50 dollars per pill.^{[citation needed]} In India, this drug is sold under the name Zosert.

 

[edit] Green technology

In 2002, Pfizer, inc. received an award from the U.S. Environmental Protection Agency, specifically in relation to the manufacture of sertraline. According to the EPA, Pfizer introduced methods of production that reduced necessary inputs of raw materials and allowed for a reduction of toxic waste. These new methods have been described as more energy-efficient, permitting the company to multiply sertraline production two-fold. Further, the application of this new process is purportedly safer for workers.^[20]

 

[edit] Precautions

• Liver impairment can affect the elimination of this drug from the body. If someone with liver impairment is treated with sertraline, lower or less frequent dosage should be used.

• Patients should limit their alcohol intake while on sertraline (or any antidepressant). Because the liver is doubly taxed with processing both substances (in addition to any other drugs the patient may be taking), alcohol remains in the bloodstream longer, so the effects of alcohol may be more strongly and quickly felt by people taking sertraline or other antidepressants. Heavy alcohol consumpution while on any SSRI can damage liver cells much quicker than those off of the drugs.

• According to some studies grapefruit juice might interfere with the metabolisation of sertraline, increasing its concentration in the blood.

• People 80 years or older should be started on 25 mg initial dose.

 

[edit] Dopamine

Sertraline appears to also be a minor dopamine reuptake inhibitor (see Dopamine reuptake inhibitor). Dopamine is responsible for the 'feel good' feeling in the brain. While this generally will leave the user of the drug feeling great, it is not the intent of the drug. Interestingly, since activities like smoking cigarettes increases dopamine levels in the brain, some smokers actually have increased cravings while on SSRI drugs. There are numerous studies on this. [1]

 

[edit] Controversy

In June 2003, Britain banned sertraline's use for patients under 18 years of age after studies showed a link to increasing suicidal rates. Similar concern has prevailed in the United States, where only the anti-depressant fluoxetine (another SSRI) was officially banned by the FDA for the treatment of depression in minors. However, because the antidepressant-suicide link is correlational, scientists do not know whether the increased suicide risk for people taking antidepressants occurs because the drugs make people suicidal, whether suicide occurs because the drugs un-depress the people enough to motivate the energy required to commit suicide (a popular theory), whether people statistically more likely to commit suicide are over-represented among takers of Zoloft, or because of a fourth, unknown factor.

The brand-name form of setraline, Zoloft, was widely advertised to consumers as "correcting a chemical imbalance", a claim not found in the FDA-approved product labeling. Hundreds of millions of dollars were spent promoting Zoloft this way while it was still on-patent. Some have argued that this advertising may lead consumers to believe that they must take Zoloft to recover when in fact they may benefit from other non-medical treatments such as psychotherapy or exercise.^[21][22]

In the case of Hawkins v The Commonwealth (an Australian court case from the state of New South Wales), Zoloft was described as an important factor in Hawkins murder (through strangling) of his wife. Hawkins had been depressed, was prescribed 50 mg of Zoloft a day and on his first day of treatment took 250 mgs. He claimed on the night of the murder that he couldn't sleep, was agitated and claimed he had hallucinations during the attack on his wife. As a result of this case Zoloft received a large amount of negative publicity, with questions being raised about its impact on behaviour. ^[23]

 

[edit] Discontinuation Syndrome

Main article: SSRI discontinuation syndrome

Zoloft, along with other SSRIs, has been associated with a "cessation syndrome." This syndrome has both somatic and psychological elements, although SSRIs fall short of being classified as addictive. This non-addictive classification stems from the fact persons given the drug will not seek it out in ever-increasing quantities. Although Zoloft is defined as non-habit forming, the existence of SSRI discontinuation syndrome often necessitates a gradual tapering of one's prescribed dose when seeking to stop SSRI therapy. The prescription insert for Zoloft describes the potential side effects SSRI discontinuation as follows:

"During marketing of Zoloft and other SSRIs and SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g. paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms."^[24]