Zoloft
Brand name: Zoloft
DESCRIPTION Zoloft
Uses Zoloft
Zoloft is safe and effective for the treatment of depression and anxiety.
Why? It's the #1 doctor-prescribed brand of its kind. Zoloft has treated millions
of people with more types of depression and anxiety than any brand of its
kind for over 12 years. And Zoloft is available in multiple strengths, so
your doctor can decide the right dose for you.
Drug monograph "Zoloft"
Summary Zoloft
Zoloft 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 Zoloft:
Not to be use with an MAOI or within 14 days of starting or discontinuing MAOI
therapy. Concomitant use with pimozide.
Precautions Zoloft:
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 Zoloft:
Nausea, diarrhea/loose stools, dyspepsia, male sexual dysfunction (primarily
ejaculatory delay), insomnia, somnolence, tremor, increased sweating, dry mouth,
dizziness.
Interactions Zoloft:
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 Zoloft:
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 Zoloft:
25 mg, 50 mg, 100mg capsules.
Pharmacology Zoloft
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 Zoloft:
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 Zoloft:
The pharmacokinetics of sertraline in patients with significant hepatic
or renal dysfunction have not been determined.
Indications Zoloft
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.
Contraindications Zoloft
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.
Contraindications Zoloft
None.
Contraindications Zoloft
Activation of Mania/Hypomania Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
General Zoloft:
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 Zoloft:
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.
Hepatic Dysfunction Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
The effect of sertraline on labor and delivery in humans is unknown.
Children Zoloft:
The safety and effectiveness of sertraline in children below the age of 18 have not been established.
Geriatrics Zoloft:
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 Zoloft:
Co-Administration of Drugs Highly Bound to Plasma Proteins Zoloft:
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 Zoloft:
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 Zoloft:
There are no clinical studies with the combined use of electroconvulsive
therapy (ECT) and sertraline.
Alcohol Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
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.
Adverse Effects Zoloft
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.
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 Zoloft:
Infrequent: Flushing, mydriasis, increased saliva, cold clammy skin. Rare: Pallor.
Cardiovascular Zoloft:
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 Zoloft:
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 Zoloft:
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 Zoloft:
Rare: Exophthalmos, gynecomastia.
Gastrointestinal Disorders Zoloft:
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 Zoloft:
Frequent: Asthenia. Infrequent: Malaise, generalized edema, rigors,
weight decrease, weight increase. Rare: Enlarged abdomen, halitosis,
otitis media, aphthous stomatitis.
Hematopoietic and Lymphatic Zoloft:
Infrequent: Lymphadenopathy, purpura. Rare: Anemia, anterior chamber eye hemorrhage.
Metabolic and Nutritional Disorders Zoloft:
Rare: Dehydration, hypercholesterolemia, hypoglycemia.
Musculo-Skeletal System Disorders Zoloft:
Infrequent: Arthralgia, arthrosis, dystonia, muscle cramps, muscle weakness. Rare: Hernia.
Psychiatric Disorders Zoloft:
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 Zoloft:
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 Zoloft:
Infrequent: Bronchospasm, coughing, dyspnea, epistaxis. Rare: Bradypnea,
hyperventilation, sinusitis, stridor.
Special Senses Zoloft:
Infrequent: Abnormal accommodation, conjunctivitis, diplopia, earache, eye pain,
xerophthalmia. Rare: Abnormal lacrimation, photophobia, visual field defect.
Urinary System Disorders Zoloft:
Infrequent: Dysuria, face edema, nocturia, polyuria, urinary incontinence.
Rare: Oliguria, renal pain, urinary retention.
Laboratory Tests Zoloft:
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.
Overdose Zoloft
Symptoms and Treatment Zoloft:
Human Experience Zoloft:
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 Zoloft:
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.
Dosage Zoloft
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 Zoloft:
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 Zoloft:
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.
Supplied Zoloft
50 mg Zoloft:
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 Zoloft:
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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