Buy Zoloft at CanPharm

The mechanism of action 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 (alpha1, alpha2 & beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, 5-HT2) or benzodiazepine binding sites.

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

Zoloft Pharmacokinetics

Following multiple oral once-daily doses of 200 mg, the mean peak plasma concentration (Cmax) of sertraline is 0.19 µg/mL occurring between 6 to 8 hours post-dose. The area under the plasma concentration time curve is 2.8 mg·hr/L. For desmethylsertraline, Cmax is 0.14 μg/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 ZOLOFT 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.

Analyses for gender effects on outcome did not suggest any differential responsiveness on the basis of sex.

Liver and Renal Disease: The pharmacokinetics of sertraline in patients with significant hepatic or renal dysfunction have been determined (see Precautions and Dosage).

Panic Disorder: Four placebo-controlled clinical trials have been performed to investigate the efficacy of ZOLOFT in panic disorder: two flexible dose studies and two fixed dose studies. At the last week of treatment (week 10 or 12), both flexible dose studies and one of the fixed dose studies showed statistically significant differences from placebo in favour of ZOLOFT in terms of mean change from baseline in the total number of full panic attacks (last observation carried forward analysis). As the flexible dose studies were of identical protocol, data for these investigations can be pooled. The mean number of full panic attacks at baseline was 6.2/week (N=167) in the ZOLOFT group and 5.4/week in the placebo group (N=175). At week 10 (last observation carried forward analysis), the mean changes from baseline were −4.9/week and −2.5/week for the ZOLOFT and placebo groups, respectively. The proportion of patients having no panic attacks at the final evaluation was 57% in the placebo group and 69% in the ZOLOFT group. The mean daily dose administered at the last week of treatment was approximately 120 mg (range: 25-200 mg) in the flexible dose studies. No clear dose-dependency has been demonstrated over the 50 to 200 mg/day dose range investigated in the fixed dose studies.

Obsessive-Compulsive Disorder: Five placebo-controlled clinical trials, in adults, of 8 to 16 weeks in duration have been performed to investigate the efficacy of ZOLOFT in obsessive-compulsive disorder: four flexible dose studies (50-200 mg/day) and one fixed dose study (50, 100, & 200 mg/day). Results for three of the four flexible dose studies and the 50 and 200 mg dose groups of the fixed dose study were supportive of differences from placebo in favour of ZOLOFT in terms of mean change from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale and/or the National Institute of Mental Health Obsessive-Compulsive Scale (last observation carried forward analysis). No clear dose-dependency was demonstrated over the 50 to 200 mg/day dose range investigated in the fixed dose studies. In the flexible dose studies, the mean daily dose administered at the last week of treatment ranged from 124-180 mg.

One placebo-controlled clinical trial of 12 weeks duration, was performed in children and adolescents aged 6-17 years, to investigate the efficacy of ZOLOFT in obsessive-compulsive disorder. The study used flexible dosing, starting with 25 mg/day in children 6-12 years old (ZOLOFT n=53, placebo n=54) and with 50 mg/day in adolescents 13-17 years old (ZOLOFT n=39, placebo n=41). In both age groups, ZOLOFT was titrated up to a maximum 200 mg/day, over 4 weeks, as tolerated. The mean dose for completers (74/92 ZOLOFT treated patients) was 178 mg/day. Results showed statistically significant differences from placebo in favour of ZOLOFT in terms of mean change from baseline to endpoint (last observation carried forward analysis) on the Children's Yale-Brown Obsessive Compulsive Scale (p=0.005), the National Institute of Mental Health Obsessive-Compulsive Scale (p=0.019) and the Clinical Global Impresssion Improvement Rating Scale (p=0.002).

The long term safety, including effects on growth and development, in patients under 18 years of age, has not been established.

ZOLOFT (sertraline hydrochloride) is indicated for the symptomatic relief of depressive illness. However, the antidepressant action of ZOLOFT 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 ZOLOFT has indicated that ZOLOFT 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.

ZOLOFT is indicated for the symptomatic relief of panic disorder, with or without agoraphobia. The efficacy of ZOLOFT was established in 10-week and 12-week controlled trials of patients with panic disorder as defined according to DSM-III-R criteria.

The effectiveness of ZOLOFT in long-term use for the symptomatic relief of panic disorder (i.e., for more than 12 weeks) has not been systematically evaluated in placebo-controlled trials. Therefore, the physician who elects to use ZOLOFT for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

ZOLOFT is indicated for the symptomatic relief of obsessive-compulsive disorder (OCD). The obsessions or compulsions must be experienced as intrusive, markedly distressing, time-consuming, or significantly interfering with the person's social or occupational functioning.

The effectiveness of ZOLOFT in long-term use for the symptomatic relief of OCD ( i.e., for more than 12 weeks) has not been systematically evaluated in placebo-controlled trials. Therefore, the physician who elects to use ZOLOFT for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

ZOLOFT (sertraline hydrochloride) is contraindicated in patients with known hypersensitivity to the drug.

Cases of serious, sometimes fatal, reactions have been reported in patients receiving ZOLOFT (sertraline hydrochloride) in combination with a monoamine oxidase inhibitor (MAOI), including the selective MAOI, selegiline and the reversible MAOI (reversible inhibitor of monoamine oxidase-RIMA), moclobemide. Some cases presented with features resembling the serotonin syndrome. Similar cases, have been reported with other antidepressants during combined treatment with an MAOI and in patients who have recently discontinued an antidepressant and have been started on an MAOI. Symptoms of a drug interaction between an SSRI and an MAOI 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, ZOLOFT should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should elapse after discontinuing ZOLOFT treatment before starting an MAOI.

The concomitant use of ZOLOFT and pimozide is contraindicated as ZOLOFT has been shown to increase plasma pimozide levels. Elevation of pimozide blood concentration may result in QT interval prolongation and severe arrhythmias including torsades de pointes (see Precautions and Information for the Patient).

• Recent analyses of placebo-controlled clinical trial safety databases from SSRI and other newer antidepressants suggest that use of these drugs in patients under the age of 18 may be associated with behavioral and emotional changes, including an increased risk of suicidal ideation and behavior over that of placebo.

  
  

• The small denominators in the clinical trial database, as well as the variability in placebo rates, preclude reliable conclusions on the relative safety profiles among these drugs.

  
  

• There are clinical trial and post-marketing reports with SSRIs and other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type adverse events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization. In some cases, the events occurred within several weeks of starting treatment.

  
  

Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behavior is advised in patients of all ages. This include monitoring for agitation-type emotional and behavioral changes.

Patients currently taking ZOLOFT should not be discontinued abruptly, due to risk of discontinuation symptoms. At the time that a medical decision is made to discontinue an SSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abrupt cessation is recommended.

See Contraindications.

During clinical testing in depressed patients, hypomania or mania occurred in approximately 0.6% of ZOLOFT (sertraline hydrochloride) 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.

ZOLOFT has not been evaluated in patients with seizure disorders. These patients were excluded from clinical studies during the product's premarket testing. No seizures were observed among approximately 3000 patients treated with ZOLOFT in the development program for depression. However, 4 patients out of approximately 1800 (220 <18 years of age) exposed during the development program for obsessive-compulsive disorder experienced seizures representing a crude incidence of 0.2%. Three of these patients were adolescents, two with a seizure disorder and one with a family history of seizure disorder, none of whom were receiving anticonvulsant medication. Accordingly, ZOLOFT should be introduced with care in patients with a seizure disorder.

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. It should be noted that a causal role for SSRIs and other antidepressants in inducing self-harm or harm to others has not been established. In order to minimize the opportunity for overdosage, prescriptions for ZOLOFT should be written for the smallest quantity of drug consistent with good patient management (see Warnings, Potential Association with Behavioral and Emotional Changes, Including Self-harm ).

Because of the well-established co-morbidity between both obsessive-compulsive disorder and depression and panic disorder and depression, the same precautions should be observed when treating patients with obsessive-compulsive disorder and panic disorder.

When discontinuing treatment, patients should be monitored for symptoms which may be associated with discontinuation (e.g. dizziness, abnormal dreams, sensory disturbances (including paresthesias and electric shock sensations), agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting and sweating or other symptoms which may be of clinical significance (see Adverse Effects). A gradual reduction in the dosage over several weeks, rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient's clinical response (see Adverse Effects and Dosage).

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.

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

ZOLOFT has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. However, the electrocardiograms of 1006 patients who received ZOLOFT in double-blind trials were evaluated and the data indicate that ZOLOFT is not associated with the development of clinically significant ECG abnormalities.

In placebo-controlled trials, the frequency of clinically noticeable changes (±15-20 mmHg) in blood pressure was similar in patients treated with either ZOLOFT or placebo.

Sertraline is extensively metabolized by the liver. A single dose pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a prolonged elimination half-life and increased AUC in comparison to normal subjects. The use of sertraline in patients with hepatic disease must be approached with caution. If sertraline is administered to patients with hepatic impairment, a lower or less frequent dose should be considered (see Pharmacology and Dosage).

ZOLOFT is extensively metabolized and excretion of unchanged drug in the urine is a minor route of elimination. In 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.

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.

The safety of ZOLOFT 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.

Post-marketing reports indicate that some neonates exposed to ZOLOFT, SSRIs (Selective Serotonin Reupt