You should also Talk with doctor about any uncertainites,or worries you have like the above stated. I hope this helps
ZOLOFT TABLETS 50 mg
(and dosage form)
ZOLOFT TABLETS 50 mg
Sertraline hydrochloride is a naphthylamine derivative, having the following chemical name: (1S,cis)-4-(3,4-dichlorophenyl)-1,2,3,4-... hydrochloride. Sertraline hydrochloride is a white crystalline powder that is slightly soluble in water and isopropyl alcohol, and sparingly soluble in ethanol. It has a molecular weight of 342.7.
Each ZOLOFT TABLET 50 mg contains sertraline hydrochloride equivalent to 50 mg sertraline.
ZOLOFT TABLETS 50 mg include the following inert ingredients: calcium hydrogen phosphate, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycollate, magnesium stearate, hydroxypropyl methyl cellulose, polyethylene glycol, polysorbates and titanium dioxide.
A 1.2 Psychoanaleptics (Antidepressants)
The mechanism of action of sertraline is presumed to be linked to the inhibition of central nervous system neuronal uptake of serotonin (5HT). Studies at clinically relevant doses in man have shown that sertraline blocks the uptake of serotonin into human platelets. Sertraline has been shown to be a specific inhibitor of neuronal serotonin re-uptake in vitro and has only very weak effects on the norepinephrine and dopamine neuronal re-uptake.
It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals. In vitro studies have shown that sertraline does not enhance catecholaminergic activity and it has no affinity for cholinergic, serotonergic (5HT1A, 5HT1B, 5HT2), dopaminergic, adrenergic (alpha1, alpha2, beta) histaminergic, GABA or benzodiazepine receptors. The chronic administration of sertraline in animals was associated with downregulation of brain norepinephrine receptors as observed with other clinically effective antidepressants.
In a single-dose study, sertraline exhibited dose proportional pharmacokinetics over the range 50 mg-200 mg. After oral administration over the range of 50 to 200 mg once daily for 14 days, mean peak blood levels were reached at 4,5-8,4 hours post dose. The average terminal plasma half-life is about 26 hours. Steady-state plasma levels are reached after approximately one week of once daily dosing. Approximately 98% of the circulating drug is bound to plasma proteins. Consistent with the terminal elimination half-life, there is approximately two-fold accumulation with repeated dosing as compared to a single dose.
Sertraline undergoes extensive first pass hepatic metabolism. Both in vitro biochemical and in vivo pharmacological testing have shown the principal metabolite, N-desmethylsertraline, to have significantly less clinical activity. Both sertraline and N-desmethylsertraline are extensively metabolised with only a small amount (<0,2%) of unchanged sertraline excreted in the urine. About 40-45% of the dose administered radioactively was recovered in the urine and a similar amount in the faeces, including 12-14% unchanged sertraline. The terminal elimination half-life of N-desmethylsertraline is approximately 62 to 104 hours. Desmethylsertraline exhibits time related dose dependent increases in AUC, Cmax and Cmin with a 5 to 9 fold increase in their parameters between day 1 and day 14.
Protein binding - In vitro protein binding studies performed with radiolabeled ³H-sertraline showed that sertraline is highly bound to serum proteins (98%) in the range of 20 to 500 ng/mL.
Age - Sertraline plasma clearance in a group of 16 (8 male, 8 female) elderly patients treated for 14 days at a dose of 100 mg/day was approximately 40% lower than in a similarly studied group of younger (25 to 32 year old) individuals. Steady state, therefore, should be achieved after 2 to 3 weeks in older patients. The same study showed a decreased clearance of desmethylsertraline in older males, but not in older females.
Liver disease - The administration of sertraline is delayed in patients with impaired liver function. Dosages should be reduced. (See Warnings)
ZOLOFT is indicated for the treatment of major depressive disorders such as single episodes and recurrent depression.
ZOLOFT is also indicated for the treatment of obsessive compulsive disorder (OCD).
ZOLOFT is also indicated for the treatment of panic disorder, with or without agoraphobia.
Panic disorder is characterised by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and /or a significant change in behaviour related to the attacks.
The efficacy of Zoloft was established in three 10-12 week trials in panic disorder patients.
Panic disorder is characterised by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart, or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, light-headed, or faint; (9) derealisation (feelings of unreality) or depersonalisation (being detached from oneself); (10) fear of loosing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes.
The effectiveness of Zoloft (sertraline hydrochloride) in long-term use, that is, for more than 12 weeks, has not been systematically evaluated in controlled trials. Therefore the physician who elects to use Zoloft for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see Dosage and Directions for Use)
Zoloft is contra-indicated in patients with known hypersensitivity to sertraline.
The concomitant use of Zoloft with a monoamine oxidase inhibitor (MAOI) is contra-indicated -see “Warnings”.
Use in hepatic or renal insufficiency - see “Warnings - Use in patients with concomitant illness”.
Use in pregnancy - There have been no adequate and well-controlled studies in pregnant women. Zoloft should be used in pregnancy only if the perceived benefits outweigh the risks. Women of child-bearing potential should employ an adequate method of contraception if taking Zoloft.
Use during lactation - Limited data concerning sertraline levels in breast milk are available. Isolated studies in very small numbers of nursing mothers and their infants indicated negligible or undetectable levels of sertraline in infant serum, although levels in breast milk were more concentrated than in maternal serum. Use in nursing mothers is not recommended unless, in the judgement of the physician, the benefit outweighs the risk.
Activation of mania/hypomania - During premarketing testing, hypomania or mania occurred in approximately 0.4% 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 and antiobsessional agents.
Weight loss - Significant weight loss may be an undesirable result of treatment with sertraline for some patients, but on average, patients in controlled trials had minimal, 0.5 kg-1.0 kg weight loss, versus smaller changes on placebo. Only rarely have sertraline patients been discontinued for weight loss.
Seizure- Seizures have been observed occasionally in patients using Zoloft. Zoloft should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Zoloft should be discontinued in any patient who develops seizures.
Suicide - The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high risk patients should accompany initial drug therapy. Prescriptions for Zoloft should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Weak uricosuric effect - Zoloft is associated with a mean decrease in serum uric acid of approximately 7%. The clinical significance of this weak uricosuric effect is unknown, and there have been no reports of acute renal failure with Zoloft.
Electroconvulsive therapy - There are no clinical studies establishing the risks or benefits of combined use of ECT and Zoloft.
Driving/Use of machinery - Clinical pharmacology studies have shown that Zoloft has no effect on psychomotor performance. However patients should be cautioned accordingly when driving a car or operating machinery.
Use in patients with concomitant illness - Clinical experience with Zoloft in patients with certain concomitant systemic illness 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. Patients with these diagnoses were excluded from clinical studies during the product's premarket testing. However, the electrocardiograms of 774 patients who received Zoloft in double-blind trials were evaluated and the data indicate that Zoloft is not associated with the development of significant ECG abnormalities.
Liver impairment - As might be predicted from its primary site of metabolism, liver impairment can affect the elimination of sertraline. The elimination half-life of sertraline was prolonged in a multiplestudy of patients with mild, stable cirrhosis, with a mean of 52 hours compared to 22 hours seen in subjects without liver disease. The AUC and the C max were shown to be approximately three fold greater in comparison to normal subjects. There were no significant differences in plasma protein binding observed between the two groups. This suggests that the use of sertraline in patients with liver disease must be approached with caution. If Zoloft is administered to patients with liver disease, a lower or less frequent dose should be considered.
Renal impairment - In patients with mild to moderate renal impairment (creatinine clearance 20-60 mL/min) or severe renal impairment (creatinine clearance <30 mL/min), multiple dose pharmacokinetic parameters (AUC or C max) were modest but significantly different compared with controls. Zoloft should be used with care in these patients. The dose of Zoloft may have to be reduced in patients with impaired renal function.
Monoamine oxidase inhibitors - Cases of serious reactions, sometimes fatal, have been reported in patients receiving Zoloft in combination with a MAOI, including the selective MAOI, selegiline, and the reversible MAOI, moclobemide. Some cases presented with features resembling neuroleptic malignant syndrome. Similar cases, sometimes fatal, have been reported with other antidepressants during combined treatment with a MAOI and in patients who have recently discontinued an antidepressant or antiobsessional drug and have been started on a MAOI. Symptoms of a drug interaction between a SSRI and a 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 a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should elapse after discontinuing sertraline treatment and starting a MAOI.
CNS depressants and alcohol - Co-administration of Zoloft (sertraline 200 mg daily) did not potentiate the effects of alcohol, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects. However the concomitant use of Zoloft and alcohol in depressed patients is not recommended.
Interference with cognitive and motor performance - In controlled studies, Zoloft did not cause sedation and did not interfere with psychomotor performance.
DOSAGE AND DIRECTIONS FOR USE
ZOLOFT TABLETS should be given as a single daily dose with or without food.
The starting dose is 50 mg daily and the usual therapeutic dose in depression is 50 mg daily. In difficult to treat patients, the dose may be titrated up in 50 mg increments at 2 weekly intervals, to 150 mg-200 mg.
The minimum effective dose in OCD is also 50 mg daily and increases above 100 mg daily did not have any additional benefit. Full activity is usually seen after 2-4 weeks and even longer in OCD. Effect may however be seen within 7 days.
For panic disorder, the minimum recommended effective dose of sertraline is 50 mg/day. However, therapy for panic disorder should commence at 25 mg/day, increasing to 50 mg/day after one week. This dosage regimen has been demonstrated to reduce the frequency of early treatment emergent side effects characteristic of panic disorder.
Use in the elderly - No special precautions are required. The usual adult dosage is recommended.
Use in children - The use of Zoloft in children is not recommended as safety and efficacy have not been established.
Use in hepatic and renal impairment - see “Warnings - Use in patients with concomitant illness”
SIDE EFFECTS AND SPECIAL PRECAUTIONS
The most commonly observed adverse events associated with the use of Zoloft (sertraline hydrochloride) and not seen at an equivalent incidence among placebo treated patients were: gastrointestinal complaints, including anorexia, nausea, diarrhoea/loose stools and dyspepsia; tremor; dizziness; insomnia; somnolence; increased sweating; dry mouth; and sexual dysfunction (primarily ejaculatory delay in males).
The following adverse events were also observed in equal or greater numbers than placebo in patients who participated in placebo-controlled clinical trials:
Central and peripheral nervous system symptoms: Headache, paresthesia, hypoesthesia, twitching, hypertonia
Disorders of skin and appendages: Rash
Gastro-Intestinal symptoms: Constipation, vomiting, flatulence, anorexia, abdominal pain, appetite increased
General: Fatigue, hot flushes, fever, back pain
Metabolic and nutritional symptoms: Thirst
Musculo-skeletal system symptoms: Myalgia
Psychiatric symptoms: Agitation, nervousness, anxiety, yawning, female sexual dysfunction, impaired concentration, and psychosis.
Reproductive: Menstrual Symptoms
Respiratory system symptoms: Rhinitis, pharyngitis
Special senses: Vision abnormal, tinnitus, taste perversion,
Urinary system symptoms: Micturition frequency, micturition disorder
There have been reports of extrapyramidal symptoms associated with the use of Zoloft and of aggravation of Parkinson's disease in patients taking Zoloft. Caution should be exercised when prescribing Zoloft to patients with extrapyramidal disorders and patients should be carefully monitored.
Abrupt discontinuation of Zoloft may lead to withdrawal symptoms which include dizziness, sweating, nausea, insomnia, tremor, confusion, sensory disturbances, agitation and anxiety.
Other side effects include: movement disorders (such as gait abnormalities), convulsions, hyperprolactinemia, galactorrhoea and rarely, erythema multiforme, pancreatitis and serious liver events (including hepatitis, jaundice and liver failure). The following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: paresthesia, hypoesthesia, depressive symptoms, hallucinations, aggressive reaction, agitation, anxiety and psychosis.
The side effect profile commonly observed in double–blind, placebo controlled studies in patients with Panic Disorder was similar to that observed in clinical trials in patients with depression.
Asymptomatic elevations of serum transaminases (SGOT and SGPT) have been reported infrequently (approximately 0,8%) in association with Zoloft therapy. The abnormalities usually occurred within the first 1 to 9 weeks of drug treatment and promptly diminished upon drug discontinuation.
There have been rare reports of altered platelet function and/or abnormal clinical laboratory results in patients taking Zoloft. While there have been reports of abnormal bleeding or purpura in several patients taking Zoloft, it is unclear whether Zoloft had a causative role.
Hyponatraemia has been reported and appeared to be reversible when Zoloft was discontinued. Some cases were possibly due to inappropriate antidiuretic hormone secretion. The majority of reports were associated with older patients, and patients taking diuretics or other medications.
The concomitant use of Zoloft with a monoamine oxidase inhibitor (MAOI) is contra-indicated - see “Warnings”.
Special precautionary monitoring is advised with the following:
Protein bound medicines - In vitro protein binding studies performed with radiolabeled ³H-sertraline showed that sertraline is highly bound to serum proteins (98%) in the range of 20 to 500 ng/mL.
However, at up to 300 and 200 ng/mL concentrations, respectively, sertraline and N-desmethylsertraline did not alter the plasma protein binding of two other highly protein bound medicines, viz. warfarin and propranolol. However in three formal interaction studies with diazepam, tolbutamide and warfarin respectively, Zoloft was not shown to have significant effects on the protein binding of the substrate. (see also Other Interactions).
Serotonergic agents - Co-administration of Zoloft with other agents which enhance serotonergic neurotransmission, such as tryptophan or fenfluramine, should be avoided due to the potential for pharmacodynamic interaction.
Switching from other antidepressants or antiobsessional agents - There is limited controlled experience regarding the optimal timing of switching from other antidepressants or antiobsessional agents to Zoloft. Care and prudent medical judgement should be exercised when switching, particularly from long-acting agents such as fluoxetine. The duration of washout period which should intervene before switching from one selective serotonin reuptake inhibitor (SSRI) to another has not been established.
Other interactions - Co-administration of Zoloft (sertraline 200 mg daily) with diazepam or tolbutamide resulted in small, statistically significant changes in some pharmacokinetic parameters.
Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown.
Warfarin - Co-administration of sertraline 200 mg daily with warfarin resulted in a small but statistically significant increase in prothrombin time. Accordingly prothrombin time should be carefully monitored when Zoloft therapy is initiated or stopped.
No interactions reported with the following:
Zoloft has no effect on the beta-adrenergic blocking ability of atenolol. No interaction of sertraline 200 mg daily was observed with glibenclamide or digoxin.
Lithium - In placebo-controlled trials in normal volunteers, the combined administration of lithium and Zoloft did not alter lithium pharmacokinetics. It is recommended that plasma lithium levels be monitored following initiation of Zoloft therapy, so that appropriate adjustments to the lithium dose may be made if necessary. Co-administration with lithium may lead to a higher incidence of 5HT-associated side effects, resulting in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. Therefore, caution is recommended when co-administering sertraline with medications such as lithium, which may act via serotonergic mechanisms.
Medicines metabolised by cytochrome P450 (CYP) 2D6 - There is variability among antidepressants in the extent of clinically important inhibition of the drug metabolising isoenzyme CYP 2D6 and, in formal interaction studies, chronic dosing with sertraline 50 mg daily showed minimal elevation of steady state desipramine plasma levels (a marker of CYP 2D6 isoenzyme activity)
Medicines metabolised by other CYP enzymes - In vivo interaction studies have demonstrated that chronic administration of Zoloft 200 mg daily does not inhibit the CYP 3A3/4 mediated 6-beta hydroxylation of endogenous cortisol or the metabolism of carbamazepine or terfenadine.
The apparent lack of clinically significant effects of the chronic administration of Zoloft 200 mg daily on plasma concentrations of tolbutamide, phenytoin and warfarin suggests that Zoloft is not a clinically relevant inhibitor of CYP 2C9. The apparent lack of clinically significant effects of the chronic administration of Zoloft 200 mg daily on plasma concentrations of diazepam suggests that Zoloft is not a clinically relevant inhibitor of CYP 2C19. In vitro studies indicate that Zoloft has little or no potential to inhibit CYP 1A2.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
On the evidence available, Zoloft has a wide margin of safety in overdose. Serious sequelae have not been reported following overdoses of sertraline alone of up to 6 g. Although there have been no deaths reported when Zoloft was taken alone, deaths involving overdoses of Zoloft in combination with other medicines and/or alcohol have been reported. Therefore, any overdosage should be treated aggressively.
No specific therapy is recommended and there are no specific antidotes to sertraline.
Establish and maintain an airway, ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, a cathartic, may be as, or more, effective than emesis or lavage, and should be considered in treating overdosage. Monitoring of cardiac and vital signs is recommended, along with general symptomatic and supportive measures. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit.
ZOLOFT TABLETS 50 mg: White, film-coated, capsule-shaped tablets, with “Pfizer” coded on the one side and the trade name abbreviation “ZLT”and “50”on the other side, with a functional score line between the two.
ZOLOFT TABLETS 50 mg: Blister packs containing 30 tablets
Store below 30°C. Keep out of reach of children.
ZOLOFT TABLETS 50 mg : 32/1.2/0381
NAME AND BUSINESS ADDRESS OF APPLICANT
PFIZER LABORATORIES (PTY) LTD
102 Rivonia Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT
04 September 1998