INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo SERLIFE 50 Tablets
SERLIFE 100 Tablets
SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

SERLIFE 50 Tablets
SERLIFE 100 Tablets

COMPOSITION
Serlife 50 Tablets
Each film-coated tablet contains
Sertraline hydrochloride
equivalent to sertraline 50 mg
Sugar free.

Serlife 100 Tablets
Each film-coated tablet contains
Sertraline hydrochloride
equivalent to sertraline 100 mg
Sugar free.

PHARMACOLOGICAL CLASSIFICATION
A 1.2. Psychoanaleptics (Antidepressants)

PHARMACOLOGICAL ACTION
Mechanism of action
Sertraline, a naphthaleneamine derivative, is a selective serotonin reuptake inhibitor (SSRI). Sertraline has only weak effects on neuronal reuptake of norepinephrine and dopamine. Chronic administration of sertraline in animals has resulted in downregulation of post-synaptic beta-adrenergic receptors. Sertraline's inhibition of serotonin reuptake enhances serotonergic transmission, which results in subsequent inhibition of adrenergic activity in the locus ceruleus. Sertraline has no specific affinity for adrenergic (alpha1, alpha2, or beta) receptors, muscarinic cholinergic receptors, gamma-aminobutyric acid receptors, dopaminergic receptors, histaminergic receptors, serotonergic (5HT1A, 5HT1B, 5HT2) or benzodiazepine receptors. Sertraline does not inhibit monoamine oxidase.
Pharmacokinetics
After oral administration, sertraline is slowly absorbed. It undergoes rapid first pass metabolism. The Cmax and the AUC are proportional to the dose over the range of 50-200 mg of sertraline, demonstrating linear pharmacokinetics. Sertraline undergoes extensive first pass metabolism in the liver. After once-daily dosing of sertraline, steady state plasma concentrations are reached in about 7 days in adult subjects and after 2-3 weeks in older patients. The primary initial pathway of sertraline metabolism is N-demethylation to form N-desmethylsertraline, which is substantially less active than the parent compound, exhibiting only about 1/8th of its activity. Both sertraline and desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation. The elimination half-lives of sertraline and desmethylsertraline are 24-26 and 62-104 hours respectively. Both sertraline and its metabolite, desmethylsertraline are extensively distributed into the tissues, the volume of distribution for the parent compound being about 76 L/kg. The plasma protein binding is greater than 98%. About 40-45% of an administered radioactive dose was recovered in the urine within 9 days with less than 0,2% recovered unchanged; faecal recovery is 40-45%, including 12-14% unchanged sertraline. The clearance of sertraline is about 38 + 14 mL/min/kg in healthy, young subjects which is decreased by about 40% in older individuals. Clearance of desmethylsertraline is also decreased in older men but not in older women.
The pharmacokinetics of sertraline have not been studied in patients with significant renal impairment.
Since sertraline is extensively metabolised in the liver, its metabolism may be altered in hepatic function impairment. Therefore caution is advised when sertraline is administered to such patients; a lower dose or less frequent dosing should be considered.

INDICATIONS
Serlife is indicated for the treatment of symptoms of major depressive illness such as single episodes and recurrence of further depressive episodes.
Sertraline is also indicated for the treatment of obsessive compulsive disorder (OCD).

CONTRA-INDICATIONS
Serlife is contra-indicated in patients who have shown hypersensitivity to any components of the product.
Concomitant use of Serlife in patients taking monoamine oxidase inhibitors (MAOIs) is contra-indicated (see Warnings).
Pregnancy and lactation as safety has not been established.

WARNINGS
Severe adverse reactions including the serotonin syndrome may occur if Serlife is administered with a monoamine oxidase inhibitor (MAOI). Although no clinical data are available demonstrating the effects of the combined use of Serlife and monoamine oxidase inhibitors (MAOI), it is prudent to avoid their combined use until specific data are available, as experience suggests that the combination may produce a potentially lethal serotonin syndrome. A wash-out period of at least 14 days should elapse between discontinuation of one medication and initiation of the other.
Serlife should be used with caution in patients with epilepsy or a history of similar disorders and should be avoided if epilepsy is poorly controlled.
Renal excretion is a minor route of elimination of sertraline. However, sertraline pharmacokinetics have not been studied in patients with renal impairment and the safety of Serlife in patients with severe renal impairment and the dose adjustments required, if any, have not been established. Caution should be exercised when Serlife is administered to such patients.
Sertraline is extensively metabolised in the liver. A lower or less frequent dose may be required in patients with significant liver function impairment.
While switching from other antidepressant or anti-obsessional medicines to Serlife, care and prudent medical judgement should be exercised since there is limited controlled experience.
No data are available on the concomitant use of Serlife with serotonergic medicines such as sumatriptan, tryptophan or fenfluramine. Therefore, these medicines should not be used concomitantly.
The possibility of a suicide attempt is inherent in patients with depressive illness. Close supervision of high risk patients should accompany the administration of Serlife.
There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and sertraline.
Clinical studies with sertraline have clearly shown a lack of any adverse effect on the psychomotor performance. However, since antidepressant or anti-obsessional medicines may impair the abilities required to perform potentially hazardous tasks such as driving a car or operating machinery, the patient should be cautioned accordingly.
There have been reports of activation of mania/hypomania.
Significant weight loss, although less frequently reported with the use of sertraline, may be undesirable in some patients.
Mean decreases of approximately 7% in the serum uric acid have been reported with sertraline use. However, the clinical significance of this finding is not known and there have been no reports of acute renal failure with sertraline.
Sertraline has not been shown to cause sedation or alter psychomotor performance.
Electrocardiographic studies have shown that sertraline does not cause any significant ECG abnormalities. However, 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 concomitant use of Serlife and alcohol in depressed patients is not recommended.

INTERACTIONS
Serlife has not been shown to alter alcohol metabolism and does not appear to potentiate cognitive and psychomotor effects of alcohol, or carbamazepine or haloperidol or phenytoin in normal subjects. Concomitant use of Serlife and alcohol is not recommended.
Small but statistically significant changes in some pharmacokinetic parameters of diazepam and tolbutamide have been observed when these medicines were co-administered with Serlife.
The clearance of Serlife is significantly decreased by cimetidine. However, its clinical significance is unknown.
Prothrombin time should be monitored in patients receiving Serlife and warfarin concomitantly, since a statistically significant increase in prothrombin time has been observed in such patients.
Studies have shown no interaction of sertraline with digoxin or glibenclamide.
The SSRIs have been reported to interact with medicines metabolised by cytochrome P450. There is considerable variability in the extent to which these medicines inhibit isozyme P450 2D6. In this regard, no significant interactions of sertraline have been reported. Sertraline has shown minimal elevation of desipramine plasma concentration (a marker of isozyme P450 2D6 activity). The carbamazepine plasma concentration (a marker of isozyme P450 3A4 activity) were not altered following concomitant administration with sertraline.
The beta adrenergic blocking activity of atenolol is not affected by Serlife.
The pharmacokinetics of lithium are not altered by Serlife. However, a careful monitoring of plasma lithium concentration is recommended for making adjustments in lithium doses, if required. Caution is advised when sertraline is administered with medicines such as lithium which may act via serotonergic mechanisms since a higher incidence of serotonin associated side-effects may occur.

PREGNANCY AND LACTATION
Pregnancy: Adequate and well-controlled studies in pregnant women have not been performed. Animal reproduction studies have not shown any evidence of teratogenicity or embryotoxicity with sertraline. However, since animal reproduction studies are not always predictive of human response, Serlife should be used during pregnancy only if the potential benefits outweigh the risks. Women of childbearing potential who are on Serlife should employ an adequate method of contraception.
Lactation:Limited data concerning sertraline levels in breast milk are available, hence use of Serlife in breast feeding mothers is not recommended.

DOSAGE AND DIRECTIONS FOR USE
Serlife tablets should be given as a single daily dose with or without food.
Adults
Depression: The starting dose is 50 mg daily and the usual antidepressant dose is 50 mg daily. In patients with incomplete response but good toleration at lower doses, dosage adjustments should be made in 50 mg increments over a period of 2 weeks to a maximum of 200 mg daily.
Obsessive Compulsive Disorder:The minimum effective dose is 50 mg daily and doses above 100 mg did not have any additional benefit. The onset of therapeutic effect may be seen within 7 days, although 2-4 weeks (and even longer in OCD) are usually necessary for full activity.
Use in patients with renal or hepatic impairment
Serlife should be used with caution in patients with renal and hepatic impairment.
Use in children
The safety and efficacy of Serlife have not been established in children.
Use in the elderly
No special precautions are required. The usual adult dose is recommended.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
The side-effects that have been reported with the use of sertraline include:
Gastro-intestinal: Nausea, diarrhoea, dyspepsia.
Central nervous system: Dizziness, insomnia, somnolence.
Body as a whole: Tremor, increased sweating, dry mouth.
Others: Male sexual dysfunction (primary ejaculation delay).
Other adverse effects that have been observed in patients treated with sertraline with a frequency equal to or greater than that with placebo include:
Cardiovascular: Palpitation.
Nervous system: Headache, paresthesia, hypoesthesia, twitching, hypertonia.
Skin: Rash.
Gastro-intestinal: Constipation, vomiting, flatulence, anorexia, abdominal pain, increased appetite.
Body as a whole: Fatigue, fever, hot flushes, back pain, thirst, myalgia.
Psychiatric: Agitation, nervousness, anxiety, yawning, female sexual dysfunction, impaired concentration
Genito-urinary: Micturition frequency, micturition disorder, menstrual disorder.
Respiratory: Rhinitis, pharyngitis.
Special senses: Abnormal vision, tinnitus, taste perversion.
Laboratory abnormalities such as elevation in serum levels of transaminases (AST, ALT) (diminishing upon drug discontinuation) and reversible hyponatraemia have been reported with sertraline use. Most of the reports of hyponatraemia were associated with elderly patients, and those taking diuretics or other medicines concomitantly.
Special Precautions
Extrapyramidal symptoms and an aggravation of Parkinson's disease have been observed with SSRIs. Caution should be exercised when Serlife is administered to such patients and careful monitoring should be done. Withdrawal symptoms may occur if Serlife is discontinued abruptly. These include dizziness, sweating, nausea, insomnia, tremor, confusion, sensory disturbances, agitation and anxiety.
Caution in concurrent use of highly protein bound medicines with Serlife is recommended because of possible displacement of either medication from protein binding sites, leading to increased plasma concentrations of the free medicine and increased risk of adverse effects.
Paediatics: Safety and efficacy of Serlife in paediatric patients have not been established.
Geriatrics: No geriatrics-specific problems have been documented to date with the use of Serlife.

KNOWN SYMPTOMS OF OVER DOSAGE AND PARTICULARS OF ITS TREATMENT
Sertraline has a wide margin of safety. No serious sequelae have been reported following sertraline overdose as high as 6 g. Although there have been no reports of death due to sertraline-only overdose, fatalities have occurred in combination with other medicines and/or alcohol. No specific therapy is recommended and there is no specific antidote to Serlife. Treatment is essentially symptomatic and supportive, possibly including:
• Establishing and monitoring airway
• Ensuring adequate oxygenation and ventilation
• Monitoring cardiac function and vital signs
• Administering activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or gastric lavage
Dialysis, forced diuresis, haemoperfusion and exchange transfusions are unlikely to be of benefit due to Serlife's large volume of distribution and high degree of protein binding.

IDENTIFICATION
Serlife 50 Tablets: White, film-coated, capsule shaped tablets, debossed with `50' on one side and a breakline on the other.
Serlife 100 Tablets: White, film-coated, capsule shaped tablets, debossed with `100' on one side and a breakline on the other.

PRESENTATION
Serlife 50 Tablets: Tablets are packed in blister strips. Carton containing 30 or 100 tablets.
Serlife 100 Tablets: Tablets are packed in blister strips. Carton containing 30 or 100 tablets.
The blister material is a white, opaque PVC film with a backing of aluminium foil.

STORAGE INSTRUCTIONS
Store below 25°C, protected from moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS
Serlife 50 Tablets: 36/1.2/0272
Serlife 100 Tablets: 36/1.2/0273

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
RANBAXY (SA) (PTY) LTD
Third Floor
Outspan House,
1006 Lenchen Avenue North
Centurion

DATE OF PUBLICATION OF THE PACKAGE INSERT
September 2003

New addition to this site: March 2004
Source: Pharmaceutical Industry


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