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

Logo SAROTEN® RETARD 25 mg Capsules
SAROTEN® RETARD 50 mg Capsules

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

SAROTEN® RETARD 25 mg Capsules
SAROTEN® RETARD 50 mg Capsules

COMPOSITION:
Each capsule contains
amitriptyline hydrochloride in a sustained release formulation corresponding to 25 mg or 50 mg amitriptyline.

PHARMACOLOGICAL CLASSIFICATION:
A 1.2 Psychoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION:
Amitriptyline is a tricyclic antidepressant. Amitriptyline inhibits serotonin and noradrenaline uptake equally. It has anticholinergic, antihistaminergic and sedative properties and it potentiates the effects of catecholamines.
The antidepressive, mood-elevating effect usually sets in after 2-4 weeks, the sedative action is not delayed.
Pharmacokinetics
Amitriptyline as such is rapidly absorbed but owing to the sustained release from SAROTEN RETARD capsules amitriptyline only becomes available for absorption slowly. This results in a rather flat serum concentration curve. As SAROTEN RETARD is administered in the evening 3-4 hours before bedtime the highest serum concentrations of amitriptyline are present in the early hours of the morning owing to the slow absorption rate of this formulation. The bioavailability after an oral dose of amitriptyline is about 40% (first pass metabolism). The volume of distribution is about 22 L/kg. The plasma protein binding is about 95%. The biological half-life is 12-24 hours and clearance about 0,7 L/min. Amitriptyline is metabolised by N-demethylation, 10-hydroxylation and N-oxidation. The active substance, nortriptyline, is formed by demethylation. The therapeutic serum level (the sum of amitriptyline and nortriptyline) is 100-250 ng/mL corresponding to 360-900 nmol/L. Amitriptyline and nortriptyline cross the placental barrier and are excreted in human breast milk in concentrations similar to those in serum.
Amitriptyline is excreted in the urine mainly in the form of its metabolites, free or as glucuronic acid conjugates.

INDICATIONS:
Major depressive illnesses which include endogenous depression, involutional melancholia, masked depression and reactive depression. Secondary depression which includes depression associated with alcoholism and depression associated with schizophrenia.

CONTRA-INDICATIONS:
The immediate recovery phase after myocardial infarction. Untreated narrow angle glaucoma. Acute alcohol, barbiturate or opiate intoxication. Should not be given to patients receiving monoamine oxidase (MAO) inhibitors or for at least 14 days after their discontinuation. Safety in pregnancy has not been established.

WARNINGS:
As drowsiness and diminished alertness are common in the early stages of treatment, patients should be warned not to drive, operate dangerous machinery, or climb dangerous heights until it has been established that their alertness is not impaired. In these situations impaired decision making could lead to accidents.
Special warning:
This medicine should at all times be kept out of reach of children, as even small doses may be fatal to them.

DOSAGE AND DIRECTIONS FOR USE:
Initially 1 capsule of 50 mg 3-4 hours before bedtime. After 1 week the dose may be increased to 2-3 capsules (100-150 mg) in the evening. When satisfactory improvement has been reached, dosage should be gradually reduced to the lowest amount that will maintain relief of symptoms, usually 1-2 capsules (50-100 mg) in the evening.
For elderly patients over 60 years of age, the initial dosage is 1 capsule of 25 mg 3-4 hours before bedtime. After 1 week the dosage may be increased to 2-3 capsules (50-75 mg) in the evening. When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms, usually 1-2 capsules (25-50 mg) in the evening.
In endogenous depression, treatment with antidepressants must be continued as long as 4-6 months in manic depressive illness (bipolar affective disorder). Prolonged treatment possibly for years can have preventive effects on recurrent nonbipolar depression. (See also special precaution concerning manic depressives).

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Anticholinergic - notably dryness of the mouth, blurred vision, disturbances of accommodation, tachycardia, constipation and urinary retention. If these side-effects are severe the dosage should be reduced or the medication withdrawn.
Central nervous system and neuromuscular - drowsiness, weakness, fatigue, disturbed concentration and dizziness. Somnolence, disorientation, confusion states, tremor and convulsions may arise, especially when high initial doses are administered.
Cardiovascular - tachycardia, arrhythmias, orthostatic hypotension, ECG changes in the form of isoelectric or diphasic T1 or a negative T2. Bundle branch block has occurred. The ECG changes usually disappear when the antidepressant drug is withdrawn.
Note! Elderly patients are particularly liable to experience side-effects of cyclic antidepressants and, in general, lower doses are recommended for these patients and the initial dose should be increased under close supervision.
Special precautions:
In manic-depressives the use of antidepressants may precipitate a shift towards the manic phase. The medicine must be withdrawn immediately should the patient show signs of entering a manic phase, and replaced by a suitable neuroleptic.
When treating depressive states in schizophrenics, SAROTEN RETARD should be used in combination with a neuroleptic to prevent exacerbation of hallucinations and paranoid delusions.
In patients with symptoms suggestive of prostatic hypertrophy, the drug should be used with caution as it may precipitate urinary retention. In cardiac disease regular cardiological and electrocardiographic examinations are advised, as cyclic antidepressants may produce cardiovascular adverse effects.
Epilepsy, hepatic insufficiency and narrow angle glaucoma may be aggravated.
Attacks of intermittent blurring of vision, rainbow vision and ocular paid call for immediate opthalmological examination to rule out glaucoma before the medication can be continued.
If allergic skin reactions occur the drug should be withdrawn.
There is an increased risk of suicide when the depression begins to subside because the disinhibitory effect may set in before the antidepressant action.
Interactions
Amitriptyline may enhance the response to alcohol, barbiturates and other CNS depressants.
Simultaneous administration of MAO inhibitors may cause hypertensive crises.
The effects of anticholinergics are potentiated and concomitant use of these should be avoided.
The effects of the direct-acting sympathomimetic agents, adrenaline and noradrenaline, are enhanced and the use of local anaesthetics containing these should be avoided.
The antihypertensive effect of clonidine, bethanidine and guanethidine may be reduced.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage and poisoning may result in CNS depression or excitation, severe anticholinergic effects and cardiotoxicity.
The following symptoms and signs are characteristic of acute overdosage:
Drowsiness, restlessness, agitation, ataxia, stupor, coma, pyrexia, palpitations, tachycardia, cardiac arrhythmias, hypotension and in severe cases respiratory depression. Epileptiform seizures may occur. Mixed poisoning with other central nervous depressants is not uncommon.
Treatment is symptomatic and supportive. Gastric lavage should be carried out immediately. Measures aimed at supporting the respiratory and cardiovascular systems should be instituted. Close monitoring of the cardiac function for 3-5 days is advisable.

IDENTIFICATION:
25 mg capsules : Cream-yellow opaque body and brick coloured cap, containing cream coloured pellets.
50 mg capsules : Brick coloured opaque body and cap, containing cream coloured pellets.

PRESENTATION:
Capsules 25 mg:        30
Capsules 50 mg:        30

STORAGE INSTRUCTIONS:
Store below 30°C in a dry place.
Keep out of reach of children.

REGISTRATION NUMBER:
25 mg :        F/1.2/123
50 mg :        F/1.2/124

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
H. Lundbeck (Pty) Ltd
P O Box 2357
Randburg
2125

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
December 1987

Updated on this site: May 2000

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2000