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

Logo ‘PARNATE’Tablets 10 mg

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

‘PARNATE’Tablets 10 mg

COMPOSITION:
Each tablet contains
tranylcypromine 10 mg as the sulphate.

PHARMACOLOGICAL CLASSIFICATION:
A.1.2 Psychoanaleptics (antidepressants).

PHARMACOLOGICAL ACTION:
‘Parnate’, an antidepressant, is a mono-amine oxidase inhibitor. It is believed to act by increasing the levels of amines in the brain, thought to be low in depression.

INDICATIONS:
‘Parnate’is indicated in depression. It is not recommended for use in mild depressive states resulting from temporary situational difficulties.

CONTRA-INDICATIONS:
Because the effect of many antidepressant drugs may persist for several days, do not commence, Parnate, therapy within less than two weeks of discontinuing treatment with such medicines. Then use half the normal dosage for the first week. Similarly, allow two weeks to elapse between the discontinuance of ‘Parnate’and the administration of any other medicine that is contra-indicated with ‘Parnate’.

‘Parnate’is Contra-Indicated:
In combination with other mono-amine oxidase inhibitors, such as furazolidone, isocarboxazid, nialamid, pargyline and phenelzine.
In combination with dibenzazepine derivatives, such as amitriptyline, desipramine, imipramine, nortriptyline, protriptyline and carbamazepine, as these combinations may induce hypertensive crises or severe convulsive seizures.
In combination with sympathomimetics, including amphetamines, fenfluramine and methylphenidate, ephedrine and over-the-counter medicines such as cold, hay fever and mass-reducing preparations that contain vasoconstrictors. Also with methyldopa, dopamine, levodopa and tryptophane, as they may result in potentiation, precipitating hypertension, severe headache, and hyperpyrexia; cerebral haemorrhage may occur. The concomitant administration with pethidine and other narcotic analgesics has been associated with very severe reactions.
In combination with cheese or other foods rich in pressor amines. Hypertensive crises have sometimes occurred during ‘Parnate’ therapy after ingestion of foods with a high tyramine content. In general, the patient should avoid protein foods in which ageing or protein breakdown is used to increase flavour. In particular, patients should be instructed not to take foods such as cheese, sour cream, pickled herrings, liver, canned figs, raisins, bananas or avocados (particularly if overripe), chocolate, soy beans, the pods of broad beans, yeast extracts, or meals prepared with tenderizers. Alcoholic drinks, which may contain significant amounts of tyramine, especially red wine such as Chianti, should also be avoided.
It is important, therefore, that patients be warned to avoid cheese, protein extracts such as Marmite, and the other prohibited dietary items while taking ‘Parnate,. Patients should be warned against self-medication with proprietary medicines such as cold, hay fever or mass-reducing medicines that contain pressor agents. They should also be advised not to consume excessive amounts of caffeine in any form.
In patients with cerebrovascular or cardiovascular disease, liver damage or blood dyscrasias. ‘Parnate’ should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease and hypertension. Administer with great care to elderly or agitated patients because of the possibility of existing cerebral sclerosis with damaged blood vessels, and patients with diminished renal function.
‘Parnate, should not be used in patients with known liver damage or blood dyscrasia.
In phaeochromocytoma. ‘Parnate’should not be used in the presence of phaeochromocytoma, or if it is suspected, as such tumors secrete pressor substances.

DOSAGE AND DIRECTIONS FOR USE:
Adults only.
Begin with 20 mg a day –given as 10 mg in the morning and in the afternoon. If there is no satisfactory response after two weeks, add one more tablet at midday. Continue this dosage for at least a week. When satisfactory response is established dosage may be reduced to a maintenance level. Some patients will be maintained on 20 mg per day, some will need only 10 mg daily. If no improvement occurs, continued administration is unlikely to be beneficial.
When given together with a tranquillizer, the dosage of ‘Parnate’is not affected. When the drug is given concurrently with electrocomulsive therapy, the recommended dosage is 10 mg twice a day during the series and 10 mg a day afterwards as maintenance therapy.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Adverse effects commonly associated with monoamine oxidase inhibitors include postural hypotension and attacks of dizziness. Other common side-effects include drowsiness, weakness and fatigue, dryness of mouth, constipation and other gastro-intestinal disturbances (including nausea and vomiting), and oedema. Agitation and tremors, insomnia and restless sleep, blurred vision, difficulty in micturition, convulsions, skin rashes, leucopenia, sexual disturbances, and mass gain with inappropriate appetite may also occur. Psychotic episodes, with hypomaniac behaviour, confusion, and hallucinations, may be induced in susceptible persons. Jaundice has been reported and, on rare occasions, fatal progressive hepatocellular necrosis.
Severe hypertensive reactions, sometimes fatal, may occur if a mono-amine oxidase inhibitor is given simultaneously with some other medicines or cheese and certain other foods (see Precautions).
These crises are characterised by some or all of the following symptoms: occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea or vomiting, sweating with early pallor followed later by flushing. Either tachycardia or bradycardia may be present; and associated mydriasis may also occur. This headache, together with pain and stiffness in the cervical muscles, may mimic subarachnoid haemorrhage, but can equally be associated with actual intracranial bleeding, cases of such bleeding have been reported, some of which have been fatal. Acute cardiac failure may result.

Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headache during ‘Parnate’ therapy. These signs may be prodromal of a hypertensive reaction. Patients should be instructed to report promptly the occurrence of headache or other symptoms.

Recommended treatment in hypertensive reactions:
If a hypertensive reaction occurs, ‘Parnate’should be discontinued and therapy to lower blood pressure should be instituted immediately, if indicated.
Headache tends to abate as blood pressure falls. On the basis of present evidence, phentolamine is recommended. (The dosage reported for phentolamine is 5 mg i.v.) Care should be taken to administer phentolamine slowly in order to avoid producing an excessive hypotensive effect. Reserpine should not be used. Fever should be managed by means of external cooling. Other symptomatic and supportive measures may be desirable in particular cases. Acute symptoms generally subside within 24 hours.

Precautions:
Mono-amine oxidase inhibitors have a prolonged action, so patients should not take any of the foods or medicines known to cause reactions for at least 14 days after stopping treatment.

Exercise caution:
When giving ‘Parnate’with the following medicines:
Hypotensive and hypertensive reactions have been suggested with different agents.
Guanethidine, as its action may be antagonised.
Reserpine, as hyperactivity may occur.
Alpha-methyldopa, since the combination may give rise to central excitation.
Other hypotensive agents, because of the possibility of additive hypotensive effects.
Barbiturates and possibly other hypnotics, as their action may be prolonged or potentiated.
Anti-Parkinsonism agents, as the combination may result in potentiation, with profuse sweating, tremulousness, and rise in body temperature.

In diabetes: Some mono-amine oxidase inhibitors have contributed to hypoglycaemic episodes in diabetic patients receiving insulin or oral hypoglycaemic agents. ‘Parnate’ should therefore be used with caution in diabetics under treatment with these medicines.

In epileptic patients: Tranylcypromine may influence the incidence of seizures and affect anticonvulsant requirements.
Alcohol metabolism may be altered and its effect enhanced.
Patients liable to take charge of vehicles or other machinery should be warned that ‘Parnate’, may modify behaviour and state of alertness.

In surgery: It is advisable wherever possible to discontinue ‘Parnate’therapy at least 14 days before surgery because of possible interference with the action of certain anaesthetics and analgesics.

In pregnancy: Use in pregnancy requires that the potential benefits be weighed against its possible hazards to mother and child. Animal reproductive studies show that ‘Parnate’ passes through the placental barrier into the foetus of the rat. It also passes into milk of the lactating dog.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms of overdosage may not occur for some hours after ingestion. They include agitation with hyperactivity and hallucinations, tachycardia, hypertension sometimes with severe headache (hypotension may also develop), hyperreflexia and spasticity, profuse sweating and hyperthermia, (hypothermia may also develop), dilated pupils, urinary retention, coma, convulsions, and signs of peripheral collapse. The acute effects of mono-amine oxidase inhibitor overdosage may be followed by the delayed effects of mono-amine oxidase inhibition which do not develop until several days later.

Symptoms: The characteristic symptoms that may be caused by overdosage are usually those described under adverse reactions. Tachycardia, sweating and hyperpyrexia with restlessness and excitement are usually produced. Depression, stupor or coma may, however, be present or develop. Blood pressure may be raised, but hypotension may supervene.

Treatment: Gastric lavage is helpful if performed early. Treatment should normally consist of general supportive measures, dose observation of vital signs and steps to counteract specific symptoms as they occur since mono-amine oxidase inhibition may persist. The management of hypertensive reactions is described earlier. External cooling is recommended if hyperpyrexia occurs. Barbiturates have been reported to help myoclonic reactions, but frequency of administration should be controlled carefully because ‘Parnate’may prolong barbiturate activity. When hypotension requires treatment, the standard measures for managing circulatory shock should be initiated. If pressor agents are required, noradrenaline is the most suitable, however, its action may be potentiated, and the rate of infusion should be regulated by careful observation of the patient. It has been suggested that haemodialysis may be of value in very severely poisoned patients.

IDENTIFICATION:
‘Parnate’tablets are circular bi-convex, sugar-coated rose-coloured tablets.

PRESENTATION:
‘Parnate’tablets are available in containers of 50 and 250.

STORAGE INSTRUCTIONS:
Store below 25°C in a dry place and dispense in moisture-proof containers.
KEEP OUT OF REACH OF CHILDREN.

REFERENCE NUMBER:
B.1034 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd.
6 Carey Street,
Wynberg Ext. 6,
Johannesburg 2090

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
25.08.1988

PO256

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