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

Logo PARNATE (tablets)

SCHEDULING STATUS
S5

PROPRIETARY NAME
(and dosage form)

PARNATE (tablets)

COMPOSITION
Each tablet contains
tranylcypromine 10 mg as the sulphate

PHARMACOLOGICAL CLASSIFICATION
A 1.1 (Central analeptics)

PHARMACOLOGICAL ACTION
PARNATE, an anti-depressant, 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 week 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 patients with a previous history of hypersensitivity to tranylcypromine or any of PARNATE’S excipients.
In combination with other mono-amine oxidase inhibitors, such as furazolidone, isocarboxazid, nialamid, parghline 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 methylphenindate, ephedrine and over-the-counter medicines such as cold, hay fever and weigh-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.
This concomitant administration with pethidine and other narcotic analgesics has been associated with very severe reactions.
In concomitant administration with pethidine and other narcotic analgesics has been associated with very severe reactions.
In combination with dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause episodes of psychosis or bizarre behaviour.
In combination with SSRIs. There have been reports of serious, sometimes fatal reactions when MAOIs are given before, with, or shortly after discontinuation with some SSRIs. It is recommended that MAOIs are not used in combination with SSRIs.
In combination with cheese or other foods with high tyramine content. Hypertensive crises have sometimes occurred during PARNATE therapy after ingestion of foods with high tyramine content. In general, the patient should avoid protein foods in which aging or protein breakdown is used to increase flavour. In particular, patients should be instructed not to take foods such as cheese, sour cream, caviar, pickled herrings, liver, canned figs, raisings, 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, cherry and beer, 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 weight-reducing medicines that contain pressor agents. They should also be advised not to consume excessive amount of caffeine in any form.
PARNATE should not be administered to any patient with cerebrovascular or cardiovascular disease, a history of recurrent or frequent headaches, or to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease or hypertension.
PARNATE should not be used in patients with known liver damage or blood dyscrasia.
PARNATE should not be used in the presence of phaeochromocytoma, or if it is suspected, as such tumors secrete pressor substances.
Patients with impaired renal function, since there is a possibility of cumulative effects in such patients.
Safety in pregnancy and lactation has been established.

WARNINGS:
Exercise caution when giving PARNATE with guanethidine, reserpine, other hypotensive agents, barbiturates, anti-parkinsonism agents and clomipramine hydrochloride (see Special Precautions).
Administer with great care to elderly or agitated patients because of the possibility of existing cerebral sclerosis with damaged blood vessels.
PARNATE should be used with caution in diabetic patients as glucose metabolism may be altered or requirements of hypoglycaemics changed.
Use with caution in epileptic patients since PARNATE may influence the incidence of seizures and may therefore affect antiepileptic requirements.
PARNATE should be used with great care in patients with hyperthyroidism because of increased sensitivity to pressor amines.
MAO inhibitors may have the capacity of suppress anginal pain that would otherwise serve as a warning of myocardial ischaemia.
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.
The patient should also be warned about the possibility of hypotension and faintness, as well as drowsiness sufficient to impair performance of potentially hazardous tasks such as driving a car or operating machinery.

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 electroconvulsive 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
The most frequently seen side effect is insomnia. Less frequent cases of dizziness, palpitation, weakness, dry mouth, fatigue, drowsiness, constipation and other gastrointestinal disturbances (including nausea and vomiting), have been reported.
Palpitations or unusually frequent headaches, unaccompanied by paroxysmal hypertension, may possibly be dose-related in some patients. Such symptoms may respond to reduction of dosage. If improvement is not rapid, this medicine should be discontinued.
Hypotension, which may be postural, has been observed during PARNATE therapy. Syncope has been less frequently seen. Dosage should not be increased in the presence of hypotension. This side effect is usually temporary, but if it persists, the drug should be discontinued. The blood pressure will then return rapidly to pre-treatment level.
Overstimulation, which may include increased anxiety and agitation, and manic symptoms, may occur. Psychotic episodes, with hypomanic behaviour, confusion, and hallucinations, may be induced in susceptible persons. Reduction of the dose is indicated.
Haematological disorders including anemia, leucopenia, agranulocytosis, and thrombocytopenia have been reported.
Oedema, skin rashes, and micturation difficulty have infrequently occurred.
Convulsions, sexual disturbances, and weight gain with inappropriate appetite may also occur. Jaundice has been reported and, on rare occasions, fatal progressive hepatocellular necrosis.
The most important adverse reaction associated with PARNATE is the occurrence of hypertensive crises which have sometimes been fatal. These crises may occur when PARNATE is given simultaneously with some other medicines, or cheese and certain foods (See Contraindications, Warnings, Special Precautions) and are characterized 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 hemorrhage, but can equally be associated with actual intracranial bleeding, as in other conditions where a sudden rise in blood pressure occurs. 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 of frequent headache during tranylcypromine therapy. 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.). Reserpine should not be used. Care should be taken to administer phentolamine slowly in order to avoid producing an excessive hypotensive effect. 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.

SPECIAL PRECAUTIONS:
Mono-amine oxidase inhibitors have a prolonged action, so patients should not take any of the food or medicines known to cause reactions for at least 14 days after stopping treatment.
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: PARNATE 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.
Patients should be warned to avoid cheese, protein extracts such as Marmite, and the other prohibited dietary items while taking PARNATE. (Refer to contraindications) Patients should be warned against self-medication with proprietary medicines such as cold, hay fever weight-reducing medicines that contain pressor agents. They should also be advised not to consume excessive amount of caffeine in any form.
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.

INTERACTIONS:
Exercise caution, when giving PARNATE with the following medicines:
Hypotensive and hypertensive reactions have been suggested with different agents.
Fuanethidine [Guanethidine - Ed.], as its action may be antagonized
Reserpine, as hyperactivity may occur
Alpha-methyldopa, since the combination may give rise to central excitation
Other hypotensive agents, because of the possibility of addictive 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.

PARNATE is contraindicated in combination with other MAO inhibitors, dibenzazepine derivatives, sympathomimetics, SSRi’s and dextromethorphan. (Refer to Contraindications)

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 (hypotention 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, close observation of vital signs and steps to counteract specific symptoms as they occur since mono-amine oxidase inhibition may persist. They 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. Mephentermine or metaraminol may be required if marked refractory hypotension occurs.
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 with the * la check SK&F monogram on the face.

PRESENTATION
PARNATE tablets are available in containers of 50 and 28.

STORAGE INSTRUCTIONS
PARNATE tablets should be stored below 25ºC in a dry place and dispensed in moisture-proof containers.
Keep out of reach of children.

REGISTRATION NUMBER (OR REFERENCE NUMBER)
PARNATE Tablets: B. 1034 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF APPLICANT
PHARMAFRICA (PTY) LTD
33 Hulbert Road
New Centre
Johannesburg
2001

DATE OF PUBLICATION OF THIS PACKAGE INSERT
25.08.1988

Updated on this site: May 2014
Source: Pharmaceutical Industry

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2014