PARNATE

What it is

Parnate is tranylcypromine sulfate 10 mg supplied as a film coated tablet. Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor (MAOI) with a rapid onset of activity. It increases the concentration of adrenaline (epinephrine), noradrenaline (norepinephrine), and serotonin in storage sites throughout the nervous system, and in theory, this increased concentration of monoamines in the brainstem is the basis for its antidepressant activity.

Approved indications

— Treatment of symptoms of depressive illness, especially where treatment with other types of antidepressants has failed. Parnate is not recommended for use in mild depressive states resulting from temporary situational difficulties.

Dosing overview

Adults begin with 20 mg a day, given as 10 mg in the morning and 10 mg in the afternoon. If there is no satisfactory response after two weeks, add one more tablet at midday and continue this dosage for at least a week. A dosage of 3 tablets a day should only be exceeded with caution, and the maximum dose should not exceed 30 mg per day. When a satisfactory response is established, dosage may be reduced to a maintenance level, with some patients maintained on 20 mg per day and some needing only 10 mg daily. Parnate is not indicated for children under 18 years of age.

Key safety warnings

The most important adverse effect associated with Parnate is the occurrence of hypertensive crises which have sometimes been fatal. Cases of sudden paroxysmal rise in blood pressure have occurred, notably in association with foods containing tyramine. Hypertensive crises have sometimes occurred during Parnate therapy after ingestion of foods with a high tyramine content. Patients should avoid matured cheese and protein extracts such as Marmite, Vegemite, Bonox and Bovril; protein foods in which ageing or protein breakdown is used to increase flavour; the pods of broad beans, sauerkraut, pickled herring, sour cream, soy sauce, avocado pears, yeast extracts and banana skins; and alcoholic drinks, which may contain significant amounts of tyramine, especially red wine such as Chianti. The risk of suicide attempt is inherent in depression and may persist until significant remission occurs; patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviour whether or not they are taking antidepressant medications; and the risk is increased in patients less than 25 years old. All patients should be closely monitored for clinical worsening of suicidality, especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases.

Contraindications

Parnate is contraindicated in patients with a known hypersensitivity to tranylcypromine or to any of the excipients. Parnate is contraindicated in combination with other MAOIs, such as phenelzine and moclobemide, furazolidone, iproniazid, isocarboxazid, nialamide, pargyline, and procarbazine hydrochloride; at least 2 weeks should elapse after stopping a previous MAOI before starting Parnate at a reduced dose; at least a week should elapse between the discontinuance of tranylcypromine and the administration of another MAOI; and hypertensive crises or severe convulsive seizures may occur in patients receiving such combinations. Parnate should not be administered 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 the presence of phaeochromocytoma, or if it is suspected, as such tumours secrete pressor substances. <cite index index="1-71">Parnate should not be used in patients with a history of liver disease or in those with abnormal liver function tests.</cite> Parnate should not be administered to any patient beyond 60 years of age because of the possibility of existing cerebral sclerosis with damaged blood vessels. Parnate is contraindicated in combination with fluoxetine and other SSRIs and SNRIs, as serious and sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability and mental status changes have been reported; Parnate should not be used in combination with fluoxetine or its congeners; at least five weeks should elapse between discontinuation of fluoxetine and initiation with Parnate; and fluoxetine should not be given within two weeks of Parnate discontinuation. Parnate should not be given together with or within two weeks of treatment with other SSRIs (e.g. paroxetine, sertraline) and SNRIs (e.g. venlafaxine).

PBS listing

Parnate 10 mg tablet is listed on the PBS with 2 items, unrestricted and restricted restriction types, at an ex-manufacturer price of A$35.64.

Regulatory history

Parnate tranylcypromine (as sulphate) 10 mg film coated tablet was first listed on the ARTG on 21 October 2010.