Consumer medicine information

Parnate tablets

Tranylcypromine

BRAND INFORMATION

Brand name

Parnate

Active ingredient

Tranylcypromine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Parnate tablets.

WHAT IS IN THIS LEAFLET

This leaflet answers some of the common questions about Parnate. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Parnate against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

WHAT PARNATE IS USED FOR

Parnate is used to treat symptoms of depression, especially if treatment with other types of antidepressants has failed. There are many different types of medicines used to treat depression. Parnate belongs to a group of medicines called monoamine oxidase inhibitor (MAOI) antidepressants. It contains the active ingredient tranylcypromine.

Depression is longer lasting or more severe than the ‘low moods’ that everyone has from time to time. It is thought to be caused by a chemical imbalance in parts of the brain. The imbalance affects your whole body and can cause emotional and physical symptoms. You may feel low in spirit, lose interest in usual activities, be unable to enjoy life, have poor appetite or overeat, have disturbed sleep, often waking up early, low energy and feel guilty over nothing.

Parnate corrects the chemical imbalance and helps relieve the symptoms of depression. It is not recommended for the ‘low moods’ that everyone has from time to time due to the stress or sadness of everyday life.

Your doctor may have prescribed Parnate for another use.

Ask your doctor if you have questions about why Parnate has been prescribed for you.

Parnate is available only with a doctor’s prescription.

BEFORE YOU TAKE PARNATE

When you must not take it

Do not take Parnate if you have an allergy to:

  • Parnate or any other medicine containing tranylcypromine
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take Parnate if you have taken it or any other MAOI medication (e.g. phenelzine, moclobemide, furazolidone, iproniazid, isocarboxazid, nialamide, pargyline, procarbazine hydrochloride) before and became unwell (you may experience changes in blood pressure and fits). Tell your doctor or pharmacist before taking the first dose.

Do not take Parnate and talk to your doctor if you have taken any other medicines for the treatment of depression or anxiety within the last 5 weeks and have not discussed this with your doctor. This includes:

  • Selective Serotonin Reuptake Inhibitors (SSRIs), e.g. fluoxetine, paroxetine, sertraline
  • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), e.g. venlafaxine
  • tricyclic antidepressants, e.g. clomipramine, imipramine, amitriptyline, desipramine, dosulepin (dothiepin), nortriptyline, trimipramine or doxepin
  • buspirone hydrochloride

You may experience symptoms of Serotonin Syndrome if Parnate is taken with other anti-depressant drugs (e.g MAOI, SSRIs, SNRIs and tricyclic antidepressants). Symptoms of serotonin syndrome may include confusion, extreme agitation, mood changes, diarrhoea, stiffness, increased body temperature, sweating, changes in blood pressures, nausea, vomiting, involuntary muscle jerk, involuntary shaking or movement in one or more parts of body, difficult movement coordination, disturbances in mental abilities and coma.

You may also experience a condition called neuroleptic malignant syndrome (muscles become stiff and the body no longer moves smoothly), elevated body temperature, fluctuations of vital signs (blood pressure, heart rate and breathing rate) and mental state from extreme agitation progressing to confusion and coma).

Do not take Parnate and talk to your doctor if:

  • you are taking, or being treated with, any of the following:
    - appetite suppressants such as fenfluramine, dexfenfluramine, phentermine (e.g. Duromine), mazindol or diethylpropion for weight loss
    - amphetamines, phenylpropanolamine or other central nervous system stimulants
    - cold or hayfever medicines, including nose drops or sprays
    - dextromethorphan, contained in many cough and cold medicines you can buy without a prescription
    - methyldopa, dopamine, ephedrine or any other medicine that affects blood pressure
    - strong pain killers, e.g. opioid analgesics, codeine, nefopam
    - levodopa (e.g. Madopar or Sinemet) for Parkinson’s disease
    - carbamazepine, used to treat epilepsy, nerve pain, mania or bipolar disease
    - bupropion, used to help stop smoking
    - tryptophan, a dietary supplement to treat depression or anxiety or help you sleep
  • you have or have had any of these medical conditions:
    - a stroke, poor blood flow to the brain, or frequent headaches
    - heart disease or high blood pressure
    - liver disease
    - hyperthyroidism (overactive thyroid gland)
    - blood or bone marrow disorder
    - porphyria, a rare blood pigment disorder
    - phaeochromocytoma, an adrenaline (epinephrine) producing tumour of the adrenal gland
  • you are over 60 years of age.

Do not give Parnate to children and adolescents under 18 years of age. The safety of Parnate in this age group has not been established.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Do not give this medicine to anyone else. Your doctor has prescribed it specifically for you and your condition.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • diabetes
  • epilepsy (condition where you have repeated fits or convulsions)
  • angina (chest pain)
  • kidney problems
  • addiction to drugs or alcohol
  • angle-closure glaucoma (sudden rise in intra-ocular pressure)
  • sugar intolerance.

Tell your doctor as soon as possible if you are planning to have any type of surgery. Parnate may interfere with some medicines used during surgery.

Tell your doctor if you are pregnant or plan to become pregnant. Parnate should not be used in pregnancy unless considered essential by doctor. Your doctor will discuss the risks and benefits of using Parnate if you are pregnant. If you take this medicine during the last three months of your pregnancy, the general condition of your newborn baby might be affected and baby may experience drug withdrawal symptoms such as difficulty in breathing, tiredness, unsettled crying and irritability, changes in blood pressure, fits (convulsions) and involuntary muscle jerk. Increased risk of congenital abnormalities and preterm birth has been observed with the use of this medicine.

Tell your doctor if you are breastfeeding or planning to breastfeed. Your doctor will discuss the risks and benefits involved. It is not recommended that you breastfeed while taking Parnate as it passes into breast milk.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop. Some medicines and Parnate may interfere with each other.

Tell your doctor or pharmacist if you are taking any of the following:

  • any medicine listed under ‘When you must not take it’
  • guanethidine, reserpine or any other medicine that affects blood pressure
  • sedatives, medicines to help you sleep, reduce anxiety or induce anaesthesia
  • anticholinergic medicines, e.g. atropine, which are used to treat a range of medical conditions
  • medicines used to treat Parkinson’s Disease
  • medicines used to treat diabetes
  • medicines used to treat epilepsy
  • anticoagulants, used to treat blood clotting disorders
  • antihistamines, used to treat allergies
  • metrizamide, a contrast medium used in medical imaging.

These medicines may be affected by Parnate or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Parnate.

HOW TO TAKE PARNATE

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The usual dose of Parnate is one 10 mg tablet taken twice a day.

How to take it

Swallow Parnate tablet(s) whole with a full glass of water or another liquid. Do not chew the tablets.

When to take it

Parnate tablets are usually taken in the morning and at midday. Take the last dose of the day not later than 3 pm. This will help avoid sleep disturbances.

How long to take it

For depression, the length of treatment will depend on how quickly your symptoms improve. Most antidepressants take time to work, so do not be discouraged if you do not feel better right away. Some of your symptoms may improve in 1 or 2 weeks, but it can take up to 4 or 6 weeks to feel any real improvement. Even when you feel well, you will usually have to take Parnate for several months or longer. Continue taking Parnate until the doctor tells you to stop.

If you forget to take it

Do not take a double dose to make up for the dose that you missed. Wait until the next dose and take your normal dose then.

Do not try to make up for the dose that you missed by taking more than one dose at a time. This may increase the chance of you getting an unwanted side effect.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone in Australia 13 11 26; telephone in New Zealand 0800 POISON or 0800 764 766) for advice, or go to the Accident and Emergency Department at your nearest hospital, if you think that you or anyone else may have taken too much Parnate.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose commonly include fast heartbeat, sweating, fever, restlessness and excitement. Tremors, depression, stupor or coma may also be present or develop. Blood pressure may increase but it also could drop lower than normal.

WHILE YOU ARE USING PARNATE

Things you must do

If you are about to be started on any new medicine, remind your doctor, pharmacist or dentist that you are taking Parnate or if you were taking it and stopped less than two weeks ago. This applies to medicines that you buy without a prescription as well as prescription medicines.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery or emergency treatment, tell your doctor or dentist that you are taking Parnate or have used it in the last two weeks. It may affect other medicines used during surgery.

Carry an alert card or wear an SOS bracelet, which tells the doctor, dentist or pharmacist you are taking Parnate. These are helpful if you are in an accident and cannot talk.

You must avoid certain foods and drinks during treatment with Parnate and for at least a week after stopping therapy.

Avoid protein foods that have been aged or fermented to improve flavour. Also avoid any foods that have caused you unpleasant reactions previously.

While taking Parnate, you should avoid:

  • matured cheese
  • meat, fish, poultry, pate or yoghurt that is stale or smells “off”
  • protein extracts such as Marmite, Vegemite, Bonox, Bovril, Promite
  • pods of broad beans, sauerkraut
  • smoked or pickled fish
  • sour cream
  • soy bean products, e.g. soy sauce, miso, tofu
  • avocados
  • yeast extracts
  • banana skins
  • red wines such as Chianti
  • home brewed beers or liqueurs.

Parnate reacts with a chemical found in these foods. This reaction may cause sudden high blood pressure which may be experienced as severe headache, stiff or sore neck, nausea, vomiting, fast or slow heartbeat, changes in vision, or sweating with initial paleness then sometimes followed by flushing of the skin.

Avoid large amounts of caffeine-containing foods or drinks such as chocolate, coffee, tea or cola during treatment with Parnate and for at least a week after ceasing therapy. These may trigger off a migraine-like headache in some people taking Parnate.

Things you must not do

Do not take Parnate to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or change the dose without checking with your doctor. Some people may suffer symptoms such as dizziness or anxiety if Parnate is stopped suddenly. If possible, your doctor will gradually reduce the amount you take each day before stopping the medicine completely.

Things to be careful of

Watch carefully for signs that your depression or anxiety is getting worse, especially in the first few weeks of treatment.

Tell your doctor immediately if you experience any of the following symptoms, especially if they are severe, you have not had these symptoms before or they happen very suddenly:

  • anxiety or agitation
  • panic attacks
  • difficulty sleeping
  • hostility or impulsiveness
  • restlessness
  • overactive or uninhibited behaviour
  • thoughts of suicide.

Tell your doctor immediately if you have any thoughts about suicide or doing harm to yourself. All thoughts or talk about suicide or violence are serious. The risk is increased in young adults aged 18 - 24 years. Improvement may not occur during the initial treatment period (usually one to two months).

If you or someone you know is showing the following warning signs, either contact your doctor or a mental health advisor right away or go to the nearest hospital for treatment:

  • thoughts or talk about death or suicide
  • thoughts or talk about self-harm or doing harm to others
  • any recent attempts of self-harm
  • increase in aggressive behaviour, irritability or agitation.

Be careful driving or operating machinery until you know how Parnate affects you. Parnate may cause drowsiness, dizziness or light-headedness in some people. Make sure you know how you react to Parnate before you drive a car or operate machinery.

Be careful when drinking alcohol while you are taking this medicine. If you drink alcohol, drowsiness, dizziness or light-headedness may be worse.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Parnate.

This medicine helps most people with depression, but it may have unwanted side effects in some people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • rash
  • dizziness or blurred vision
  • drowsiness, weakness or fatigue
  • feeling numbness or pins and needles
  • difficulty sleeping
  • chills, tremors
  • nervousness
  • dry mouth
  • nausea, vomiting
  • constipation, diarrhoea
  • stomach pain, loss of appetite
  • ringing in the ears
  • swelling in ankles or limbs
  • excess sweating
  • sexual problems.

Tell your doctor immediately if you notice any of the following:

  • thoughts of suicide
  • severe dizziness or fainting on standing
  • fever
  • unusual bleeding or bruising
  • reduction in some blood cells
  • yellowing of the skin and eyes (jaundice)
  • agitation, confusion or nervousness
  • muscle spasms or twitches
  • difficulty passing urine or unable to empty urine from bladder.

The above list includes serious side effects that may require medical attention.

Stop taking Parnate and contact your doctor or go to the Emergency Department of your nearest hospital if any of the following happens:

  • serious allergic reaction (swelling of the face, lips, mouth or throat which may cause difficulty swallowing or breathing)
  • chest palpitations, fast heartbeat or frequent headaches
  • headache which may start at the back of the head and radiate forward, accompanied by chest pain, palpitations, neck stiffness or soreness, nausea, vomiting, either fast or slow heartbeat, sweating, with initial paleness sometimes followed by flushing of the skin, enlarged pupils and light sensitivity.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Some side effects (for example, changes in liver function or blood) can only be found when your doctor does tests from time to time to check your progress.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

AFTER USING PARNATE

Storage

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep the pack in a cool dry place where the temperature stays at or below 25°C.

Do not store Parnate in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep Parnate where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Parnate or the expiry date has passed, ask your pharmacist what to do with any tablets that are left over.

PRODUCT DESCRIPTION

What it looks like

Parnate tablets are red, round, biconvex film coated tablets. Each Parnate tablet contains 10 mg of tranylcypromine (as sulfate). Parnate comes in packs of 50 tablets.

Ingredients

Parnate contains 10 mg of tranylcypromine as the active ingredient. It also contains:

  • calcium sulfate dihydrate
  • maize starch
  • sucrose
  • magnesium stearate
  • gelatin
  • erythrosine aluminium lake
  • Opadry complete film coating system 06H250000 Red PI (106298)
  • carnauba wax.

Parnate tablets do not contain lactose, gluten or tartrazine.

Sponsor

Distributed in Australia by:

Amdipharm Mercury (Australia) Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

Australian registration number: AUST R 174086

Distributed in New Zealand by:

Boucher & Muir (NZ) Ltd t/a Mercury Pharma (NZ)
39 Anzac Road
Browns Bay
Auckland 0753

This leaflet was revised on 12 December 2022.

Amdipharm Mercury (Australia) Pty Ltd is licensed to use the trademark Parnate.

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Parnate

Active ingredient

Tranylcypromine

Schedule

S4

 

1 Name of Medicine

Tranylcypromine sulfate.

2 Qualitative and Quantitative Composition

Each tablet contains tranylcypromine 10 mg as sulfate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Parnate tablets are 'geranium rose' coloured, biconvex film coated tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Parnate tablets are for oral administration only.

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. 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/day. When a 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 tranquilliser, the dosage of Parnate is not affected. When the medicine 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.

Elderly.

See Section 4.3 Contraindications.

Paediatric population.

Parnate is not indicated for children under 18 years of age.

4.3 Contraindications

Because the effect of many antidepressant medicines may persist for several days, do not commence Parnate therapy within less than the time periods specified below then use half the normal dosage for the first week. Similarly, allow at least a week (or longer as specified below) to elapse between the discontinuance of Parnate and the administration of any other medicine that is contraindicated with Parnate.
Parnate is contraindicated in the following.

In patients with a known hypersensitivity to tranylcypromine or to any of the excipients.


In combination with other MAOIs.

Such as phenelzine and moclobemide, furazolidone, iproniazid, isocarboxazid, nialamide, pargyline and procarbazine hydrochloride. Avoid for at least 2 weeks after stopping previous MAOI and then start at a reduced dose. Similarly, at least a week should elapse between the discontinuance of tranylcypromine and the administration of another MAOI, or the readministration of tranylcypromine. Hypertensive crises or severe convulsive seizures may occur in patients receiving such combinations.

In combination with, or within 3 weeks of, clomipramine or imipramine.

Clomipramine, in combination with a MAOI, has been reported to result in hyperpyrexia, diffuse intravascular coagulation, and status epilepticus.

In combination with other dibenzazepine (tricyclic) antidepressants.

Such as amitriptyline, desipramine, dosulepin (dothiepin), nortriptyline, trimipramine and doxepin or in combination with carbamazepine, as these combinations may induce hypertensive crises or severe convulsive seizures. Reports of hyperactivity, hypertonicity, hyperpyrexia, coma and death have been associated with the use of tranylcypromine in combination with tricyclic antidepressants. Tetracyclic antidepressants should also be avoided. After stopping Parnate, do not start tricyclic related antidepressants for 2 weeks, also MAOIs should not be started until at least 1-2 weeks (3 weeks in case of clomipramine or imipramine) after stopping tricyclic antidepressants.

In combination with sympathomimetics.

Including amphetamines, fenfluramine or similar antiobesity agents, ephedrine, phenylpropanolamine and over the counter (OTC) medicines such as cold, hay fever and weight reducing preparations that contain vasoconstrictors, as severe hypertensive reactions may result. Also methyldopa, dopamine, levodopa and tryptophan as they may result in potentiation, precipitating hypertension, severe headache and hyperpyrexia; cerebral haemorrhage may occur. MAOIs in combination with tryptophan have been reported to cause behavioural and neurologic syndromes including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyper-reflexia, shivering, ocular oscillations and Babinski's signs. Patients must be warned against self medication with proprietary medicines such as cold, hay fever or weight reducing medicines that contain pressor agents.

With pethidine, closely related narcotic analgesics and nefopam.

As CNS excitation or depression, respiratory depression, hypotension, or hypertension, restlessness and coma may ensue. Wait until two weeks after stopping MAOIs before starting treatment with opioid analgesics.

In combination with dextromethorphan.

The combination of MAOIs and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behaviour.

In combination with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

There have been reports of serious and sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation leading to delirium and coma) in patients receiving fluoxetine in combination with MAOIs and in patients who have recently discontinued fluoxetine prior to the commencement of MAOI therapy. There also have been cases presented with features resembling neuroleptic malignant syndrome. Use of MAOIs with or after fluvoxamine has been reported to produce a serotonin syndrome, sometimes fatal.
Therefore, Parnate should not be used in combination with fluoxetine, or its congeners. Allow at least five weeks between discontinuation of fluoxetine and initiation with Parnate, as fluoxetine and its major metabolite have very long half-lives. 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).

In combination with bupropion.

The concurrent administration of bupropion and a MAOI is contraindicated. At least two weeks should elapse between discontinuation of a MAOI and initiation of treatment with bupropion.

In combination with buspirone hydrochloride.

Parnate should not be used in combination with buspirone hydrochloride since several cases of elevated blood pressure have been reported in patients taking MAOIs who were then given buspirone hydrochloride. At least 10 days should elapse between the discontinuation of Parnate and the institution of buspirone HCl.

In combination with cheese or other foods with a high tyramine content.

Hypertensive crises have sometimes occurred during Parnate therapy after ingestion of foods with a high tyramine content. It is therefore important that patients be told to avoid matured cheese and protein extracts such as Marmite, Vegemite, Bonox, Bovril, etc. In general, the patient should avoid protein foods in which ageing or protein breakdown is used to increase flavour. Other foods to be avoided are the pods of broad beans (which contain levodopa), sauerkraut, pickled herring, sour cream, soy sauce, avocado pears, yeast extracts and banana skins. Alcoholic drinks, which may contain significant amounts of tyramine, especially red wine such as Chianti, should also be avoided.

In patients with cerebrovascular or cardiovascular disease, a history of recurrent or frequent headaches, blood dyscrasias or porphyria.

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 patients with known blood dyscrasia or porphyria.

In patients with phaeochromocytoma.

Parnate should not be used in the presence of phaeochromocytoma, or if it is suspected, as such tumours secrete pressor substances.

In patients with hyperthyroidism.

These patients have increased sensitivity to pressor amines.

In the elderly.

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.

In patients with impaired hepatic function.

Parnate should not be used in patients with a history of liver disease or in those with abnormal liver function tests.

4.4 Special Warnings and Precautions for Use

Like all powerful medicines Parnate may occasionally provoke serious adverse effects. If patients are kept under regular and frequent observation, the medicine can be stopped should any adverse effect occur. It is important for the physician to be fully aware of the adverse effects, contraindications and precautions described in the prescribing information.

Clinical worsening and suicide risk.

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 (suicidality) whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
The risk is increased in patients less than 25 years old. As improvement may not occur during the first few weeks or more of treatment, 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. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistent or whose emergent suicidality is severe, abrupt in onset or was not part of the patient's presenting symptoms.
Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation/ behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Patients with comorbid depression associated with other psychiatric disorders being treated with antidepressants should be similarly observed for clinical worsening and suicidality.
Pooled analyses of 24 short-term (4-16 weeks), placebo controlled trials of nine antidepressant medicines (SSRIs and others) in 4,400 children and adolescents with major depressive disorders (16 trials), obsessive compulsive disorder (4 trials), or other psychiatric disorders (4 trials) have revealed a greater risk of adverse events representing suicidal behaviour or thinking (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients treated with an antidepressant was 4%, compared with 2% of patients given placebo. There was considerable variation in risk among the antidepressants but there was a tendency towards an increase for almost all antidepressants studied. The risk of suicidality was most consistently observed in the major depressive disorder trials, but there were signals of risk arising from trials in other psychiatric indications (obsessive compulsive disorders and social anxiety disorder) as well. No suicides occurred in these trials. It is unknown whether the suicidality risk in children and adolescent patients extends to use beyond several months. The nine antidepressant medicines in the pooled analyses included five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRIs (bupropion, mirtazapine, nefazodone, venlafaxine).
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond the age of 24 years, and there was a reduction with antidepressants compared to placebo in adults aged 65 years and older.
Symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania and mania, have been reported in adults, adolescents and children being treated with antidepressants for major depressive disorders as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, there is concern that such symptoms may be precursors of emerging suicidality.
Families and caregivers of patients being treated with antidepressants for major depressive disorders or for any other condition (psychiatric or nonpsychiatric) should be informed about the need to monitor these patients for the emergence of agitation, irritability, unusual changes in behaviour and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
Prescriptions for Parnate should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Mania and bipolar disorder.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with any antidepressant alone may increase the likelihood of a mixed/ manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder. It should be noted that tranylcypromine is not approved for use in treating bipolar depression.
Caution is required when giving Parnate in the following conditions.

Diabetes.

Some MAOIs 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.

Epileptic patients.

Because the influence of tranylcypromine on the convulsive threshold is variable in animal experiments, suitable precautions should be taken if epileptic patients are treated with Parnate.

Surgery.

Although excretion of tranylcypromine is rapid, it is advisable wherever possible to discontinue Parnate therapy at least two weeks before surgery because of possible interference with the action of certain anaesthetics and analgesics. Patients taking MAOIs should not be given cocaine or local anaesthesia containing vasoconstrictors. The possible combined hypotensive effects of MAOIs and spinal anaesthesia should be kept in mind.

Patients with angina.

MAOIs have the capacity to suppress anginal pain that would otherwise serve as a warning of myocardial ischaemia.

Patients with a history of drug or alcohol dependence.


Angle-closure glaucoma.

Antidepressants including PARNATE may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in pre-disposed patients. PARNATE should therefore be used with caution in patients with raised intraocular pressure and in those at risk of angle-closure glaucoma.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.

Parnate contains sucrose. Patients with these conditions should not take this medicine.

Stopping treatment.

Parnate therapy should be withdrawn gradually to reduce the risk of withdrawal symptoms (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in renal impairment.

There is a possibility of cumulative effects in patients with impaired renal function.

Use in hepatic impairment.

See Section 4.3 Contraindications.

Use in the elderly.

See Section 4.3 Contraindications.

Paediatric use.

The safety and efficacy of Parnate for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Parnate should not be used in this age group for the treatment of depression or other psychiatric disorders.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients should be specifically asked if they are taking any other medication because of the possibility of drug interactions.
See Section 4.3 Contraindications for medicines that should not be taken with Parnate.
Exercise caution when giving Parnate with the following medicines.

Guanethidine.

As its action may be antagonised.

Reserpine.

As hyperactivity may occur.

Other hypotensive agents.

Because of the possibility of additive hypotensive effects.

Barbiturates and possibly other hypnotics, and antimuscarinic agents.

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.

Anticoagulants.

As some animal studies have suggested that the effect of anticoagulants may be potentiated if a MAOI is given concurrently. One suspected case of potentiation has been reported in man.

Oral hypoglycaemic agents or insulin.

As their action may be potentiated.

Metrizamide.

Should be avoided since it may lower the seizure threshold.

Antiepileptics.

Since MAOIs possibly antagonise anticonvulsant effects of antiepileptics (convulsive threshold lowered).

Antihistamines.

Since antimuscarinic and sedative effects of antihistamines are increased by MAOIs.
Patients should be advised not to consume excessive amounts of caffeine in any form. See Section 4.3 Contraindications, for other foods and drinks to avoid while taking Parnate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
Adequate human data on use during pregnancy and adequate animal reproduction data are not available. Parnate should not be used in pregnancy unless considered essential by the physician.
Use of any medicine in pregnancy requires that the potential benefits of the medicine be weighed against its possible hazards to mother and child. Animal reproductive studies show that tranylcypromine passes through the placental barrier into the foetus of the rat.
Epidemiological studies have suggested an increased risk of congenital abnormalities associated with use of antidepressants in pregnancy.
Neonates exposed to antidepressants late in the third trimester have shown drug withdrawal symptoms such as dyspnoea, lethargy, colic irritability, hypotension or hypertension and tremor or spasms.
Epidemiological data suggests that the use of antidepressants in pregnancy may be associated with an increase in preterm delivery.
Adequate human data on use during lactation and adequate animal reproduction data are not available. Tranylcypromine is secreted into breast milk of lactating mothers but the clinical significance of this has not been fully evaluated.
Therefore, Parnate should be used in lactating women only if clearly needed and if the potential benefits justify the potential risk.

4.7 Effects on Ability to Drive and Use Machines

Parnate may affect the ability to drive or operate machinery.
Tranylcypromine may cause dizziness and drowsiness. Patients should be advised not to drive a vehicle or operate machinery if they are affected. Avoid alcohol, see Section 4.3 Contraindications.

4.8 Adverse Effects (Undesirable Effects)

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. These crises are characterised by some or all of the following symptoms: occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, multiple extrasystoles, often with substernal pain, nausea or vomiting, sweating with early pallor, sometimes followed later by flushing. Either tachycardia or bradycardia may be present and associated mydriasis, angle-closure glaucoma and photophobia may also occur. Throbbing headache may be an early warning of hypertensive crisis. This headache, together with pain and stiffness in the cervical muscles, may mimic subarachnoid haemorrhage, 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.
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.). 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.

Other side effects.

The most frequently seen side effect is insomnia, which can usually be overcome by giving the last dose of the day not later than 3 pm, by reducing the dose or by prescribing a mild hypnotic. Occasional cases of dizziness, palpitation, weakness, fatigue, dry mouth and drowsiness have been reported, as have nausea, vomiting, diarrhoea, abdominal pain and constipation, sleep disturbances and skin rash. Most of these effects can be relieved by lowering the dosage or by giving suitable concomitant medication.
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, the medicine should be discontinued.
Hypotension, which may be postural, has been observed during Parnate therapy. Syncope has been rarely seen. Dosage should not be increased in the presence of hypotension. This adverse effect is usually temporary, but if it persists, the medicine should be discontinued. The blood pressure will then return rapidly to pretreatment level.
Tachycardia, significant anorexia, oedema, blurred vision, chills and impotence have each been reported.
Impaired water excretion compatible with the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) has been reported.
Overstimulation (which may include increased anxiety and agitation) and manic symptoms may sometimes occur with normal dosage but is more commonly associated with overdosage. Reduction of the dose is indicated. In certain instances it may be helpful to administer a sedative phenothiazine tranquilliser, such as chlorpromazine, concomitantly.
There is a risk of dependency development, with tolerance to high doses, which can occur in patients without past history of drug dependence. This should be distinguished from the return of features of the original illness on cessation of treatment. Withdrawal symptoms may be anticipated.
Rare instances of hepatitis, hepatocellular damage, jaundice, hallucinations and blood dyscrasias have been reported.
Tinnitus, muscle spasm, tremors, myoclonic jerks, numbness, paraesthesia, urinary retention and retarded ejaculation have been reported.
Haematological disorders including anaemia, leukopenia, agranulocytosis and thrombocytopenia have been reported.
Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

The characteristic symptoms that may be caused by overdosage are usually those described, see Section 4.8 Adverse Effects (Undesirable Effects). Tachycardia, sweating and hyperpyrexia with restlessness and excitement are usually produced. Tremor, convulsions, depression, stupor or coma may, however, be present or develop. Blood pressure may be raised, but hypotension may supervene.

Treatment.

Treatment should normally consist of general supportive measures, close observation of vital signs and steps to counteract specific symptoms as they occur since MAO inhibition may persist. The management of hypertensive reactions is described, see Section 4.8 Adverse Effects (Undesirable Effects).
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. Metaraminol may be required if marked refractory hypotension occurs (left ventricular failure should be excluded).
A successful recovery following haemodialysis after a self-administered overdosage of 350 mg of tranylcypromine has been reported.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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. When tranylcypromine is withdrawn, monoamine oxidase activity is recovered in 3 to 5 days, although the drug is excreted in 24 hours.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Carcinogenicity.

No data available.

Genotoxicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Parnate tablets contains calcium sulfate dihydrate, maize starch, sucrose, erythrosine aluminium lake, magnesium stearate, gelatin, opadry complete film coating system 06H250000 Red PI (106298) and carnauba wax.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

PVC-PVDC/Aluminium blister packs of 50 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Name: (1RS,2SR)-2-phenyl-cyclopropylamine sulfate.
Molecular formula: (C9H11N)2,H2SO4. Molecular weight: 364.5.
Tranylcypromine sulfate is a white or almost white, crystalline powder, soluble in water, very slightly soluble in ethanol (96%) and in ether.

CAS number.

13492-01-8.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes