Consumer medicine information

Nardil Tablets

Phenelzine

BRAND INFORMATION

Brand name

Nardil Tablets

Active ingredient

Phenelzine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Nardil Tablets.

What is in this leaflet

Please read this leaflet carefully before you take Nardil.

This leaflet answers some common questions about Nardil. 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 Nardil 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 Nardil is used for

The name of your medicine is Nardil. It contains the active ingredient phenelzine.

Nardil is used to treat major depression. There are many different types of medicines used to treat depression. Nardil belongs to a group of medicines called Monoamine Oxidase Inhibitors (MAOIs).

Depression is longer lasting and/or more severe than the "low moods" everyone has from time to time due to the stress of everyday life. It is thought to be caused by a chemical imbalance in parts of the brain. This imbalance affects your whole body and can cause emotional and physical symptoms such as feeling low in spirit, loss of interest in activities, being unable to enjoy life, poor appetite or overeating, disturbed sleep, often waking up early, loss of sex drive, lack of energy and feeling guilty over nothing.

Antidepressants are thought to work by acting on brain chemicals called amines, which are involved in controlling mood.

Your doctor, however, may prescribe Nardil for another purpose.

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

This medicine is available only with a doctor's prescription.

Before you take Nardil

When you must not take it

Do not take Nardil if:

  • You have an allergy to phenelzine, or any of the ingredients listed at the end of this leaflet.
    Allergic symptoms may include difficulty breathing, closing of your throat, swelling of your lips, tongue or face; hives, headaches, dizziness, drowsiness, tremors, weakness, or muscle twitches.
  • If you are taking guanethidine (a medicine for controlling blood pressure)
  • If you have heart disease or heart failure.
  • You have a disease affecting blood flow to your brain, such as stroke.
  • You have a growth on the adrenal glands near your kidneys which is causing high blood pressure (phaeochromocytoma)
  • You are planning to undergo elective surgery requiring general anaesthesia, cocaine or certain local anaesthesia.
  • You have a history of liver disease or abnormal liver function tests.
  • You are in the manic phase of bipolar disorder.
  • You are currently taking other antidepressants or have taken other antidepressants within the last ten days.
    Taking Nardil with other antidepressants may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions.

Ask your doctor or pharmacist if you are not sure if you have been taking one of these medicines.

Do not give Nardil to children and adolescents under 18 years of age.

The safety of Nardil in this age group has not been established.

Do not take Nardil after the expiry date (EXP) printed on the pack.

It may have no effect at all, or an entirely unexpected effect if you take it after the expiry date.

Do not take Nardil if the packaging is torn or shows signs of tampering, or if the tablets do not look quite right.

If you are not sure whether you should start taking Nardil, contact your doctor.

Before you start to take it:

You must tell your doctor if:

  • You are allergic to any other medicines, foods, dyes, or preservatives.
  • You have or have had any other health problems including:
    - Heart disease
    - Tumours of the adrenal gland
    - Diabetes
    - Epilepsy
    - Liver disease

You are pregnant or are intending to become pregnant.

Your doctor will discuss the risks and benefits of using Nardil when pregnant.

You are breastfeeding or wish to breastfeed.

Your doctor will discuss the risks and benefits of using Nardil when breastfeeding.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Nardil.

How to take Nardil

Use Nardil exactly as your doctor has prescribed.

The directions from your doctor may differ from the information contained in this leaflet.

How much to take

The usual starting oral dose of Nardil is one tablet (15 mg) three times a day. Your dose may vary depending on your medical condition.

Your doctor will instruct you on how much Nardil to take each day and how long to take it.

Follow all directions given to you by your doctor and pharmacist carefully.

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

How to take it

Swallow Nardil with a glass of water.

How long to take it

Most antidepressants take time to work, so do not be discouraged if you do not feel better straight away. It may take up to four weeks to feel the full benefit of Nardil. You may need to take Nardil for several months or longer.

Do not stop taking Nardil unless instructed by your doctor.

If you forget to take it.

Do not take an extra dose. Wait until the next dose and take your normal dose then.

Do not try to make up for the dose you have missed by taking more than one dose at a time.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

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

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention. Keep telephone numbers for these places handy.

If you take too much Nardil you may feel: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, spasm of jaw resulting in reduced opening of the jaw, rigidity, whole body spasms and body arching, convulsions and coma, rapid and irregular pulse, high blood pressure, low blood pressure and vascular collapse, chest pain, breathing difficulties and failure, fever, excessive sweating, and cool, clammy skin.

If you are not sure what to do, contact your doctor or pharmacist.

While you are using Nardil

Things you must do

Before you have any surgery or emergency treatment, tell your doctor or dentist that you are taking Nardil or have used it within the last ten days. Carry an alert card or wear an SOS bracelet which tells the doctor you are taking Nardil.

These are helpful if you are in an accident and cannot talk.

If you are about to be started on any new medicines, tell your doctor or pharmacist that you are taking Nardil.

Do not take any other medicines, whether they require a prescription or not, without first telling your doctor.

Tell your doctor if you become pregnant while taking Nardil.

Talk to your doctor about what foods you should avoid.

Nardil reacts with alcohol and certain foods and drinks that contain the chemical Tyramine.

The following foods and beverages may react with Nardil:

Meat and fish:

  • Pickled herring
  • Liver
  • Dry sausage (including salami, peperoni)

Vegetables:

  • Broad bean pods
  • Sauerkraut

Dairy products:

  • Cheese (cottage cheese and cream cheese are allowed)
  • Avoid items made from cheese eg. spreads, pizza, mornay sauce
  • Yoghurt

Beverages:

  • Beer
  • Red wine
  • Alcohol-free and reduced alcohol beer and wine products (white wine, spirits and commercial beers are allowed, however see warning under “Things to be careful of”).

Miscellaneous:-

  • Yeast extract (including brewer's yeast in large quantities and yeast spreads such as Vegemite and Marmite)
  • Meat extract (e.g. Bovril, meat stock cubes, packet soup)
  • Excessive amounts of caffeine and chocolate
  • Any spoiled or improperly refrigerated, handled or stored protein-rich foods such as meats, fish and dairy products
  • Soy sauce
  • Foods that may have undergone protein changes by ageing, pickling, fermentation or smoking to improve flavour.

The above list of foods and beverages should be avoided while taking Nardil, and for two weeks after discontinuing Nardil therapy.

Consuming foods and beverages outlined in this list may cause a severe in increase in blood pressure. Symptoms include a headache, rapid heart beat, nausea or vomiting.

If you have a reaction after consuming one of these foods or beverages, call your doctor or go to Accident and Emergency at your nearest hospital.

If you took a small amount of one of these foods one time, without a reaction, it does not mean you will not have a reaction the next time.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Otherwise, your doctor may think that your currently prescribed dose is not working as expected and change your treatment unnecessarily.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Your doctor may want to take some blood tests and check your heart and blood pressure from time to time. This helps prevent unwanted side effects.

If you are taking Nardil, you should report the occurrence of headaches or other unusual symptoms.

Things you must not do

Do not stop taking Nardil or lower the dose, without first checking with your doctor.

Do not let yourself run out of medicine over the weekend or on holidays.

Suddenly stopping Nardil has been shown on rare occasions to cause nightmares, restlessness, convulsions or abnormal thoughts.

Do not give this medicine to somebody else, even if their symptoms seem similar to yours or if they have the same condition as you.

Do not use Nardil to treat other complaints unless your doctor says to.

Things to be careful of

Watch carefully for signs that your depression or anxiety is getting worse, especially in the first one to two months of treatment or when there is a change in dose.

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
  • Overactivity or uninhibited behaviour
  • Thoughts of suicide

Tell your doctor immediately if you have any thoughts about suicide or doing harm to yourself.

Warning signs of suicide:
All thoughts or talk about suicide or violence are serious. The risk is increased in young adults aged 18-24 years during the initial treatment period (usually one to two months) and at the time of dose changes.

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
  • An increase in aggressive behaviour, irritability or agitation.

Warnings for use in pregnancy:
You must tell your doctor if you are pregnant or are intending to become pregnant.

There have been reports of some congenital abnormalities or an increase in pre-term delivery associated with taking antidepressants in pregnancy.

Some infants exposed to antidepressants late in the third trimester have shown drug withdrawal symptoms such as difficulty breathing, sluggish, colic irritability, low or high blood pressure, and tremor or spasms.

Your doctor will discuss the possible risks and benefits of taking Nardil during pregnancy.

There are certain prescription and over the counter medications that should not be taken when you are taking Nardil.

The medications to avoid:

  • Cold and cough preparations (including those containing dextromethorphan)
  • Nasal decongestants (tablets, drops or spray)
  • Hay-fever medications
  • Sinus medications
  • Asthma inhalant medications
  • Anti-appetite medicines
  • Weight-reducing preparations
  • "Pep" pills
  • Tryptophan, tyrosine and phenylalanine-containing preparations

Tell your doctor if you are taking any of the following medications before starting Nardil:

  • Other antidepressants
  • Medication for high blood pressure and/or heart rate (anti-hypertensives or beta-blockers)
  • Fluid tablets (diuretics)

If you are under the care of another physician or dentist, you should inform him/her that you are taking Nardil.

Be careful driving or operating machinery until you know how Nardil affects you.

Nardil may cause drowsiness or sleepiness in some people, and affect alertness. Make sure you know how you react to Nardil before you drive a car or operate machinery, or do anything else that could be dangerous if you are drowsy, dizzy or not alert.

Avoid alcohol while taking Nardil.

Alcohol interacts with Nardil. Alcohol may also make you more sleepy, dizzy and light headed than usual.

Avoid large amounts of caffeine-containing foods or drinks such as chocolate, coffee, tea or cola.

This may trigger a migraine-like reaction in some people taking Nardil.

You should wait at least ten days after stopping Nardil before starting another antidepressant from the MAOI group.

Older people may be more sensitive to Nardil. Families and carers should be aware of this. Special care may be needed.

Side Effects

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

Nardil 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 treatment if you get some of the side effects.

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

  • Dizziness
  • Dizziness on standing
  • Drowsiness and excessive sleeping
  • Headache
  • Difficulty sleeping
  • Blurred vision
  • Fatigue
  • Weakness
  • Constipation
  • Dry mouth
  • Nausea or feeling sick
  • Vomiting
  • Involuntary movements including tremors, twitching, muscle spasms and enhanced reflexes
  • Sexual disturbances (difficulty in achieving an orgasm or ejaculating)
  • Fluid retention/swollen ankles
  • Weight gain
  • Changes in the blood related to liver problems which may be detected in a blood test

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • Unsteady walking
  • Severe mental confusion and lethargy, coma
  • Disordered thinking
  • Excitability and mental instability
  • Mistaken belief of being infested by parasites
  • Fits
  • Severe anxiety
  • Episodes of delusions and hallucinations
  • Uncontrollable muscle contractions
  • Tingling and/or numbness of the hands or feet
  • Involuntary inability to speak
  • Slowing of the heart rate and breathing following electroconvulsive therapy (ECT)
  • Neuroleptic malignant syndrome. Symptoms include high fever, sweating, unstable blood pressure, reduced consciousness, muscle stiffness and reduced automatic bodily functions.
  • Signs of liver damage, such as yellow skin/eyes
  • Abnormality of the blood cells causing bleeding problems, weakness, pale skin colour or frequent infections
  • A disease affecting the immune system with flu-like symptoms and/or rash
  • An increase in water and a decrease in salt in the blood which may cause drowsiness, confusion or fits
  • Increased metabolism
  • Swollen glottis which is at the top of the wind pipe
  • High temperature with muscle stiffness

These are all serious side effects. You may need urgent medical attention. These side effects are very rare.

If any of the following happen, stop taking Nardil and tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

  • Headache at the back of the head which spreads to the front
  • Irregular heart beat
  • Neck stiffness or soreness
  • Sick feeling
  • Vomiting
  • Sweating with high temperature
  • Enlarged pupils and sensitivity to light
  • Increased or decreased heart rate
  • Chest pain

These are all very serious side effects involving blood pressure changes. You may need urgent medical attention or hospitalisation.

All of these side effects are very rare.

Remember that a number of foods and drinks including alcohol may react with Nardil. Your doctor and your pharmacist will tell you which foods may trigger adverse events with Nardil.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Check with your doctor as soon as possible if you have any problems while taking Nardil even if you do not think the problems are connected with Nardil or are not listed in this leaflet.

Ask your doctor or pharmacist if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Nardil

Storage

Keep Nardil where children cannot reach it.

Store between 2°C to 8°C in a refrigerator, unless unavoidable for short periods.

Heat and dampness can destroy some medicines.

Keep your tablets in their container until it is time to take them.

If you take the tablets out of the container, they may not keep as well.

Disposal

If your doctor tells you to stop Nardil, or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets left over.

Product Description

What it looks like

Tablets (orange)

Ingredients

Active ingredient:
15 mg phenelzine (as phenelzine sulfate)

Inactive ingredients:
Mannitol, povidone, maize starch, magnesium stearate, coating (Opadry 20A25096 Red)

Nardil does not contain gluten, lactose, tartrazine or any other azo dyes.

Supplier

Nardil is supplied in Australia by:

Link Medical Products Pty Ltd
5 Apollo Street,
Warriewood NSW 2102
Australia

Nardil is supplied in New Zealand by:

Link Pharmaceuticals Ltd
Level 31, Vero Centre
48 Shortland Street
Auckland, 1140
New Zealand

Australian Registration Number:

Nardil - AUST R 93600

This leaflet was prepared in December 2015.

BRAND INFORMATION

Brand name

Nardil Tablets

Active ingredient

Phenelzine

Schedule

S4

 

Name of the medicine

Phenelzine sulfate.

Excipients.

Mannitol, povidone, starch-maize, magnesium stearate, and Opadry 20A25096 Red.

Description

Molecular Weight: 234.27. Chemical formula: C8H12N2.H2SO4. CAS Number: 156-51-4.
Phenelzine sulfate is a potent inhibitor of monoamine oxidase (MAO). Phenelzine sulfate is a hydrazine derivative.
Each film coated phenelzine sulfate tablet contains phenelzine sulfate equivalent to 15 mg phenelzine base. Inactive ingredients include mannitol, povidone, starch-maize, magnesium stearate, and Opadry 20A25096 Red.

Pharmacology

MAO is a complex flavin containing enzyme system that is widely distributed throughout the body. MAO inhibitors exert their effects mainly on organ systems influenced by sympathomimetic amines and 5-hydroxytryptamine and inhibit not only MAO but also other enzymes as well, interfering with the hepatic metabolism of many drugs. It is unknown whether all the clinical effects produced by this class of drug result from MAO inhibition, other pharmacological actions, or an interaction of both. Therefore the physician should become familiar with all the effects produced by drugs of this class.
Phenelzine sulfate is oxidised by MAO to form reactive intermediates which then irreversibly inactivate the flavin prosthetic group of MAO. In the clinical setting, maximal inhibition of MAO is usually achieved within a few days (5 to 10 days in biopsy samples), although the antidepressant effect may be delayed for 2 to 3 weeks. Evaluation of MAO activity in human subjects indicates that favourable clinical responses are likely to occur when platelet MAO is inhibited by 85%.
Up to 2 weeks may be required to restore amine metabolism to normal following withdrawal of MAO inhibitors, presumably because of the necessity for the resynthesis of MAO. This is the reason why a period of 10 to 14 days is necessary after discontinuing MAO therapy before commencing a normal diet (see Precautions).

Pharmacokinetics.

There is little information available on the pharmacokinetics of phenelzine sulfate. Orally administered phenelzine sulfate is rapidly absorbed from the gastrointestinal tract and has a short half-life reported to be 1.2 hours in humans. The decay in the action-time curve for MAO inhibitors is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of MAO in the tissue compartments where it has been irreversibly inactivated. Although the biological activity of phenelzine sulfate is prolonged due to the characteristics of their interaction with the enzyme, its clinical efficacy appears to be reduced when given less frequently than once daily. Phenelzine sulfate is metabolised primarily by acetylation. The rate of metabolism is dependent upon the kinetic profile of the patient who may be a "slow" or "rapid" acetylator. There has been no consistent correlation noted between acetylator status and adverse effects of the drug. The major metabolites of phenelzine sulfate are phenylacetic acid and parahydroxyphenyl acetic acid. These metabolites constitute up to 79% of a single administered phenelzine dose excreted in the urine within 96 hours. It is not known whether these metabolites have clinical activity.

Indications

For the treatment of major depression.
Phenelzine sulfate should rarely be the first antidepressant drug used. Rather it is more suitable for use with patients who have failed to respond to the drugs more commonly used for these conditions.

Contraindications

Phenelzine sulfate should not be used in patients who are hypersensitive to phenelzine sulfate or any of the ingredients listed in the description, with phaeochromocytoma, cerebrovascular disease, congestive heart failure, a history of liver disease, or with abnormal liver function tests.
MAO inhibitors including phenelzine sulfate are contraindicated in patients receiving guanethidine.
Patients taking phenelzine sulfate should not undergo elective surgery requiring general anaesthesia. Also, they should not be given cocaine or local anaesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of phenelzine sulfate and spinal anaesthesia should be kept in mind. Phenelzine sulfate should be discontinued at least 10 days prior to elective surgery.
Phenelzine sulfate should not be used in combination with selective serotonin reuptake inhibitors (SSRIs) serotonin-noradrenaline reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs) [see Interactions with Other Medicines].
Phenelzine is not indicated in the manic phase.

Precautions

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 young adults aged 18-24 years, during the initial treatment period (usually one to two months) 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 4400 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, there was a reduction with antidepressants compared to the 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.

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.
Families and caregivers of children and adolescents 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 health care 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.
Prescription for Nardil should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

General.

In depressed patients, the possibility of suicide should always be considered and adequate precautions taken. It is recommended that careful observation of patients undergoing phenelzine sulfate treatment be maintained until control of depression is achieved. If necessary, additional measures (ECT, hospitalisation, etc.) should be instituted.
Caution should be exercised if the patient undergoes concurrent electroconvulsive therapy (ECT).
All patients undergoing treatment with phenelzine sulfate should be closely followed for symptoms of postural hypotension. Hypotensive side effects have occurred in hypertensive as well as normotensive and hypotensive patients. Blood pressure usually returns to pretreatment levels rapidly when the drug is discontinued or the dosage is reduced.
Because the effect of phenelzine sulfate on the convulsive threshold may be variable, adequate precautions should be taken when treating epileptic patients.
Phenelzine sulfate may cause excessive stimulation in schizophrenic patients; in manic depressive states it may result in a swing from a depressive to a manic phase.
Phenelzine sulfate should be used with caution in combination with antihypertensive drugs, including thiazide diuretics and β-blockers, since exaggerated hypotensive effects may result.
There is conflicting evidence as to whether or not MAO inhibitors affect glucose metabolism or potentiate hypoglycaemic agents. This should be kept in mind if phenelzine sulfate is administered to diabetics.

Effects on fertility.

25 female white mice were given 25 mg/kg per day phenelzine sulfate by s.c. injection on days 1-6 of pregnancy. The first day of pregnancy was dated from the finding of the vaginal plug. 9 out of 25 (36%) mice had surviving litters at autopsy on day 14, the remaining sixteen showed no signs of implantation. Within the control group, 67% of mice with vaginal plugs became pregnant. This result was statistically significant (p < 0.001). It was concluded that, during the first 6 days of gestation, implantation was partially suppressed.

Use in pregnancy.

(Category B3)
The safe use of phenelzine sulfate during pregnancy has not been established. There are insufficient adequate and well controlled studies in pregnant women. Therefore, phenelzine should be used in pregnant women only if clearly needed and if the potential benefits justify the potential risk to the foetus.
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 suggest that the use of antidepressants in pregnancy may be associated with an increase in preterm delivery.

Use in lactation.

The safe use of phenelzine sulfate during lactation has not been established. There are insufficient adequate and well controlled studies in lactating women. Therefore, phenelzine sulfate should be used in lactating women only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants to phenelzine sulfate, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother, or to discontinue nursing.

Use in children and adolescents (< 18 years).

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

Use in the elderly.

As for adults.
Postural hypotension may be an unwanted effect of MAOIs in the elderly. Elderly patients as a group tend to receive multiple drug therapies and the possibility of increased risk of drug interactions should be borne in mind. Nardil should only be used with great caution in elderly patients.

Carcinogenicity, mutagenicity.

Carcinogenicity has been observed in mouse studies but not in the rat. This is consistent with tumour and mutagenicity data reported for the MAO inhibitor, isoniazid.
A group of 50 male and 50 female random bred Swiss mice, 6 weeks of age, were given 0.015% phenelzine sulfate in the drinking water for their lifetime. An untreated group of 200 mice served as controls. Of the treated group, pulmonary tumours developed as follows: 38% adenomas, 7% adenomas and adenocarcinomas, and 1% adenocarcinomas. This compared to the pulmonary tumour incidence in the untreated group of 14% adenomas, 3% adenomas and adenocarcinomas, and 5% adenocarcinomas. Of the mice in the treated group 26% developed vascular tumours compared to 5% in the untreated group.
An 87 week study of 26 male Sprague-Dawley rats fed diets of phenelzine to evaluate carcinogenesis reported no significant difference in the incidence of both colonic and small intestinal adenocarcinomas between the phenelzine treated group (n = 13) and matched controls (n = 13).
In the Salmonella typhimurium DNA reversion (Ames) test, phenelzine sulfate was a weak inducer of base pair mutations in the absence of metabolic activation by rat liver homogenate. Results obtained in the pol A+/A- DNA reversion test in Escherichia coli report phenelzine sulfate as reactive against DNA. Similarly, phenelzine sulfate has been reported to inactivate Bacillus subtilis plasmid DNA.
There is insufficient evidence to assess the carcinogenicity of phenelzine sulfate in humans.

Warning to the patient.

All patients should be warned that the following foods, beverages and medications must be avoided while taking phenelzine sulfate, and for two weeks after discontinuing use.

Foods and beverages to avoid.

Meat and fish.

Pickled herring, liver, dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna).

Vegetables.

Broad bean pods (fava bean pods) and sauerkraut.

Dairy products.

Cheese, yoghurt (cottage cheese and cream cheese are allowed).

Beverages.

Beer, wine, alcohol free and reduced alcohol beer and wine products.

Miscellaneous.

Yeast extract (including brewer's yeast in large quantities); meat extract; excessive amounts of caffeine and chocolate; any spoiled or improperly refrigerated, handled or stored protein rich foods such as meats, fish and dairy products, including foods that may have undergone protein changes by aging, pickling, fermentation, or smoking to improve flavour.

Medications to avoid.

Cold and cough preparations (including those containing dextromethorphan); nasal decongestants (tablets, drops or spray); hay-fever medications; sinus medications; asthma inhalant medications; anti-appetite medicines; weight-reducing preparations; "pep" pills; tryptophan-containing preparations; selective serotonin reuptake inhibitors (SSRIs); serotonin-noradrenaline reuptake inhibitors (SNRIs); tricyclic antidepressants (TCAs).
Certain prescription drugs should be avoided. Therefore, patients under the care of another physician or dentist should inform him/her that they are taking phenelzine sulfate.
Patients should be warned that the use of the above foods, beverages, or medications may cause a reaction characterised by headache and other serious symptoms due to a rise in blood pressure, with the exception of dextromethorphan which may cause reactions similar to those seen with pethidine.
Patients should be instructed to report promptly the occurrence of headache or other unusual symptoms.
Development of serotonin syndrome may occur in association with treatment with MAOIs particularly when given in combination with SSRIs and SNRIs, or other serotonergic agents. Symptoms and signs of serotonin syndrome include rapid onset of neuromuscular excitation (hyper-reflexia, incoordination, myoclonus, tremor), altered mental status (confusion, agitation, hypomania) and autonomic dysfunction (diaphoresis, diarrhoea, fever, shivering and rapidly fluctuating vital signs). Treatment with phenelzine sulfate should be discontinued if such events occur and supportive symptomatic treatment initiated.

Interactions

The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see Adverse Effects). Therefore, patients being treated with phenelzine sulfate should not take sympathomimetic drugs (including amphetamines, cocaine, methylphenidate hydrochloride, dopamine, adrenaline, noradrenaline and ephedrine) or related compounds (including methyldopa, levodopa, tryptophan, L-tyrosine and phenylalanine). Hypertensive crises during phenelzine sulfate therapy may also be caused by the ingestion of foods with a high concentration of tyramine or dopamine. Therefore, patients being treated with phenelzine sulfate should avoid high protein food that has undergone protein breakdown by aging, fermentation, pickling, smoking or bacterial contamination. Patients should avoid cheeses (especially aged varieties), pickled herring, beer, wine, liver, yeast extract (including brewer's yeast in large quantities), dry sausage (including Genoa salami, hard salami, pepperoni and Lebanon bologna), pods of broad beans (Fava beans) and yoghurt. Excessive amounts of caffeine and chocolate may also cause hypertensive reactions.
Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics (including pethidine and propoxyphene). Excitation seizures, delirium, hyperpyrexia, circulatory collapse, coma and death have been reported in patients receiving MAO inhibitor therapy who have been given a single dose of pethidine. Phenelzine sulfate should not be administered together with or in rapid succession to other MAO inhibitors, or dibenzazepine derivative drugs, because hypertensive crises and convulsive seizures, fever, marked sweating, excitation, delirium, tremor, coma and circulatory collapse may occur. Dibenzazepine derivative drugs include nortriptyline hydrochloride, amitriptyline hydrochloride, perphenazine, clomipramine hydrochloride, desipramine hydrochloride, imipramine hydrochloride, doxepin hydrochloride, carbamazepine, cyclobenzaprine hydrochloride, amoxapine hydrochloride, maprotiline hydrochloride, trimipramine maleate, protriptyline hydrochloride.
At least 10 days should elapse between the discontinuation of another MAO inhibitor and the institution of phenelzine sulfate.
MAO inhibitors, including phenelzine sulfate, potentiate hexobarbital hypnosis in animals. Therefore, barbiturates should be given at a reduced dose with phenelzine sulfate.
MAO inhibitors inhibit the destruction of serotonin and noradrenaline, which are believed to be released from tissue stores by rauwolfia alkaloids. Accordingly, caution should be exercised when rauwolfia is used concomitantly with an MAO inhibitor, including phenelzine sulfate. Phenelzine sulfate should not be used in combination with buspirone hydrochloride, since several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone hydrochloride.
At least 10 days should elapse between the discontinuation of phenelzine sulfate and the institution of another antidepressant or buspirone hydrochloride.
There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotonin reuptake inhibitors or venlafaxine hydrochloride has been combined with an MAO inhibitor. Therefore, phenelzine sulfate should not be used in combination with venlafaxine hydrochloride or serotonin reuptake inhibitors.
Before initiating phenelzine sulfate after using other serotonin reuptake inhibitors, a sufficient amount of time must be allowed for clearance of the serotonin reuptake inhibitor and its active metabolites. Allow at least five weeks between discontinuation of fluoxetine and initiation of phenelzine sulfate and at least 10 days between discontinuation of phenelzine sulfate and initiation of fluoxetine, or other serotonin reuptake inhibitors.
The combination of MAO inhibitors and tryptophan has been reported to cause behavioural and neurological symptoms including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperflexia, shivering, ocular oscillations and Babinski signs.

Adverse Effects

Phenelzine sulfate is a potent inhibitor of monoamine oxidase. Because this enzyme is widely distributed throughout the body, diverse pharmacological effects can be expected to occur. When they occur, such adverse effects can be mild, moderate or severe (see below), and can be minimised by adjusting dosage.
Common side effects include:

Nervous system.

Dizziness, headache, drowsiness, sleep disturbances (including insomnia and hypersomnia), fatigue, weakness, tremors, twitching, myoclonic movements, hyper-reflexia.

Gastrointestinal.

Constipation, dry mouth, gastrointestinal disturbances, elevated serum transaminases (without accompanying signs and symptoms).

Metabolic.

Weight gain.

Cardiovascular.

Postural hypotension, oedema.

Genitourinary.

Sexual disturbances, i.e. anorgasmia and ejaculatory disturbances.

Special senses.

Blurred vision.
Less common mild to moderate side effects (some of which have been reported in a single patient or by a single physician) include:

Nervous system.

Jitteriness, nervousness, palilalia, euphoria, nystagmus, paraesthesias, confusion, hallucinations, behavioural changes.

Genitourinary.

Urinary retention.

Metabolic.

Hypernatraemia.

Haematological.

Blood dyscrasias.

Cardiovascular.

Arrhythmias.

Dermatological.

Pruritus, skin rash, sweating.

Special senses.

Glaucoma.
Of the more severe side effects that have been reported with any consistency, hypomania has been the most common. This reaction has been largely limited to patients in whom disorders characterised by hyperkinetic symptoms coexist with, but are obscured by, depressive affect; hypomania usually appeared as depression improved. If agitation is present, it may be increased with phenelzine sulfate. Hypomania and agitation also have been reported at higher than recommended doses, or following long-term therapy.
Although reported less frequently, and sometimes only once, additional severe side effects include:

Nervous system.

Ataxia, shock-like coma, toxic delirium, manic reaction, delusional parasitosis, convulsions, acute anxiety reaction, precipitation of schizophrenia, acute dystonic reaction, sensorimotor peripheral neuropathy, speech blockade, transient respiratory and cardiovascular depression following ECT, neuroleptic malignant syndrome (occasionally fatal).

Gastrointestinal.

To date, fatal progressive necrotising hepatocellular damage has been reported infrequently; reversible jaundice.

Haematological.

Leucopenia.

Immunological.

Lupus-like illness.

Metabolic.

Inappropriate ADH secretion; hypermetabolic syndrome (which may include, but is not limited to, hyperpyrexia, tachycardia, tachypnoea, muscular rigidity, elevated CK levels, metabolic acidosis, hypoxia and coma and may resemble an overdose).

Respiratory.

Oedema of the glottis.

General.

Fever associated with increased muscle tone.
The most serious reactions to phenelzine sulfate involve changes in blood pressure.

Hypertensive crises.

The most important reaction associated with phenelzine sulfate administration is the occurrence of hypertensive crises, which have sometimes been fatal.
These crises are characterised by some or all of the following symptoms: occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea, vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), dilated pupils and photophobia. Either tachycardia or bradycardia may be present and can be associated with constricting chest pain.

Note.

Intracranial bleeding has been reported in association with the increase in blood pressure.
Blood pressure should be observed frequently to detect evidence of any pressor response in all patients receiving phenelzine sulfate. Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headaches during therapy.

Recommended treatment in hypertensive crisis.

If a hypertensive crisis occurs, phenelzine sulfate should be discontinued immediately and therapy to lower blood pressure should be instituted immediately. On the basis of present evidence, phentolamine is recommended. (The dosage reported for phentolamine is 5 mg intravenously). Care should be taken to administer this drug slowly in order to avoid producing an excessive hypotensive effect. Fever should be managed by means of external cooling.
Withdrawal may be associated with nausea, vomiting and malaise.
An uncommon withdrawal syndrome following abrupt withdrawal of phenelzine sulfate has been infrequently reported. Signs and symptoms of this syndrome generally commence 24 to 72 hours after drug discontinuation and may range from vivid nightmares with agitation to frank psychosis and convulsions. This syndrome generally responds to reinstitution of low dose phenelzine sulfate therapy followed by cautious downward titration and discontinuation.

Dosage and Administration

Use in children and adolescents (< 18 years).

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

Initial dose.

The usual starting dose of phenelzine sulfate is one tablet (15 mg) three times a day.

Early phase treatment.

Dosage should be increased to at least 60 mg per day at a fairly rapid pace consistent with patient tolerance. It may be necessary to increase dosage up to 90 mg per day to obtain sufficient MAO inhibition. Many patients do not show a clinical response until treatment at 60 mg has been continued for at least 4 weeks.

Maintenance dose.

After maximum benefit from phenelzine sulfate is achieved, dosage should be reduced slowly over several weeks. Maintenance dose may be as low as one (1) tablet, 15 mg, a day or every other day, and should be continued for as long as required.

Overdosage

Note.

For management of hypertensive crisis see Adverse Effects. Accidental or intentional overdosage may be more common in patients who are depressed. It should be remembered that multiple drugs and/or alcohol may have been ingested.
Depending on the amount of overdosage with phenelzine sulfate, a varying and mixed clinical picture may develop, including signs and symptoms of central nervous system and cardiovascular stimulation and/or depression. Signs and symptoms may be absent or minimal during the initial 12 hour period following ingestion and may develop slowly thereafter, reaching a maximum in 24-48 hours. Death has been reported following overdosage. Therefore, immediate hospitalisation with continuous patient observation and monitoring throughout this period is essential.
Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonus, rigidity, convulsions and coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis and cool, clammy skin.

Treatment.

Intensive symptomatic and supportive treatment may be required. Induction of emesis or gastric lavage with instillation of charcoal slurry may be helpful in early poisoning, provided the airway has been protected against aspiration. Signs and symptoms of central nervous system stimulation, including convulsions, should be treated with diazepam, given slowly intravenously. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids. Vasopressors are best avoided. It should be noted that adrenergic agents may produce a markedly increased pressor response.
Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential.
There are no data on the lethal dose in man. The pathophysiological effects of massive overdosage may persist for several days, since the drug acts by inhibiting physiological enzyme systems. With symptomatic and supportive measures, recovery from mild overdosage may be expected within 3 to 4 days. Haemodialysis, peritoneal dialysis and charcoal haemoperfusion may be of value in massive overdosage, but sufficient data are not available to recommend their routine use in these cases.
Toxic blood levels of phenelzine have not been established, and assay methods are not practical for clinical or toxicological use.

Presentation

Tablets, 15 mg (orange), 100 tablets. Contained within a white, high density polyethylene (HDPE) bottle fitted with a white polypropylene (PP) child resistant cap with a tamper evident liner.

Storage

Store at 2°C to 8°C. (Refrigerate. Do not freeze.)

Poison Schedule

S4.