NARDIL Film coated tablet Ref.[8740] Active ingredients: Phenelzine

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Nardil should be withdrawn two weeks before elective surgery/dentistry.

Nardil should not be given with cocaine or local anaesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of Nardil and spinal anaesthesia should be kept in mind.

Nardil should be used only with great caution in agitated patients or those who have cardiovascular disease, epilepsy, blood dyscrasias, porphyria or diabetes; and in patients taking diuretics.

Blood pressure should be observed frequently to detect any pressor response and therapy discontinued if palpitations or frequent headaches occur.

Patients should also be closely followed for symptoms of postural hypotension. Hypotensive side effects have occurred in hypertensive as well as normotensive and hypotensive patients.

Due to the possibility of patients undergoing “Withdrawal Syndrome” (see section 4.8 Undesirable Effects) abrupt withdrawal of phenelzine should be avoided where possible.

Phenelzine may cause excessive stimulation in schizophrenic patients; in manic-depressive states it may result in a swing from a depressive to a manic phase.

Caution should be exercised if the patient undergoes concurrent electroconvulsive therapy (ECT).

Patients should be warned against self medication, particularly cold cures, cough cures, hay fever medications, anti-appetite medicines, weight-reducing preparations and “pep” pills and about potential food interactions.

Patients under treatment with Nardil should avoid high protein food that has undergone breakdown by ageing, fermentation, pickling, smoking or bacterial contamination. Patients should avoid cooked or plain cheese, Oxo, Bovril, Marmite, brewer’s yeast, etc. during treatment and up to 14 days after ceasing treatment. Flavoured textured vegetable protein, hung game, pickled herrings, dry sausage (salami, pepperoni etc.), liver, yoghurt, broad bean pods, fermented soya bean extract, and excessive amounts of chocolate may also present a hazard. Patients should not consume alcoholic drink or non-alcoholic beers, lagers and wines and excessive amounts of tea and coffee should be avoided.

Where a reaction between Nardil and certain foodstuffs occurs the intensity of the reaction is usually related to the tyramine content of the food. The reaction is now well recognised and serious hypertensive episodes are extremely rare. Should such a reaction occur, the hypertension should be controlled promptly by slow administration of phentolamine 5mg to 10mg IV repeated if necessary. Care should be taken to administer this drug slowly to avoid an excessive hypotensive effect.

Nardil may also potentiate the effects of alcohol.

Nardil may potentiate the action of pethidine, morphine, adrenaline, amphetamines and other sympathomimetic amines such as fenfluramine, ephedrine, phenylpropanolamine, dopamine and levodopa (see also Contraindications). Nardil may also potentiate the effects of antihypertensives, hypoglycaemic agents, sympathomimetics, anti-Parkinson drugs, antimuscarinics, local anaesthetics and CNS depressants, including barbiturates.

It is suggested that MAOIs are not administered at the same time as, or within 14 days of, treatment with amfebutamone (bupropion) or 5HT1 agonists.

It is suggested that MAOIs are not administered at the same time as anti-epileptics, altretamine, doxapram, tetrabenazine, oxypertine or clozapine.

The combination of MAOIs and tryptophan has been reported to cause behavioural and neurological symptoms.

Do not use during pregnancy, especially during the first and last trimesters, unless there are compelling reasons. There is no evidence as to drug safety in human pregnancy nor is there evidence from animal work that it is free from hazard.

It is not known if phenelzine is excreted in breast milk. Because of the potential for serious adverse effects to the infant, a decision should be made whether to discontinue the drug or not to breast-feed.

Produces adverse effects on driving ability.

Side-effects tend to be mild or moderate in severity, often subsiding as treatment continues, and can be minimised by adjusting dosage; rarely is it necessary to discontinue Nardil.

The most important reaction associated with Nardil is the occurrence of hypertensive crises, which have been associated with intracranial bleeding and have sometimes been fatal.

Cases of suicidal ideation and suicidal behaviours have been reported during Nardil therapy or early after treatment discontinuation (see Section 4.4).

Common side-effects include: dizziness, drowsiness, weakness and fatigue, oedema, gastro-intestinal disturbances (nausea, vomiting, dryness of the mouth, constipation), insomnia, blurred vision, adverse effects on driving ability, postural hypotension, twitching, myoclonic movements, hyperreflexia, elevated serum transaminases and anorgasmia.

Uncommon side-effects are headache, nervousness, euphoria, paraesthesia, sweating, increased appetite and weight, rash, pruritus, difficulty in micturition, muscle tremor, peripheral neuritis, behavioural changes, arrhythmias, convulsions, impotence and delayed ejaculation, purpura, blood dyscrasias, jitteriness, palilalia, nystagmus, hypernatraemia, glaucoma, lupus-like illness, confusion, hallucinations and elevated liver enzymes.

Other severe side-effects have been reported very rarely, including isolated reports in some cases. These include: ataxia, shock-like coma, toxic delirium, neuroleptic malignant syndrome (occasionally fatal), manic reaction, acute anxiety reaction, precipitation of schizophrenia, transient respiratory and cardiovascular depression following ECT, fatal progressive necrotising hepatocellular damage, reversible jaundice, hypermetabolic syndrome, oedema of the glottis and fever associated with increased muscle tone.

Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.

Withdrawal may be associated with nausea, vomiting and malaise. An uncommon withdrawal syndrome following abrupt withdrawal of Nardil has been infrequently reported. Signs and symptoms of this syndrome generally commence 24 to 72 hours after drug discontinuation and may vary from vivid nightmares and agitation to frank psychosis and convulsions. This syndrome generally responds to reinstitution of low-dose Nardil therapy followed by cautious downward titration and discontinuation.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

None known.