MOCLOBEMIDE

Adults:

Initial usual dose 300 mg, administered in divided doses after meals. The tablets are for oral administration and should be taken with fluid. If necessary, the daily dose can be increased to 600 mg per day. However, the dose should not be increased during the 1st week of treatment, because the bioavailability increases during this time and a clinical effect may not be seen for 1-3 weeks.

In individual cases, the therapeutic dose can be gradually reduced to 150 mg per day, depending on effect.

Duration of treatment:

Treatment with moclobemide should be continued for at least 4-6 weeks to be able to judge the efficacy of moclobemide. Treatment with moclobemide should preferably be continued for a symptom free period of 4-6 months. Then treatment can be gradually tapered off.

Antidepressants, particularly MAOIs, should be withdrawn gradually to reduce the risk of withdrawal symptoms.

Elderly:

No special dose adjustment is required Paediatric population: In view of the lack of clinical data available, moclobemide is not recommended for use in children and adolescents under the age of 18.

Renal/hepatic impairment:

Patients with reduced renal function do not require a special dose adjustment. In patients with impaired hepatic function, the daily dose of moclobemide should be reduced to a half or one third.

The undesirable effects observed during treatment with moclobemide are observed mainly during the first few weeks of treatment and regress subsequently, concomitantly with improvement of the depressive episode. This is particularly so for some of the undesirable effects that are related to the very nature of the depressive illness such as feelings of anxiety, agitation or irritability, mood switch with mania or delirium.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000), not known (cannot be estimated from the available data).

Metabolism and nutrition disorders Rare: decreased appetite*, hyponatraemia* Psychiatric disorders Very common: sleep disorders Common: agitation, anxiety, restlessness Uncommon: suicidal ideation, confusional state (these have resolved quickly on discontinuation of therapy) Rare: suicidal behaviors, delusion* Nervous system disorders Very common: dizziness, headache Common: paraesthesia Uncommon: dysgeusia Eye disorders Uncommon: visual impairment Cardiac disorders Moclobemide can cause QT interval prolongation.

QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia.

Vascular disorders:

Common: hypotension Uncommon: flushing Gastrointestinal disorders Very common: nausea, dry mouth Common: diarrhoea, constipation, vomiting Skin and subcutaneous tissue disorders Common: Rash Uncommon: oedema, pruritus, urticaria Reproductive system and breast disorders Very rare: galactorrhea General disorders and administration site conditions: Common: irritability Uncommon: asthenia Investigations: Rare: Serotonin syndrome* (co-administered with drugs that enhance serotonin, such as serotonin re-uptake inhibitors and many other antidepressants), Increased hepatic enzymes (without associated clinical sequelae).

*: Adverse reactions that were not reported in clinical studies but were only reported post-marketing are indicated by an asterix (*) 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. uk/yellowcard).

Warnings As with other antidepressants, treatment may exacerbate the schizophrenic symptoms of depressive patients with schizophrenic or schizoaffective psychoses. If possible, therapy with long-acting neuroleptics should be continued in such patients.

Generally during therapy with moclobemide, special dietary restrictions are not necessary. Since hypersensitivity to tyramine may exist in some patients, all patients should be advised to avoid the consumption of large amounts of tyramine-rich food.

Hypersensitivity may occur in susceptible individuals. Symptoms may include rash and edema. Theoretical pharmacological considerations indicate that MAO inhibitors may precipitate a hypertensive reaction in patients with thyrotoxicosis or pheochromocytoma.

As experience with moclobemide in this population group is lacking, caution should be exercised with regard to prescribing moclobemide. In patients receiving moclobemide, additional drugs that enhance serotonin such as many other antidepressants, particularly in multiple-drug combinations, should be given with caution.

g. 5). 5). 5). St. John’s wort (Hypericum)-containing phytotherapeutic products should be used with care in combination with moclobemide as this may increase the serotonin concentration. Moclobemide contains lactose and sodium Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

This medicinal product contains less than 1 mmol (23 mg) sodium per film- coated tablet, that is to say essentially ‘sodium-free’. Precautions 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.

Other psychiatric conditions for which Moclobemide is prescribed can also be associated with an increased risk of suicide – related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

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.

Insomnia or nervousness or jitteriness at the beginning of treatment with moclobemide can justify a dose reduction or temporary symptomatic treatment. In case of occurrence of mania or hypomania, or the onset of early symptoms of those reactions (grandiosity, hyperactivity (including increased speech), reckless impulsivity), treatment with moclobemide will be interrupted and alternative treatment will be initiated.

Depressive patients with excitation or agitation as the predominant clinical symptoms should either not be treated with moclobemide or only in combination with a sedative for not more than 2-3 weeks. If a depressive episode is treated in bipolar disorders, manic episodes may be provoked, in such cases treatment with moclobemide should be stopped.

Patients with hypertension should be closely monitored when being treated with moclobemide. Patients should be advised to avoid sympathomimetic agents, such as ephedrine, pseudoephedrine and phenylpropanolamine (contained in many proprietary cough medicinal products).

Patients should also be advised that if they require surgery they should inform the anaesthesiologist that they take moclobemide. Caution should be exercised in patients with congenital long QT syndrome or with a history of cardiac disorders (including disturbances of conduction, arrhythmia).

Concomitant administration of QT prolonging medicinal products should be avoided. 5). If concomitant treatment with buprenorphine or buprenorphine/naloxone is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.

1. - Acute confusional states. - Patients with phaeochromocytoma. - Moclobemide should not be used in pediatrics at present, as clinical experience of the drug's action in children is lacking. 5): • Selegiline • Linezolid • Triptans • Pethidine • Tramadol • Bupropion • Dextromethorphan • 5-HT re-uptake inhibitors or other antidepressants (including tricyclic antidepressants)