INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ADCO-MOCLOBEMIDE 150 mg TABLETS
ADCO-MOCLOBEMIDE 300 mg TABLETS

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

ADCO-MOCLOBEMIDE 150 mg TABLETS
ADCO-MOCLOBEMIDE 300 mg TABLETS

COMPOSITION:
Each Adco-Moclobemide 150 mg tablet contains: 150 mg moclobemide
Each Adco-Moclobemide 300 mg tablet contains: 300 mg moclobemide

PHARMACOLOGICAL CLASSIFICATION:
A 1.2 Psychoanaleptics (antidepressants).

PHARMACOLOGICAL ACTION:
Moclobemide is an antidepressant that affects the monoaminergic cerebral neurotransmitter system by means of a selective reversible inhibition of monoamine oxidase preferentially of type A.
The metabolism of noradrenaline, dopamine and serotonin is decreased by this effect and this leads to increased extracellular concentrations of these neuronal transmitters.
After oral administration, moclobemide is absorbed from the gastro-intestinal tract into the portal blood. A hepatic first-pass effect reduces the systemically available dose fraction [bioavailability (F)] in a dose-dependent manner (40 - 80%). This reduction is more pronounced after single (F: 60%) than after multiple (F: >80%) doses. Due to its lipophilic nature, moclobemide is extensively distributed in the body with a volume of distribution (Vss) of about 1,2 litre/kg. Binding of moclobemide to plasma proteins, mainly albumin, is relatively low (approximately 50%).
Peak plasma concentrations of moclobemide are reached within 0,5 to 2 hours of dosage. After multiple dosing, plasma concentrations of moclobemide increase in the first week of therapy and remain stable thereafter. When the daily dose is increased, there is a more than proportional increase in steady-state concentrations.
Moclobemide is almost entirely metabolised in the liver, mainly by oxidative reactions on the morpholine fragment of the molecule, and less than 1% of a dose is excreted renally unchanged. Degradation products with pharmacological activity, observed in in-vitro oranimal experiments, are present in the systemic circulation in man at very low concentrations only. Moclobemide is rapidly eliminated from the body. Blood clearance is approximately 20-50 litres/hour. The elimination half-life of moclobemide is two to four hours with a slight increase at increased doses.

INDICATIONS:
Major depression.
Social phobia in patients that are disabled by this condition.

CONTRA-INDICATIONS:
Known hypersensitivity to moclobemide.
In patients with acute confusional states and those with phaeochromocytoma.
The safety in children has not been established.
Co-administration of moclobemide with selegiline.
Co-administration with other medicines that increase serotonin. These agents should not be administered in close temporal association to each other.
Pregnancy: Safety in pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE:
The recommended dose range of moclobemide is 300 - 600 mg daily, usually administered in two to three divided doses. The tablets should be taken immediately after a meal. The initial dose is 300 mg daily. The initial dose of 300 mg daily should not be exceeded during the first week of treatment as bioavailability increases during this period (see pharmacological action).
The individual response may allow a reduction of the daily dose to 150 mg.
Adco-Moclobemide dosage does not need to be specially adjusted in elderly patients or patients with reduced renal function.
Social phobia:
The recommended dose of moclobemide is 600 mg daily given in two divided doses. The moclobemide dose should be started at 300 mg daily and should be increased to 600 mg/day on day 4. Continuing the 300 mg daily dose for longer than 3 days is not recommended, as the efficacious dose is 600 mg daily. Treatment with 600 mg daily should continue for 6 - 8 weeks in order to assess the efficacy of the product. Moclobemide treatment should be withdrawn in patients not responding to 600 mg daily after 8 weeks of treatment. Social phobia may be a chronic condition and it is reasonable to consider the continuation of treatment for a responding patient. Results of long-term studies indicate that the efficacy of treatment with moclobemide is maintained with continued use. Patients should be periodically re-evaluated to determine need for further treatment.
When hepatic metabolism is severely impaired by hepatic disease or a medication that inhibits microsomal mono-oxygenase activity (e.g. cimetidine), normal plasma levels are achieved by reducing the daily dose of Adco-Moclobemide to one quarter to one third of the normal dose.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Sleep disturbances (including insomnia, difficulty in falling asleep and early waking), dizziness, agitation, irritability, restlessness and headache may occur. Gastro-intestinal disturbances include dry mouth, nausea, vomiting, constipation, diarrhoea and loss of appetite. Paraesthesia, visual disturbances and oedema have also been reported, and skin reactions include rash, pruritus, urticaria and flushing. Raised liver enzymes have been reported.
Patients with suicidal tendencies should be closely monitored at the commencement of treatment.
Care is also required in patients with thyrotoxicosis as moclobemide may theoretically precipitate a hypertensive reaction.
Performance in activities requiring complete mental alertness (e.g. driving a motor vehicle) may be slowed in certain patients. The individual reaction should, however, be monitored during early treatment.
Due to lack of clinical data, patients with schizophrenic or schizoaffective organic disorders should not be treated with moclobemide.
Hypertensive patients are advised to avoid large amounts of food and beverages with high tyramine content.
In patients receiving moclobemide, the additional use of other drugs that enhance serotonin, such as other antidepressants, particularly in multiple drug combinations, should be done with caution. This is particularly true for clomipramine, fluoxetine, paroxetine, etc. Hyperthermia, confusion, hyperreflexia and myoclonus, which are indicative of serotonergic overactivity, may occur with this combination. Should such combined symptoms occur, the patient should be closely observed by a physician (if necessary hospitalised) and appropriate treatment given.
Moclobemide should not be co-administered with serotonin (5-HT) re-uptake inhibitors (including tricyclic antidepressants, e.g. clomipramine). After stopping treatment with 5-HT re-uptake inhibitors, a time period equal to 4 - 5 half-life of the agent or active metabolite should elapse between stopping therapy and starting therapy with moclobemide.
Cases of severe central nervous system adverse reactions have been reported after co-administration of moclobemide and dextromethorphan. Since cough and cold medicines may contain dextromethorphan, they should not be taken without prior consultation with the doctor, such that non-dextromethorphan-containing alternatives may be given.
If a depressive episode is treated in bipolar disorders, manic episodes can be provoked.

INTERACTIONS:
In pharmacological studies (normal volunteers) moclobemide shows, due to its reversible inhibition of monoamine oxidase preferentially of type A, less interaction with tyramine than irreversible MAO inhibitors.
In animals, moclobemide potentiates the effects of opiates. A dosage adjustment may therefore be necessary for these drugs. The combination with pethidine is not recommended. Concomitant administration of ibuprofen and moclobemide to healthy volunteers did not result in a statistically significant interaction.
Cimetidine prolongs the metabolism of moclobemide. The normal dose of moclobemide should therefore be reduced to one quarter to one third the dose in patients taking cimetidine.
Treatment with a tricyclic or other antidepressants (except serotonergic re-uptake inhibitors including clomipramine) can be initiated without a washout period. When switching to moclobemide, the dose should not exceed 300 mg/day in the first week.
There is limited clinical experience on the concomitant use of Adco-Moclobemide with centrally acting anti-hypertensive agents and ganglion-blocking agents e.g. clonidine, methyldopa, guanethidine, and rauwolfia derivatives. The possibility exists that the pharmacological effect of sympathomimetic agents systemically administered may be potentiated and prolonged during concomitant treatment with moclobemide.
There is, to date, no experience with co-administration of moclobemide and buspirone in humans. In patients receiving moclobemide, additional medicines that enhance serotonin, such as many other antidepressants, particularly in multi-drug combinations, should not be given. This is particularly true for clomipramine. Cases of severe central nervous system adverse reactions have been reported after co-administration of moclobemide and dextromethorphan.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms of overdosage of moclobemide if taken alone includes: agitation, aggressiveness and behavioural changes. Treatment of this overdose should be aimed primarily at maintenance of the vital functions, and should include gastric lavage or emesis and fluid control.
Combination overdose (e.g. with medication which has an effect on the central nervous system) however, can lead to life-threatening situations. In these cases, the patient should be hospitalised and carefully monitored, so that adequate treatment can be applied.

IDENTIFICATION:
Adco-Moclobemide 150 mg Tablets:
White to off-white, round, odourless, film-coated tablets. The tablets are scored on both sides and embossed with “MCB 150”on one side.
Adco-Moclobemide 300 mg Tablets:
White to off-white, round, odourless, film-coated tablets. The tablets are scored on both sides and embossed with “MCB 300”on one side.

PRESENTATION:

Adco-Moclobemide 150 mg:	PVC/Aluminium blisters with 30, 60 or 100 tablets or HDPE tablet containers, containing 30, 50 or 100 tablets with child-resistant closures.
Adco-Moclobemide 300 mg:	PVC/Aluminium blisters with 30, 60 or 100 tablets or HDPE tablet containers, containing 30 or 60 tablets with child-resistant closures.

STORAGE INSTRUCTIONS:
Store below 25°C in a well-closed container, in a dry place, protected from light.
Do not remove the blister pack from the carton until required for use.
Keep out of reach of children.

REGISTRATION NUMBER:
Adco-Moclobemide 150 mg tablets: 35/1.2/0145
Adco-Moclobemide 300 mg tablets: 35/1.2/0146

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Adcock Ingram Limited
17 Harrison Avenue
Bryanston
2021

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
25.04.2003

New addition to this site: April 2004
Source: Pharmaceutical Industry
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