INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo CLORIX 150
CLORIX 300

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

CLORIX 150
CLORIX 300

COMPOSITION:
Each CLORIX 150 tablet contains 150 mg
moclobemide.
Each CLORIX 300 tablet contains 300 mg moclobemide.

PHARMACOLOGICAL CLASSIFICATION:
A: 1.2 Psychoanaleptics (antidepressants).

PHARMACOLOGICAL ACTION:       
Moclobemide is an antidepressant, which affects the monoaminergic cerebral neurotransmitter system by means of a reversible inhibition of monoamine oxidase preferentially of type A. The metabolism of dopamine, noradrenaline and serotonin is decreased by this effect, and this leads to increased extracellular concentrations of these neuronaltransmitters.
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 an apparent volume of distribution (V
ss) of about 1,2 litre/kg. Binding of the medicine to plasma proteins, mainly albumin, is relatively low (50%).
Peak plasma concentrations of the medicine are reached within 0,5 to 2 hours of dosage. After multiple dosing, plasma concentrations of moclobemide increase over 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.
The medicine is almost entirely metabolised before its elimination from the body: less than 1% of a dose is excreted renally in unchanged form. Metabolism occurs largely via oxidative reactions on the morpholine moiety of the molecule. The metabolites formed are eliminated renally.
Degradation products with pharmacological activity in vitro or animal 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 litre/hour, the elimination half-life 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. Acute confusional states. 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 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 therapy, as bioavailability increases during this period (see pharmacological action). The individual response may allow a reduction of the daily dose to 150 mg.
CLORIX 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/day, given in two divided doses. The moclobemide dose should be started at 300 mg/day and should be increased to 600 mg/day on day 4. Continuing the 300 mg/day dose for longer than 3 days is not recommended, as the efficacious dose is 600 mg/day. Treatment with 600 mg/day should continue for 6-8 weeks in order to assess the efficacy of the medicine. Moclobemide treatment should be withdrawn in patients not responding to 600 mg 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 impaired by hepatic disease or a drug (e.g. cimetidine) that inhibits microsomal mono-oxygenase activity, normal plasma levels are achieved by reducing the daily dose of CLORIX 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 may occur. Dizziness, headache, confusion, agitation, anxiety, irritability, restlessness, paraesthesiae, dry mouth, visual disturbances, gastro-intestinal complaints (such as nausea, vomiting, constipation, diarrhoea, loss of appetite), skin reactions (such as rash, pruritus, urticaria and flushing), and hypotension may also occur.
Raised liver enzymes have been reported.
Due to lack of clinical data, patients with schizophrenic or schizoaffective organic disorders should not be treated with moclobemide.
Patients with suicidal tendencies should be closely monitored at the commencement of treatment.
There appears to be a low incidence of raised liver enzymes without associated clinical sequelae.
Hypersensitivity may occur in susceptible individuals. Symptoms may include rash and oedema.
Hypertensive patients are advised to avoid large amounts of food and beverages with high tyramine content.
Theoretical pharmacological considerations indicate that MAO inhibitors may precipitate a hypertensive reaction in patients with thyrotoxicosis or pheaochromocytoma. As experience with moclobemide in this population group is lacking, caution should be exercised before prescribing moclobemide.
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.
In patients receiving moclobemide, the additional use of other drugs that enhance serotonin, such as many other antidepressants, particularly in multiple drug combinations, should be done with caution. This is particularly true for clomipramine, fluoxetine, paroxetine, etc. Hyperthermia, confusion, hyperflexia 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 those which are 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 physician, 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 of the dose in patients taking cimetidine. Treatment with a tricyclic or other antidepressant (except serotonergic re-uptake inhibitors including clomipramine) can be initiated without a wash out period. When switching to moclobemide, the dose should not exceed 300 mg/day during the first week.
There is limited clinical experience on the concomitant use of CLORIX 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.
In patients receiving moclobemide, additional medicines that enhance serotonin, such as many other antidepressants, particularly in multiple-drug combination, 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.
There is, to date, no experience with co-administration of moclobemide and buspirone in humans.
Lactation:A small amount of moclobemide passes into breast milk (approximately 1/30 of maternal dose when correcting for body weight differences), but safety has not been proven.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms of overdosage that have been observed are increasing agitation, aggressiveness and behavioural changes. Treatment of overdose should be aimed primarily at maintenance of the vital functions, and should include gastric lavage or emesis and fluid control.
Mixed overdoses with moclobemide (e.g. with other CNS-acting medicines) could be life-threatening. Therefore, patients should be hospitalised and closely monitored so that appropriate treatment may be given.

IDENTIFICATION:
CLORIX 150: A yellow, round, biconvex, film-coated tablet, scored on one side.
CLORIX 300: A white to yellowish white, oval, biconvex, film-coated tablet, scored on one side.

PRESENTATION:
CLORIX 150:         Blisters of 60 tablets.
CLORIX 300:         Blisters of 60 tablets.

STORAGE INSTRUCTIONS:
Store in a cool (below 25°C), dry place.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
CLORIX 150:         34/1.2/0169
CLORIX 300:         34/1.2/0170

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharma Dynamics (Pty) Ltd.
F02 Grapevine House
Steenberg Office Park
WESTLAKE
7945

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
21 November 2001

B072

New to this site: April 2003
Source: Pharmaceutical Industry
Current: November 2005
Source: Hospital Pharmacy

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