AURORIX®
Moclobemide 150mg and 300mg tablets
Antidepressant
Composition
Active ingredient
moclobemide.
Tablets 150 mg and 300 mg.
Excipients
Kernel
Lactose, maize starch, polyvidone, sodium starch glycollate, magnesium stearate.
Film coating
Methylhydroxypropylcellulose, ethylcellulose, polyethylene glycol, talc.
The Aurorix 150mg tablets also contain the colourants titanium dioxide (E171) and yellow iron oxide (E172) in the film coat.
The Aurorix 300mg tablets contain the colourant titanium oxide (E171) in the film coat.
Appearance
Tablets containing 150mg moclobemide are pale yellow and have "ROCHE 150" on one side. Tablets are oval shaped, about 15mm by 8mm, with a break bar on the other side.
Tablets containing 300mg moclobemide are white to off-white and have "ROCHE 300" on one side. Tablets are oval shaped, about 15mm by 8mm, with a break bar on the other side.
Properties and effects
Aurorix is an antidepressant which affects the brain monoaminergic neurotransmitter system through reversible inhibition of monoamine oxidase, preferentially of type A. The metabolism of norepinephrine, dopamine and serotonin is thus decreased, and this leads to increased extracellular concentrations of these neuronal transmitters. As a result of its elevating effect on mood and psychomotor activity, Aurorix relieves symptoms such as dysphoria, exhaustion, lack of drive and inability to concentrate. These effects most often appear within the first week of therapy. Aurorix also relieves symptoms related to social phobia.
Though Aurorix has no sedative properties, it improves the quality of sleep in most depressive patients within days. Aurorix does not impair alertness.
Short-term and long-term animal studies indicate low toxicity. No cardiac toxicity has been observed.
Pharmacokinetics
Absorption
After oral administration, moclobemide is completely absorbed from the gastrointestinal tract into the portal circulation. Peak plasma concentrations of moclobemide are reached within 1 hour of administration. Hepatic first-pass metabolism reduces the systemically available dose fraction (bioavailability) in a dose-dependent manner. However, saturation of these metabolic pathways during the first week of dosing (300-600 mg/day) results in essentially complete oral bioavailability thereafter. Plasma concentrations following multiple doses of moclobemide increase over the first week of therapy and then stabilize. When the daily dose is increased, there is a greater-than-proportional increase in steady-state concentrations.
Distribution
Moclobemide is lipophilic. The apparent volume of distribution (Vss) is about 1.0 l/kg. Binding of the medicine to plasma proteins, mainly albumin, is relatively low (50%). Insignificant amounts are secreted in human breast milk.
Metabolism
Moclobemide is almost entirely metabolized before being eliminated. Metabolism occurs largely via oxidative reactions on the morpholine moiety of the molecule. Active metabolites are present only at very low concentrations in the systemic circulation in man. The major metabolites present in plasma are a lactam derivative and an N-oxide derivative. Moclobemide has been shown to be metabolized in part by the polymorphic isoenzymes CYP2C19 and CYP2D6. Thus, in genetically or drug-induced (via metabolic inhibitors) poor metabolizers, metabolism of moclobemide may be affected. Two studies conducted to investigate the magnitude of these effects suggested that, due to the presence of multiple alternative metabolic pathways, they are of no clinical significance and should not necessitate dosage modification.
Elimination
Moclobemide is rapidly eliminated by metabolic processes. Total clearance is approximately 20-50 l/hour. The mean elimination half-life during multiple dosing (300 mg twice a day.) is approximately 3 hours and generally ranges from 2-4 hours in most patients. Less than 1% of a dose is excreted renally in unchanged form. Metabolites are likewise eliminated renally.
Pharmacokinetics in special populations
Elderly
Absorption and disposition parameters are unchanged in the elderly.
Patients with renal impairment
Renal disease does not alter the elimination characteristics of moclobemide.
Patients with hepatic impairment
In advanced liver insufficiency, the metabolism of moclobemide is reduced (see Special dosage instructions).
Indications and usage
Aurorix is indicated for the treatment of depressive syndromes and social phobia.
Dosage and administration
Depressive syndromes
The recommended dose range of Aurorix is 300-600 mg. Treatment with moclobemide can begin with the full therapeutic dose of 300-450 mg in 2 or 3 oral divided doses after meals. The dose may be increased to 600 mg/day for severe depression.
The dose should not be raised until after the first week, as bioavailability increases during this period (see Pharmacokinetics). The individual response may allow a reduction of the daily dose.
Treatment should continue for at least 4-6 weeks in order to assess efficacy.
Social phobia
The recommended dose of Aurorix is 600 mg/day, given in 2 divided doses. Treatment with 600 mg/day should continue for 8-12 weeks in order to assess the efficacy of the medicine. Social phobia may be a chronic condition and it is reasonable to consider continuation of treatment for a responding patient. Results of long-term studies indicate that the efficacy of treatment with Aurorix is maintained with continued use. Patients should be re-evaluated periodically to determine need for further treatment.
Patients can be switched to moclobemide from other antidepressants and vice versa without a washout period. When switching to Aurorix, the dose should not exceed 300 mg/day during the first week. See Interactions.
Special dosage instructions
The dose should be taken after a meal. The dose of Aurorix does not need to be specially adjusted in elderly patients or patients with reduced renal function. When hepatic metabolism is severely impaired by hepatic disease or inhibited by a medicine that inhibits microsomal mixed function oxidase activity (e.g. cimetidine), the daily dose of Aurorix should be reduced to half or one third (see Pharmacokinetics in special populations).
Children
There are not yet sufficient data to be able to recommend the use of moclobemide in children.
Contraindications
Use in patients with known hypersensitivity to moclobemide or to any component of the product.
Acute confusional states
Aurorix should not be used in pediatrics at present, as clinical experience of the medicine's action in children is lacking.
Co-administration of Aurorix with selegiline is contraindicated. (See also Interactions.)
Precautions
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.
As is usual in antidepressant therapy, patients with suicidal tendencies should be closely monitored.
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 Aurorix, additional medicines that enhance serotonin, such as many other antidepressants, particularly in multiple combinations, should be given with caution. This is particularly true for clomipramine (see Interactions).
Impairment of performance in activities requiring complete mental alertness (e.g. driving a motor vehicle) is generally not to be expected with Aurorix. However, as is true when starting any new medication, care should be taken with regard to such activities during early treatment.
Pregnancy, nursing mothers
Reproduction studies in animals have not revealed any risk to the foetus but the safety of Aurorix in human pregnancy has not been established. Therefore, the benefits of therapy during pregnancy should be weighed against possible risks to the foetus.
Although only a small amount of moclobemide passes into breast milk (approx. 1/30 of the maternal dose when correcting for bodyweight differences), the benefits of continuing therapy for a nursing mother should be weighed against possible risks to the child.
Undesirable effects
The following undesirable effects have been observed: sleep disturbances, agitation, feelings of anxiety, irritability, dizziness, headache, paresthesia, dry mouth, visual disturbances, gastrointestinal complaints and skin reactions (such as rash, pruritus, urticaria and flushing). Some undesirable effects can be due to underlying symptoms of the illness and disappear in most cases with continuation of the therapy. Isolated cases of confusion have been seen; these have resolved quickly on discontinuation of therapy.
There appears to be a low incidence of raised liver enzymes without associated clinical sequelae.
Interactions
Co-administration of Aurorix with selegiline is contraindicated.
In animals, moclobemide potentiates the effects of opiates. A dosage adjustment may therefore be necessary for these medicines. The combination with pethidine is not recommended.
Since the action of Aurorix is selective and reversible, its propensity to interact with tyramine is slight and short-lasting, as pharmacological studies in animals and man have shown (see Precautions). The potentiation of the pressor effect was even lower or did not occur when moclobemide was administered after a meal.
Cimetidine prolongs the metabolism of moclobemide (see Dosage and Administration).
The pharmacologic action of systemic regimens of sympathomimetic agents may possibly be intensified and prolonged by concurrent treatment with moclobemide.
In patients receiving Aurorix, additional medicines that enhance serotonin, such as many other antidepressants, particularly in multiple combinations, should be given with caution. This is particularly true for clomipramine. This is because in isolated cases there has been a combination of serious symptoms and signs, including hyperthermia, confusion, hyperreflexia and myoclonus, which are indicative of serotonergic overactivity (serotonergic syndrome). Should such combined symptoms occur, the patient should be closely observed by a physician (and if necessary hospitalized) and appropriate treatment given. Treatment with a tricyclic or other antidepressant could be initiated immediately after withdrawal of Aurorix (i.e. without a wash-out period) and vice versa, provided similar caution is observed. When switching to Aurorix, the dose should not exceed 300 mg/day during the first week (see Dosage and Administration).
Isolated cases of severe central nervous system adverse reactions have been reported after co-administration of Aurorix and dextromethorphan. Since cough and cold medicines may contain dextromethorphan, they should not be taken without prior consultation with the physician, and if possible, alternatives not containing dextromethorphan should be given.
Overdosage
Overdoses of moclobemide alone induce generally mild and reversible signs of CNS and gastrointestinal irritation, which do not need particular intervention. Treatment should be aimed at support of vital functions.
As with other antidepressants, mixed overdoses of moclobemide with other drugs (e.g. with other CNS-acting medicines) could be life-threatening. Therefore, patients should be hospitalized and closely monitored so that appropriate treatment may be given.
Special Remarks
Stability
Store below 30°C.
This medicine should not be used after the expiry date shown on the pack.
Packs
Tablets 150mg in packs of 100's
Tablets 300mg in packs of 60's
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