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

Logo ASPEN MIRTAZAPINE 15 mg (Film-coated tablet)
ASPEN MIRTAZAPINE 30 mg (Film-coated tablet)
ASPEN MIRTAZAPINE 45 mg (Film-coated tablet)

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

ASPEN MIRTAZAPINE 15 mg (Film-coated tablet)
ASPEN MIRTAZAPINE 30 mg (Film-coated tablet)
ASPEN MIRTAZAPINE 45 mg (Film-coated tablet)

COMPOSITION:
Each ASPEN MIRTAZAPINE 15 mg film-coated tablet contains 15 mg
Mirtazapine.
Each ASPEN MIRTAZAPINE 30 mg film-coated tablet contains 30 mg Mirtazapine.
Each ASPEN MIRTAZAPINE 45 mg film-coated tablet contains 45 mg Mirtazapine.

PHARMACOLOGICAL CLASSIFICATION:
A.1.2. Pyschoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION:
Mirtazapine is a tetracyclic antidepressant, belonging to the piperazino-azapine group of compounds.
Mirtazapine is centrally acting as a pre-synaptic alpha
2-antagonist, which increases the central noradrenergic and serotonergic neurotransmission. It limits the effectiveness of inhibitory alpha2-adrenergic heteroreceptors on serotonergic neurons as well as inhibitory alpha2-autoreceptors and 5-HT2A heteroreceptors on noradrenergic neurons, which enhances the release of both amines.
It has antagonistic effects at several post synaptic serotonin receptor types (including 5-HT
2A, 5-HT2C, and 5-HT3 receptors) and can produce gradual down regulation of 5-HT2A receptors. These several actions probably contribute to the antidepressant effect. Mirtazapine is also a histamine Hl-receptor antagonist, and correspondingly, relatively sedating.
Pharmacokinetics
Mirtazapine is well absorbed (bioavailability = 50%) from the gastrointestinal tract with peak plasma levels occurring after about two hours. Plasma protein binding is about 85%. Mirtazapine is extensively metabolised in the liver and the major bio-transformation pathways are demethylation and oxidation followed by glucuronide conjugation; cytochrome P450 isoenzymes involved are CYP2D6, CYP1A2 and CYP3A4. The N-desmethyl metabolite is pharmacologically active. The mean plasma elimination half-life is 20-40 hours. Elimination is via urine (75%) and faeces (15%). Mirtazapine displays linear pharmacokinetics within the recommended dose range.

INDICATIONS:
Treatment of major depressive illness.

CONTRA-INDICATIONS:
Hypersensitivity to ASPEN MIRTAZAPINE. Pregnancy and lactation, as there is insufficient clinical data available. Children, as insufficient clinical data are available.

WARNINGS:
ASPEN MIRTAZAPINE should be used with caution in patients with epilepsy, hepatic or renal insufficiency, and cardiac disorders such as conduction disturbances, angina pectoris, and recent myocardial infarction, as well as in patients with hypotension. Careful dosage as well as regular and careful monitoring is necessary in these patients.
Caution should also be exercised in patients with diabetes mellitus, psychoses and those with a history of bipolar disorder. Treatment should be stopped if jaundice develops.
Patients should be advised to report any of the following symptoms during treatment: fever, sore throat, stomatitis or other signs of infection. These may be signs of bone marrow depression (neutropenia, agranulocytosis). Treatment should be stopped and a blood count performed.
Patients with major depressive disorder, both adults and children, may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. A causal role, however, for antidepressant medicine in inducing such behaviour has not been established. Patients being treated with ASPEN MIRTAZAPINE should, nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy or at any time of dose changes, either increases or decreases.
Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorders should be observed when treating patients with other psychiatric and non-psychiatric disorders.
The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania and mania. Although a causal link between the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing ASPEN MIRTAZAPINE, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patients presenting symptoms.
If the decision is made to discontinue treatment, ASPEN MIRTAZAPINE should be tapered (see SPECIAL PRECAUTIONS and DOSAGE AND DIRECTIONS FOR USE).

INTERACTIONS:
MAOI
: ASPEN MIRTAZAPINE should not be used concomitantly or within two weeks of discontinuing a MAOI.
Alcohol: ASPEN MIRTAZAPINE may potentiate the central nervous depressant action of alcohol and patients should therefore be advised to avoid alcohol.
Anxiolytics or hypnotics: Use of ASPEN MIRTAZAPINE may potentiate the sedative effects of anxiolytics and hypnotics. Caution should be taken when these drugs are prescribed together with ASPEN MIRTAZAPINE.

PREGNANCY AND LACTATION:
ASPEN MIRTAZAPINE is contra-indicated in pregnancy and lactation.

DOSAGE AND DIRECTIONS FOR USE:
Tablets should be taken orally.
ASPEN MIRTAZAPINE should be given in initial dose of 15 mg, which may be increased gradually according to clinical response. The usual effective dose lies within the range of 15 to 45 mg. Daily doses may be given as a single dose, preferably at bedtime, or in 2 equally divided doses.
Changes in dose should be made at intervals of at least 1 to 2 weeks because of the long half-life. For treatment of acute depressive episodes, treatment should be continued for at least 6 months.
ASPEN MIRTAZAPINE should be withdrawn gradually to reduce the risk of withdrawal symptoms.
The clearance of mirtazapine may be decreased in elderly patients and in patients with renal or hepatic impairment. This should be taken into account when prescribing ASPEN MIRTAZAPINE to this category of patients.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Body as a whole:
Asthenia, flu like syndrome, increased sweating.
Nervous system disorders:
Drowsiness or sedation, paraesthesia, tremor, vertigo, epileptic seizures, dizziness, headache, nightmares, agitation, mania, hallucinations, convulsions, tremor, myoclonus and restless legs syndrome.
Metabolism and nutritional disorders:
An increase in appetite and weight gain, dry mouth, constipation, nausea, vomiting, thirst, bitter taste (in the mouth)
Vascular disorders:
Oedema, peripheral oedema and postural hypotension.
Skin and subcutaneous disorders:
Exanthema, oedema.
Hepatobiliary disorders:
Increases in liver enzyme level have been reported. Jaundice may occur.
Blood and lymphatic system disorders:
Reversible agranulocytosis, leucopenia and granulocytopenia, orthostatic hypotension.
Musculoskeletal and connective tissue disorders:
Arthralgia and myalgia.

Special precautions:
Renal and urinary disorders: ASPEN MIRTAZAPINE has weak antimuscarinic activity, therefore caution should be exercised in patients with micturition disturbances and
Eye disorders: closed angle glaucoma, and raised intra-ocular pressure.
Psychiatric disorders: Patients should be closely monitored during early therapy until improvement in depression is observed because suicide is an inherent risk in depressed patients.
ASPEN MIRTAZAPINE may decrease alertness, judgement, thinking and concentration. Therefore operating machinery or driving a vehicle should be avoided during treatment.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
There is no specific antidote for ASPEN MIRTAZAPINE.
Treatment is symptomatic and supportive.

IDENTIFICATION:
ASPEN MIRTAZAPINE 15 mg film-coated tablets are 8 mm normal convex, yellow, film-coated tablets debossed "MR" score-line "15" on the one side and "G" on the other.
ASPEN MIRTAZAPINE 30 mg film-coated tablets are 9,5 mm normal convex, buff, film-coated tablets debossed "MR" score-line "30" on the one side and "G" on the other.
ASPEN MIRTAZAPINE 45 mg film-coated tablets are 11 mm normal convex, white, film-coated tablets with "MR and 45" (no score-line) on the one side and "G" on the other.

PRESENTATION:
Packs of 28's or 30's in plain, aluminium foil (silver with black print) and clear, colourless PVC/PVDC blister packs (3 x blister strips of 10 tablets or 2 x blister strips of 14 tablets) - the blister should be kept in the unit carton until required for use; or opaque, grey/white, polypropylene securitainers with grey/white LDPE, snap-on caps (tamper evident strips) plus white, polyethylene ullage filler (jayfilla).

STORAGE INSTRUCTIONS:
Store below 25°C, in well closed containers. Protect from light and moisture. KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
ASPEN MIRTAZAPINE 15 mg - 41/1.2/0142
ASPEN MIRTAZAPINE 30 mg - 41/1.2/0143
ASPEN MIRTAZAPINE 45 mg - 41/1.2/0144

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
19 January 2007

        LT1432AA

New addition to this site: February 2008
Source: Pharmaceutical Industry

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