Consumer medicine information

Mirtanza ODT tablets

Mirtazapine

BRAND INFORMATION

Brand name

Mirtanza ODT

Active ingredient

Mirtazapine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mirtanza ODT tablets.

What is in this leaflet

This leaflet answers some common questions about Mirtanza ODT.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Mirtanza ODT against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What Mirtanza ODT is used for

Mirtanza ODT is used in the treatment of depression including relapse prevention.

Depression is longer lasting or more severe than "low moods" everyone has from time to time due to the stress of everyday life. It is thought to be caused by a chemical imbalance in parts of the brain. This affects your whole body and can cause emotional and physical symptoms such as feeling low in spirit, loss of interest in activities, unable to enjoy life, poor appetite or overeating, disturbed sleep, often waking up early, loss of sex drive, lack of energy and feeling guilty over nothing.

This medicine corrects this chemical imbalance and may help relieve the symptoms of depression.

Your doctor, however, may prescribe it for another purpose.

Ask your doctor if you have any questions about why it has been prescribed for you.

This medicine is available only with a doctor's prescription.

Mirtanza ODT is not addictive.

Before You Take Mirtanza ODT

When you must not take it

Do not take Mirtanza ODT:

  • if you are allergic to medicines containing Mirtazapine
  • if you are allergic to any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, wheezing or shortness of breath.

Do not take Mirtanza ODT if you are taking another medicine for depression called a monoamine oxidase inhibitor (MAOI) or have been taking an MAOI within the last 14 days. Taking Mirtanza ODT with an MAOI may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions.

Examples of this type of medicine include phenelzine, tranylcypromine and selegiline.

Ask your doctor or pharmacist if you are not sure if you are or if you have been taking a MAOI medicine.

Do not take Mirtanza ODT if the packaging is torn or shows signs of tampering.

Do not take Mirtanza ODT if the expiry date printed on the pack has passed.

If you are not sure whether you should start taking Mirtanza ODT, talk to your doctor.

Before you start to take it

Do not give Mirtanza ODT to a child or adolescent.

The safety of Mirtanza in patients under 18 years has not been established.

Tell your doctor if:

  1. you are allergic to any other medicines, foods, dyes or preservatives
  2. you are pregnant or plan to become pregnant.
Like most medicines of this kind, Mirtanza ODT is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of taking Mirtanza ODT when pregnant.
  1. you are breastfeeding or wish to breastfeed
It is not known whether Mirtanza ODT passes into breast milk.
  1. If you have or have had any medical conditions, especially the following:
  • Thoughts of suicide or self harm
  • Epilepsy (fits or convulsions)
  • Liver disease such as jaundice
  • Kidney disease
  • Heart disease
  • Low blood pressure
  • Any mental illness (e.g. schitzophrenia, manic depression)
  • Diabetes
  • glaucoma (increased pressure in the eye)
  • problems in urinating due to an enlarged prostate
  • unexplainable high fever, sore throat and mouth ulcers
  • fructose intolerance
  • glucose-galactose malabsorption
  • sucrose-isomaltase insufficiency
  • phenylketonuria

If you have not told your doctor about any of the above, tell them before you take Mirtanza ODT.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by Mirtanza or may affect how well it works. These include:

  • other medicines (eg. SSRIs, venlafaxine, L-tryptophan, nefazodone) for depression, anxiety, obsessive compulsive disorders or pre-menstrual dysphoric disorder
  • Monoamine Oxidase Inhibitors (such as tranylcypromine, phenelzine, and selegiline)
  • medicines containing St. John's Wort (hypericum perforatum)
  • phenytoin or carbamazepine, medicines used to treat epilepsy
  • benzodiazepines, medicines used to treat anxiety and sleeping problems
  • lithium, a medicine used to treat some psychiatric conditions
  • tramadol, a pain killer
  • morphine, a medicine for severe pain
  • cetrizine, a medicine for allergies
  • warfarin, a medicine used to prevent blood clotting.
  • linezolid or erythromycin, both antibiotics
  • rifampicin, a medicine used to treat tuberculosis
  • medicines used to treat fungal infections such as ketoconazole
  • HIV/AIDS medications
  • cimetidine, a medicine used to treat reflux and stomach ulcers
  • triptans such as sumatriptan, naratriptan and zolmitriptan, medicines used to treat migraine
  • medicines that may affect the heart's rhythm such as certain antibiotics and some antipsychotics.

Your doctor will tell you what to do if you are taking any of these medicines.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Mirtanza ODT.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist.

How to take Mirtanza ODT

Follow all directions given to you by your doctor and pharmacist. They may differ from the information contained in this leaflet.

How much to take

Your doctor will tell you how much Mirtanza ODT to take each day. Take exactly the amount your doctor tells you.

The usual starting dose is 15mg per day. Your doctor may slowly increase this dose depending on how you respond to MIRTAZAPINE ODT. The effective dose for most people is usually between 30mg and 45mg per day.

Your doctor may have prescribed a different dose.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

When to take it

Take Mirtanza at about the same time each day.

Your doctor will tell you when to take your tablets.

The tablet(s) should be taken at the same time each day, preferably as a single night-time dose before going to bed; if recommended by your doctor, Mirtanza may be taken in sub-doses equally divided over the day (once in the morning and once at night-time before going to bed).

How to take it

Mirtanza ODT can be taken with or without water.

Please read the following instructions carefully

  • To prevent crushing the tablet, do not push against the tablet pocket (see fig. 1)
  • Each blister contains ten tablet pockets, which are separated by perforations (dotted lines). Bend the strip several times along the dotted lines, and then tear off one tablet pocket (see fig. 2).
  • Carefully peel off the lidding foil, starting in the corner indicated by the arrow (see fig. 3).
  • Take out the tablet with dry hands and place it on the tongue. The tablet will rapidly disintegrate and can be swallowed with or without water (see fig. 4 & 5).

Take the tablet immediately after it is removed from the tablet pocket. Once removed it cannot be stored.

How long to take it

Keep taking Mirtanza ODT until your doctor tells you to stop.

For depression, the length of treatment will depend on how quickly your symptoms improve. Most antidepressants take time to work, so do not be discouraged if you don't feel better right away. Some of your symptoms may improve in 1 to 2 weeks but it can take up to 2 - 4 weeks to feel the full benefit of the medicine.

Even when you feel well, you will usually have to take Mirtanza ODT for 4 to 6 months or even longer to make sure the benefits will last.

If you forget to take it

ONCE DAILY DOSING

If you forget to take the tablet before you go to bed, do not take the missed dose next morning. It may cause drowsiness or sleepiness during the day. Continue treatment in the evening with your normal dose.

TWICE DAILY DOSING

  • Morning dose forgotten – simply take it together with your evening dose
  • Evening dose forgotten – do not take it with the next morning dose. Continue treatment with your normal morning and evening doses.
  • Both doses forgotten – do not try to make up for the missed tablets. Continue with your usual morning and evening dose the next day.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much Mirtanza ODT. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you take too many Mirtanza ODT tablets, you may feel drowsy, dizzy, confused, agitated, have increased heart rate or lose consciousness.

While you are taking Mirtanza ODT

Things you must do

Tell your doctor immediately if you develop fever, chills, sore throat or mouth ulcers or other signs of frequent infections. In rare cases Mirtanza ODT can cause a shortage of white blood cells, resulting in lowering body resistance to infection. These symptoms may appear after 2 - 6 weeks of treatment.

Tell your doctor immediately or go to the nearest hospital for treatment if you have any suicidal thoughts or other mental/mood changes. Occasionally, the symptoms of depression or other psychiatric conditions may include thoughts of harming yourself or committing suicide. Until the full antidepressant effect of your medicine becomes apparent, it is possible these symptoms may increase in the first few weeks of treatment.

If you or someone you know is showing warning signs of suicide- related behaviour while taking Mirtanza ODT, contact your doctor or a mental health professional right away or go to the nearest hospital for treatment.

These signs include:

  • thoughts or talk about death or suicide
  • thoughts or talk of self-harm or harm to others
  • any recent attempts of self-harm
  • Increase in aggressive behaviour, irritability or agitation.

All mentions of suicide or violence must be taken seriously.

Tell your doctor if you become pregnant while taking this medicine. Do not stop taking your tablets until you have spoken to your doctor.

Tell your doctor if for any reason you have not taken your medicine exactly as prescribed. Otherwise your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel the tablets are not helping your condition.

Be sure to keep all your appointments with your doctor so that your progress can be checked. You may need to have blood tests from time to time.

Before starting any new medicine, tell your doctor or pharmacist that you are taking Mirtanza ODT.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Mirtanza ODT.

Things you must not do

Do not drive or operate machinery until you know how Mirtanza ODT affects you. Mirtanza ODT may cause drowsiness, dizziness or sleepiness in some people and affect alertness and concentration. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Do not suddenly stop taking Mirtanza ODT, or lower the dose, without first checking with your doctor.

Do not let yourself run out of medicine over the weekend or on holidays.

Do not stop taking Mirtanza ODT, even if you feel better, unless advised by your doctor. Suddenly stopping Mirtanza ODT may cause nausea, headache, dizziness, anxiety, and agitation.

Your doctor may want you to gradually reduce the amount of Mirtanza ODT you are taking before stopping completely.

Do not use Mirtanza ODT to treat any other conditions unless your doctor tells you to.

Do not give this medicine to anyone else, even if their symptoms seem similar to yours or if they have the same condition as you.

Things to be careful of

Be careful when drinking alcohol while taking Mirtanza ODT. Combining Mirtanza ODT and alcohol can make you more sleepy and less alert. Your doctor may suggest you avoid alcohol while being treated with this medicine.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Mirtanza ODT.

Mirtanza ODT helps most people with depression, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist any questions you may have.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor if you notice any of the following and they bother you:

  • lethargy, drowsiness or sleepiness
  • headache
  • tiredness
  • increase in appetite and weight gain
  • dry mouth
  • nausea, vomiting
  • diarrhoea
  • occasional dizziness or faintness, especially when getting up quickly from a lying or sitting position
  • abnormal sensations in the mouth sensations of numbness in the mouth or swelling in the mouth
  • aggression
  • swollen ankles or feet as a result of fluid accumulation (oedema)
  • rash
  • nightmares/vivid dreams
  • tingling fingers/toes
  • painful joints
  • back pain, muscle aches and pains
  • restless legs
  • abnormal sensation in the skin for example burning, stinging, tickling or tingling
  • urge to move
  • speech disorders
  • difficulty in passing urine (urinary retention)
  • anxiety#
  • insomnia#
    # may be symptoms of depression
  • increased prolactin hormone levels in blood (hyperprolactinaemia, including symptoms such as enlarged breasts and/or milky nipple discharge)
  • sleepwalking
  • prolonged painful erection of the penis

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • suicidal ideation or behaviour
  • epileptic attack (seizures)
  • shaking or tremors
  • sudden muscle contractions (myoclonus)
  • attack of excessive excitability (mania)
  • agitation
  • confusion
  • hallucinations
  • yellow colouring of eyes or skin; this may suggest disturbance in liver function
  • generalised fluid retention with weight gain
  • skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty breathing
  • fever, sore throat, mouth ulcers, gastrointestinal (stomach, bowels) disturbances and other signs of infection
  • fever, sweating, increased heart rate, diarrhoea, (uncontrollable) muscle contractions, shivering, overactive reflexes, restlessness, mood changes and unconsciousness (serotonin syndrome)
  • muscle pain, stiffness and/or weakness, darkening or discolouration of the urine (rhabdomyolysis)

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Ask your doctor or pharmacist if you don't understand anything in this list.

After taking Mirtanza ODT

Storage

Keep your tablets in the blister pack until it is time to take them. The tablets will not keep if you take them out of their blister.

Store below 30 degrees Celsius.

Do not store Mirtanza ODT or any other medicine in the bathroom or near a sink.

Do not leave Mirtanza ODT in the car or on window sills. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one and a half meters above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Mirtanza ODT, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Mirtanza ODT 15, 30 and 45 mg tablets are presented in a blister pack of 30 or 90 tablets*.
*not marketed

MIRTANZA ODT 15 mg
White, round tablets debossed with ‘36’ on one side and ‘A’ on the other side with an embossed circular edge.

MIRTANZA ODT 30 mg
White, round tablets debossed with ‘37’ on one side and ‘A’ on the other side with an embossed circular edge.

MIRTANZA ODT 45 mg
White, round tablets debossed with ‘38’ on one side and ‘A’ on the other side with an embossed circular edge.

Ingredients

Active Ingredient:

Mirtazapine

Contains Aspartame

Other Ingredients:

  • Crospovidone
  • Mannitol
  • Microcrystalline cellulose
  • Aspartame*
  • Colloidal anhydrous silica
  • Magnesium stearate
  • Strawberry Guarana 586997 AP0551
  • (HF82) N&A Peppermint FL SD # 517

Please read this leaflet carefully before you start taking Mirtanza ODT. You may wish to keep it to read again.

AUST Rs

15 mg: Aust R 183404

30 mg”: Aust R 183405

45 mg: Aust R 183406

Name and Address of the Sponsor

Arrow Pharma Pty Ltd
15-17 Chapel St
Cremorne
VIC 3121

Australia

Ph: 1800 195 055

Date of Preparation

May 2020

Published by MIMS July 2020

BRAND INFORMATION

Brand name

Mirtanza ODT

Active ingredient

Mirtazapine

Schedule

S4

 

1 Name of Medicine

Mirtazapine.

6.7 Physicochemical Properties

Mirtazapine is a tetracyclic piperazinoazepine analogue of mianserin, a chemical structure unrelated to tricyclic antidepressants, monoamine oxidase inhibitors or selective serotonin reuptake inhibitors. Mirtazapine is a white or almost white powder, slightly hygroscopic to hygroscopic. It is freely soluble in anhydrous ethanol and practically insoluble in water.

Chemical structure.

Active substance: Mirtazapine.
Chemical name: (14bRS)-2-methyl-1,2,3,4,10,14b-hexahydropyrazino [2,1-a] pyrido [2,3-c][2] benzazepine.
Molecular formula: C17H19N3.
Molecular weight: 265.4.

CAS number.

61337-67-5.

2 Qualitative and Quantitative Composition

Each Mirtanza ODT 15, 30 and 45 orally disintegrating tablet contains 15, 30 and 45 mg mirtazapine respectively.

Excipients with known effect.

Aspartame.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Mirtanza ODT 15 mg.

White, round tablets debossed with '36' on one side and 'A' on the other side with an embossed circular edge.

Mirtanza ODT 30 mg.

White, round tablets debossed with '37' on one side and 'A' on the other side with an embossed circular edge.

Mirtanza ODT 45 mg.

White, round tablets debossed with '38' on one side and 'A' on the other side with an embossed circular edge.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Mirtazapine is an antidepressant, which can be given as treatment for episodes of major depression. Mirtazapine is an antagonist of central α2-auto and heteroadrenoceptors which causes an increase in both noradrenaline and serotonin release. The effect of released serotonin is exerted specifically via 5-HT1 type receptors, because 5-HT2 and 5-HT3 type receptors are specifically blocked by mirtazapine. Mirtazapine is accordingly a noradrenergic and specific serotonergic antidepressant. The α2, 5-HT2 and 5-HT3 antagonistic effects all contribute to the antidepressant profile of mirtazapine. The presentation of mirtazapine is as a racemate. The two enantiomers contribute differently to its pharmacological profile. The α2 and 5-HT2 receptor blocking activity is contained in the (S)+ enantiomer, whereas the 5-HT3 receptor blocking activity is contained in the (R)-enantiomer. The presence of both enantiomers is therefore considered to be essential for the antidepressant activity of mirtazapine. In one study, there was no efficacy difference indicated between the two enantiomers, despite their different receptor affinities.
Mirtazapine is generally well tolerated. The histamine H1-antagonistic activity of mirtazapine may cause a degree of sedation in the first weeks of treatment. It has practically no anticholinergic activity.
Mirtazapine has been associated with acute postural hypotension in healthy volunteer studies but this occurred rarely in patient studies (see Section 4.8 Adverse Effects (Undesirable Effects)).

Clinical trials.

Several placebo controlled double blind studies have demonstrated that mirtazapine is statistically significantly more effective than placebo in the short-term treatment of a major depressive episode; the efficacy is maintained during continuation treatment with mirtazapine.

Active controlled studies.

The efficacy of mirtazapine has been found to be comparable to several standard antidepressant agents (amitriptyline, doxepin, clomipramine). In addition, eleven 6 or 8 week studies and a 24 week study have been performed in moderately to severely depressed patients in which efficacy and tolerability of mirtazapine were compared to SSRIs (4 vs fluoxetine, 3 vs paroxetine, 2 vs sertraline, 2 vs fluvoxamine and 1 vs citalopram). The primary efficacy parameters in these studies were:
change from baseline on HAM-D total score (Hamilton depression rating scale, 17 items). 7 studies;
proportion or number of HAM-D 50% responders, 3 studies;
change from baseline on MADRAS total score (Montgomery-Asberg depression rating scale, 10 items), 1 study;
VAMRS 6 items (Visual Analogue Mood Rating Scale), 1 study. Change in HAM-D (12 items) total score was a secondary parameter in this study.
On an intention to treat basis, a total of 1402 patients were treated with mirtazapine and 1405 patients were treated with the comparator. In all 12 studies, mirtazapine proved to be at least comparable in efficacy to the SSRIs. In 11 of these studies, statistically significant greater reductions in HAM-D or MADRS total scores and more responders were observed in the mirtazapine groups at one or more timepoints in the first 4 weeks.
A meta-analysis of these 12 studies provides further comparison of the onset of efficacy of mirtazapine relative to the SSRIs studied. The primary efficacy parameter for this meta-analysis was time to first 50% reduction on recalculated HAM-D total score (17 items) or recalculated MADRS total score (10 items). There were also a number of secondary parameters which are identified in Tables 2 and 3. Table 2 provides an analysis of the relative event rates (estimated hazard ratios) for various depression parameters limited to the first 3 treatment weeks for the occurrence of the event and the entire 6-8 week study period to define whether the event was sustained or not. The increased hazard ratios demonstrate that the probability at any time t of first response (50% or more score reduction), remission, sustained response or sustained remission was consistently and significantly greater among mirtazapine treated than SSRI treated patients, indicating an earlier onset of efficacy. The statistically earlier onset of action observed with mirtazapine may not necessarily translate in to a meaningful clinical benefit for an individual patient. Table 3 presents the proportions of HAM-D responders and HAM-D/MADRS remitters at the various time points during treatment. At most time points there were significantly more responders and remitters among mirtazapine treated patients than among SSRI treated patients.
Some secondary parameter results have been excluded from Table 3. These were number of: 50% Bech responders; 50% HAM-D factor I anxiety/ somatisation responders; 50% HAM-D factor V retardation responders; 50% HAM-D factor VI sleep disturbance responders; HAM-D item depressed mood responders (= 0 or < 2); HAM-D item suicide or MADRS item suicidal thoughts (= 0 or < 2).
Statistically significant differences favouring mirtazapine were observed for HAM-D factors V and VI at week 1 to 6 timepoints. Statistically significant differences favouring mirtazapine were observed for HAM-D factor I at week 1 to 4 timepoints. A statistically significant difference was observed in favour of mirtazapine for Bech responders at the week 2 timepoint. There were no other statistically significant differences.
An eight week comparative study was performed to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of 157 hospitalised patients with severe depression with melancholic features (HAM-D total score > 25). In this study, mirtazapine and venlafaxine were equally effective in reducing symptoms of depression and improving quality of life during treatment.

Long-term maintenance of efficacy and relapse prevention.

The long-term maintenance of antidepressant efficacy of mirtazapine was originally established in three active controlled and active/ placebo controlled studies with treatment periods up to 24 months (amitriptyline as active). Long-term maintenance of efficacy was also confirmed in extension phases of 3 SSRI comparator studies, a 24 week paroxetine comparator study and 1 venlafaxine comparator study. Additionally, a multicentre, long-term, double blind, placebo controlled study of relapse prevention in male and female outpatients diagnosed with moderate to severe recurrent major depression (protocol 003041) was performed. In the initial open label phase of the study, 421 patients were treated with mirtazapine for 8-12 weeks. Patients remitting after 8-12 weeks were randomised into the 40 week, double blind, relapse prevention phase of the study. The remitted patients were randomised to either mirtazapine at the final titrated dose they received during the open label phase or placebo (79 to mirtazapine and 81 to placebo). The results of the trial showed that mirtazapine reduced the risk of relapse by more than half (15/76 = 19.7% relapsed on mirtazapine versus 35/80 = 43.8% relapsed on placebo, p = 0.001). The treatment was well tolerated with dropouts due to adverse events being 11.4% (9/79) from the mirtazapine group and 2.5% (2/81) from the placebo group. Further discontinuation details are summarised in Table 4.

Elderly.

The efficacy and tolerability in elderly patients was investigated in three randomised controlled trials. In two six week trials with a total of 270 patients aged over 55 years (mean age 70 and 62 years respectively), mirtazapine was at least as effective as amitriptyline and all treatments were well tolerated. In an eight week study in 255 patients aged 65 and over (mean age 72 years) comparing mirtazapine with paroxetine, mean HAM-D scores were similar at endpoint but lower for mirtazapine in the first 3 weeks, although only at day 14 was the difference statistically significant. Total discontinuation rates were similar (22.7% for mirtazapine versus 31.0% for paroxetine), although discontinuation due to adverse events was lower with mirtazapine than paroxetine (14.8% versus 26.2%) and discontinuation due to lack of efficacy higher (3.9% versus 0%).

5.2 Pharmacokinetic Properties

Absorption.

After oral administration of mirtazapine tablets, the active substance mirtazapine is rapidly and well absorbed (bioavailability ≈ 50%), reaching peak plasma levels after about 2 hours. Food intake has no clinically significant influence on the pharmacokinetics of mirtazapine.

Distribution.

Binding of mirtazapine to plasma proteins is approx. 85%. The half-life of elimination ranged from 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded and shorter half-lives have been seen in young men. The half-life of elimination is sufficient to justify once a day dosing. Steady state is reached after 3-6 days, after which there is no further accumulation. Mirtazapine displays linear pharmacokinetics within the recommended dose range.

Metabolism.

In vitro data from human liver microsomes indicate that cytochrome P450 enzymes CYP 2D6 and CYP 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP 3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites.
The presentation of mirtazapine is as a racemate. It is not known whether first pass extraction of the drug is stereoselective but it is known that the clearance of the two enantiomers is by different metabolic processes.

Excretion.

Mirtazapine is extensively metabolized and its metabolites are eliminated via the urine and faeces within four days. Major pathways of biotransformation are demethylation and oxidation, followed by conjugation. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.

Special populations.

Renal and/or hepatic impairment.

The clearance of mirtazapine may be decreased as a result of renal or hepatic insufficiency. Mirtazapine is substantially excreted by the kidney (75%) and the risk of decreased clearance of this drug is greater in patients with impaired renal function (see Section 4.2 Dose and Method of Administration).

Geriatric.

The recommended dosage regimen is the same as for adults. Increases should be monitored carefully, (see Section 4.2 Dose and Method of Administration).

Children and adolescents.

The safety and effectiveness of mirtazapine has not been established in children and adolescents and therefore should not be prescribed in these patient groups, (see Section 4.4 Special Warnings and Precautions for Use).

Sex.

The half-life of elimination of mirtazapine ranged from 20-40 hours, longer half-lives up to 65 hours have occasionally been recorded and shorter half-lives have been seen in young men.

Race.

There is no information available regarding the effect of race on the pharmacokinetics of mirtazapine.

5.3 Preclinical Safety Data

Genotoxicity.

Mirtazapine was not genotoxic in a series of tests for gene mutation and chromosomal and DNA damage.

Carcinogenicity.

An eighteen month carcinogenicity study in mice showed an increase in the development of hepatic tumours in males after mirtazapine treatment at oral doses of 20 mg/kg/day and above. In a two year carcinogenicity study in rats, oral doses of mirtazapine greater than 20 mg/kg/day were associated in males with an increased incidence of thyroid follicular cell adenomas and carcinomas.
Since the only tumours found in carcinogenicity studies with mice and rats were considered to be species specific, nongenotoxic responses associated with long-term treatment with hepatic enzyme inducers, mirtazapine is not expected to possess carcinogenic potential at therapeutic dosages in the clinic.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of major depression including relapse prevention.

4.3 Contraindications

Hypersensitivity to mirtazapine or to any of the excipients.
MAO inhibitors as concomitant therapy. It is recommended that mirtazapine not be used in combination with MAO inhibitors, or within 14 days of initiating or discontinuing therapy with a MAO inhibitor (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Clinical worsening and suicide risk.

The risk of suicidality (suicidal ideation and suicidal behaviours) is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients. Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and/or behaviours whether or not they are taking antidepressant medication, and this risk may persist until significant remission occurs. Suicide is a known risk in depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms. Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation or behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Patients with comorbid depression associated with other psychiatric disorders being treated with antidepressants should be similarly observed for clinical worsening and suicidality.
Pooled analysis of short-term placebo controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increased the risk of suicidal ideation and/or behaviours in children, adolescents, and young adults (aged 18-24 years) with major depressive disorder (MDD) and other psychiatric disorders during the initial treatment (generally the first one to two months). Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond the age of 24 years; there was a reduction with antidepressants compared to placebo in adults aged 65 years and older.
The pooled analyses of placebo controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials (4 to 16 weeks) of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in the risk of suicidality among drugs, but a tendency towards an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across different indications, with the highest incidence in MDD trials. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications.
No suicides occurred in any of the paediatric trials. There were few suicides in the adult trials, but the number was not sufficient to reach any conclusion about the effect of antidepressants on suicide. It is unknown whether suicidality risk extends to longer-term use, i.e. beyond several months. However, there is substantial evidence from placebo controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
Symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adults, adolescents and children being treated with antidepressants for major depressive disorders as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidality has not been established, there is concern that such symptoms may be precursors of emerging suicidality.
Families and caregivers of children and adolescents being treated with antidepressants for MDD or for any other conditions (psychiatric or nonpsychiatric) should be informed about the need to monitor these patients for the emergence of agitation, irritability, unusual changes in behaviour, and other symptoms described above, as well as the emergence of suicidality and to report such symptoms immediately to health care providers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
Prescriptions for mirtazapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Conditions which need supervision.

Careful dosing as well as regular and close monitoring is necessary in patients with:

Hepatic impairment.


Epilepsy and organic brain syndrome.

(See Section 4.8 Adverse Effects (Undesirable Effects)). Mirtazapine should be introduced cautiously in patients who have a history of seizures. Treatment should be discontinued in any patient who develops seizures, or where there is an increase in seizure frequency.

Renal impairment.

Mirtazapine is substantially excreted by the kidney (75%) and the risk of decreased clearance of this drug is greater in patients with impaired renal function.

Cardiac diseases.

Such as conduction disturbances, angina pectoris and recent myocardial infarct, where normal precautions should be taken and concomitant medicines carefully administered.

Low blood pressure and conditions that would predispose patients to hypotension.

(Dehydration, hypovolemia and treatment with antihypertensive medication.)

Diabetes mellitus.

In patients with diabetes, antidepressants may alter glycemic control. Insulin and/or oral hypoglycemic dosage may need to be adjusted and close monitoring is recommended.
Like with other antidepressants, the following should be taken into account.
As for antidepressants in general care should be taken in patients with:
Worsening of psychotic symptoms can occur when antidepressants are administered to patients with schizophrenia or other psychotic disturbances; paranoid thoughts can be intensified.
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone can increase the likelihood of precipitation of a mixed/ manic episode in patients at risk of bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder and depression. When the depressive phase of the bipolar disorder is being treated, it can transform into the manic phase. Patients with a history of mania/ hypomania should be closely monitored. Mirtazapine should be discontinued in any patient entering a manic phase.
Care should be taken in patients with micturition disturbances like prostate hypertrophy (although problems are not to be expected because mirtazapine possesses only very weak anticholinergic activity).
Acute narrow angle glaucoma and increased intraocular pressure (however mirtazapine has weak anticholinergic activity).
Akathisia/ psychomotor restlessness: the use of antidepressants have been associated with the development of akathisia, characterized by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Mirtazapine is not addictive. Postmarketing experience shows that abrupt termination of treatment after long-term administration may sometimes result in withdrawal symptoms. The majority of withdrawal reactions are mild and self limiting. Among the various reported withdrawal symptoms, dizziness, agitation, anxiety, headache and nausea are the most frequently reported. Even though they have been reported as withdrawal symptoms, it should be realised that these symptoms may be related to underlying disease. As advised see Section 4.2 Dose and Method of Administration, it is recommended to discontinue treatment with mirtazapine gradually.

Jaundice.

Treatment should be discontinued if jaundice occurs.

Hyponatremia.

Hyponatremia has been reported very rarely with the use of mirtazapine. Caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatremia.

Serotonin syndrome.

Development of serotonin syndrome may occur in association with treatment with SSRIs and SNRIs, particularly when given in combination with MAOIs (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions) or other serotonergic agents (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Symptoms and signs of serotonin syndrome include rapid onset of neuromuscular excitation (hyper-reflexia, incoordination, myoclonus, tremor), altered mental status (confusion, agitation, hypomania) and autonomic dysfunction (diaphoresis, diarrhoea, fever, shivering and rapidly fluctuating vital signs). Treatment with mirtazapine should be discontinued if such events occur and supportive symptomatic treatment initiated. From postmarketing experience it appears that serotonin syndrome occurs very rarely in patients treated with mirtazapine alone (see Section 4.8 Adverse Effects (Undesirable Effects)).

Phenylketonurics.

Phenylketonurics should be informed Mirtanza ODT contains aspartame, a source of phenylalanine. Each tablet with 15 mg, 30 mg and 45 mg, corresponds to 1.5 mg, 3.0 mg and 4.5 mg phenylalanine respectively. It may be harmful for patients with phenylketonuria.
Mirtazapine OD contains sugar spheres containing sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Neutropenia, agranulocytosis.

Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis, has been reported during treatment with mirtazapine. The symptoms mostly appear after 2-6 weeks of treatment. The bone marrow depression is, in general, reversible after termination of treatment. However in very rare cases agranulocytosis can be fatal. Reversible agranulocytosis has been reported as a rare occurrence in clinical studies with mirtazapine. In the postmarketing period with mirtazapine very rare cases of agranulocytosis have been reported, mostly reversible, but in some cases fatal. All fatal cases concerned patients over 65 years. Postmarketing data indicate that the rate of occurrence of agranulocytosis and agranulocytosis-like disorders (whether or not causally related) amongst mirtazapine users is no greater than that in the background population. One should be alert for symptoms like fever, sore throat, stomatitis or other signs of infections. If such symptoms occur the treatment should be stopped and blood counts taken.

Use in the elderly.

Elderly patients are often more sensitive, especially with regard to the undesirable effects of antidepressants. During clinical research with mirtazapine, undesirable effects have not been reported more often in elderly patients than in other age groups (see Section 5.1, Clinical trials; Section 4.2 Dose and Method of Administration).

Use in renal impairment.

See Conditions which need supervision, above; see Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties, Special populations, Renal and/or hepatic impairment.

Paediatric use.

Mirtazapine should not be used to treat children or adolescents under the age of 18 years. Suicide related behaviors (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behavior and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken; the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioral development are lacking.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacokinetic interactions.

Mirtazapine is extensively metabolised by CYP2D6 (resulting in the 8-hydroxy metabolite) and CYP3A4 (N-demethyl and N-oxide metabolites) and to a lesser extent by CYP1A2. An interaction study with healthy volunteers showed no influence of paroxetine, a CYP2D6 inhibitor, on mirtazapine pharmacokinetics in steady state.
Coadministration of the potent inhibitor of CYP3A4, ketoconazole, in healthy male volunteers increased mirtazapine peak plasma concentration levels and AUC by approximately 40% and 50% respectively.
When cimetidine (weak inhibitor of CYP1A2, CYP2D6 and CYP3A4) is administered with mirtazapine, the mean plasma concentration of mirtazapine may increase more than 50%. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started or increased when cimetidine treatment is ended. Caution should be exercised and the dose may have to be decreased when coadministering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, ketoconazole, erythromycin, cimetidine or nefazodone.
Carbamazepine and phenytoin, inducers of CYP3A4, increased mirtazapine clearance about twofold, resulting in a decrease in mirtazapine plasma levels of 45-60%. When carbamazepine, phenytoin or another inducer of drug metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with an inducer is stopped, mirtazapine dose may have to be decreased.
In in vivo interaction studies, mirtazapine did not influence the pharmacokinetics of paroxetine (CYP2D6 substrates), carbamazepine or phenytoin (CYP3A4 inducers), amitryptyline or cimetidine.
In a mirtazapine and lithium interaction study, the steady-state pharmacokinetics of lithium were not affected by coadministration of a single oral dose of 30 mg of mirtazapine. Correspondingly, the single dose pharmacokinetics of mirtazapine were not affected by the lithium steady-state.

Pharmacodynamic interactions.

Mirtazapine should not be administered concomitantly with MAO inhibitors or within two weeks after discontinuation of MAO inhibitor therapy. In the opposite way about two weeks should pass before patients treated with mirtazapine should be treated with MAO inhibitors (see Section 4.3 Contraindications). In addition, as with SSRIs, coadministration with other serotonergic active substances (L-tryptophan, triptans, tramadol, linezolid, SSRIs, venlafaxine, lithium and St John's wort, Hypericum perforatum, preparations) may lead to an incidence of serotonin associated effects (see Section 4.4 Special Warnings and Precautions for Use). Caution should be advised and a closer clinical monitoring is required when these active substances are combined with mirtazapine.
Mirtazapine may potentiate the sedative effects of benzodiazepines and other sedatives (especially antipsychotics, antihistamine H1-antagonists, opioids). Caution should be taken when these drugs are prescribed together with mirtazapine.
Mirtazapine may potentiate the central nervous dampening action of alcohol; patients using mirtazapine should therefore be advised to avoid alcohol during tasks which require concentration and alertness.
Mirtazapine dosed at 30 mg daily caused a small but statistically significant increase of the INR in subjects treated with warfarin. Both at continuing stable doses and higher doses of mirtazapine, a more pronounced effect cannot be excluded. It is advisable to monitor the prothrombin time more carefully in case of concomitant treatment of warfarin with mirtazapine.
From postmarketing experience it appears that serotonin syndrome occurs very rarely in patients treated with mirtazapine in combination with SSRIs or venlafaxine. If the combination is considered therapeutically necessary, dosage changes should be made with caution and there should be adequate close monitoring for early signs of serotonergic overstimulation.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a fertility study in rats, mirtazapine was given at doses up to 100 mg/kg [ca. 20 times the recommended human dose of 45 mg on a mg/m2 basis]. The drug did not affect mating and conception, but oestrus cycling was disrupted at doses that were 3 or more times the recommended human dose of 45 mg on a mg/m2 basis.
(Category B3)
There are insufficient clinical data to assess the possible effect of mirtazapine on pregnancy.
Oral dosing of pregnant rats with mirtazapine at 100 mg/kg/day was associated with a reduction in survival of the offspring, and an increased incidence of postnatal mortality. Mirtazapine was not teratogenic in rats at these dose levels, or in rabbits at oral doses up to 40 mg/kg/day.
Although studies in animals have not shown any teratogenic effects of toxicological significance the safety of mirtazapine in human pregnancy has not been established. Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN to mirtazapine treatment, this potential risk cannot be ruled out taking into account the related mechanism of action (increase in serotonin concentrations). Mirtazapine should be used during pregnancy only if it is clearly needed. Women of childbearing potential should employ an adequate method of contraception if taking mirtazapine.
Australian categorisation definition of Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.
Although animal experiments show that mirtazapine is excreted only in very small amounts in the milk, postnatal mortality was increased when lactating rats were given mirtazapine orally at 100 mg/kg/day. The use of mirtazapine in breastfeeding mothers is not recommended since no human data in breast milk are available.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Depressed patients display a number of symptoms that are associated with the illness itself. It is therefore sometimes difficult to ascertain which symptoms are a result of the illness itself and which are a result of treatment with mirtazapine. See Table 1.

Postmarketing reports.

Skin and subcutaneous tissue disorders.

Stevens-Johnson syndrome, dermatitis bullous, erythema multiforme, toxic epidermal necrolysis, rash (including erythematous and maculopapular), rare cases of increased sweating, alopecia, pruritus and urticaria.

Musculoskeletal connective tissue and bone disorders.

Back pain, arthralgia, myalgia, rhabdomyolysis.

Nervous system disorders.

Lethargy, dysarthria, serotonin syndrome, somnolence (i.e. drowsiness, sedation), impaired concentration, dizziness, paraesthesia, headache, hyperkinesia, rare cases of cerebrovascular disorder, convulsions, tremor and myoclonus, movement disorders**. Very rare cases of oral paraesthesia.

Psychiatric disorders.

Suicidal ideation***, suicidal behaviour***, confusion, agitation, aggression, paroniria, less common or rare occurrences of; nightmares/ vivid dreams, hallucination, mania, depression, anxiety*, insomnia* and psychomotor restlessness** and somnambulism.

Gastrointestinal disorders

Constipation, vomiting, pancreatitis, increased salivation, nausea, diarrhoea, dry mouth, less common or rare cases of stomatitis, very rare cases of oral hypoaesthesia and mouth oedema.

Hepatobiliary disorders.

Hepatic function abnormal, elevated hepatic enzymes or transaminases, rare cases of jaundice, hepatitis.

Metabolism and nutrition disorders.

Hyponatraemia, increased appetite, rare cases of hypercholesterolaemia, hyperlipidaemia.

Cardiac disorders.

Tachycardia, palpitations, rare; arrhythmia, myocardial infarction, chest pain.

Vascular disorders.

Hypotension, dependent oedema, hypertension, orthostatic hypotension, rare cases of thromboembolic disorder, pulmonary embolism.

Blood and lymphatic system disorders.

Leukopenia, granulocytopoenia, rare cases of agranulocytosis, (see Section 4.4 Special Warnings and Precautions for Use), rare cases of; thrombocytopenia, pancytopenia, anaemia, aplastic anaemia, eosinophilia and coagulation disorder.

Endocrine disorders.

Hyperprolactinaemia (and related symptoms e.g. galactorrhea and gynaecomastia).

Renal and urinary disorders.

Rare cases of urinary retention.

Reproductive system and breast disorders.

Priapism.

General disorders and administration site conditions.

Oedema including generalised, peripheral and face oedema; fatigue/ asthenia, rare cases of pyrexia, syncope, chest pain and drug withdrawal symptoms.

Investigations.

Increases in gamma-glutamyltransferase levels, hypertriglyceridaemia, weight gain, increased creatine kinase.

Eye disorders.

Very rare cases of glaucoma.
* Upon treatment with antidepressants in general, anxiety and insomnia (which may be symptoms of depression) can develop or become aggravated. Under mirtazapine treatment, development or aggravation of anxiety and insomnia has been reported very rarely.
** Including akathisia, hyperkinesia.
*** Cases of suicidal ideation and suicidal behaviours have been reported during mirtazapine therapy or early after treatment discontinuation (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

To prevent crushing of the tablet, do not push against a tablet pocket. Each strip has 10 tablets separated by perforations. Bend the strip several times along a perforation, then tear off one tablet pocket. Carefully peel off the lidding foil, starting in the corner indicated by the arrow. Take out the tablet with dry hands and place it on the tongue, where it will rapidly disintegrate and can be swallowed with or without water.

Adults.

Treatment should begin with 15 mg daily. The dosage generally needs to be increased to obtain an optimal clinical response. The effective daily dose is usually between 30 and 45 mg, but responses have been observed at 60 mg per day.

Elderly.

The recommended dose is the same as that for adults. In elderly patients an increase in dosing should be done under close supervision to elicit a satisfactory and safe response.
The tablet should be used immediately after removal from its pocket; it cannot be stored.
The clearance of mirtazapine may be decreased in patients with renal or hepatic insufficiency. This should be taken into account when prescribing mirtazapine to this category of patients (see Section 5.2 Pharmacokinetic Properties).
Mirtazapine has a half-life of 20-40 hours and therefore mirtazapine is suitable for once a day administration. It should be taken preferably as a single night time dose before going to bed. Mirtazapine may also be given in subdoses equally divided over the day (once in the morning and once at night time).
Treatment should preferably be continued until the patient has been completely symptom free for 4-6 months. After this, treatment can be gradually discontinued to avoid withdrawal symptoms (see Section 4.4 Special Warnings and Precautions for Use). Mirtazapine begins to exert its effect in general after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response within 2-4 weeks. With an insufficient response, the dose can be increased up to the maximum dose. If there is no response within a further 2-4 weeks, then treatment should be stopped.

Children and adolescents (< 18 years of age).

In placebo controlled trials, safety and efficacy of mirtazapine in the treatment of children and adolescents under the age of 18 years with major depressive disorder have not been established. Safety and efficacy in this population cannot be extrapolated from adult data. Therefore mirtazapine should not be used in children and adolescents under the age of 18 years.

4.7 Effects on Ability to Drive and Use Machines

Mirtazapine may impair concentration and alertness (more commonly in the initial phase of treatment). Patients treated with mirtazapine should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the treatment does not affect them adversely.

4.9 Overdose

Postmarketing experience concerning overdose with mirtazapine alone indicates that symptoms are usually mild. The symptoms of overdose are an exaggeration of the pharmacological action of mirtazapine and may include symptoms such as dizziness, impaired consciousness (confusion, disorientation, stupor, coma), agitation, tremor, tachycardia and hyper and hypotension. As with all overdose attempts, the possibility of multiple drug ingestion should be borne in mind. As with antidepressants in general, serious outcomes, including fatalities, are possible at dosages much higher than the therapeutic dose, especially with mixed overdoses.

Overdose management.

Cases of overdose should receive appropriate symptomatic and supportive therapy for vital functions.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription only medicine).

6 Pharmaceutical Particulars

6.1 List of Excipients

Mirtanza ODT tablets contain the following inactive ingredients: crospovidone, mannitol, microcrystalline cellulose, aspartame, colloidal anhydrous silica, magnesium stearate, Strawberry Guarana 586997 AP0551 and (HF82) N and A Peppermint FL SD #517.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Mirtanza ODT 15, 30 and 45 (15, 30 and 45 mg mirtazapine) are presented in pack sizes of 30 and 90* tablets in PA/Alu/PVC-Peelable lidding foil blister strips. Each blister strip contains 10 tablets.
* Not marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes