Consumer medicine information

Lumin

Mianserin hydrochloride

BRAND INFORMATION

Brand name

Lumin

Active ingredient

Mianserin hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lumin.

What is in this leaflet

This leaflet answers some common questions about Lumin.

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 Lumin against the benefits expected 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 Lumin is used for

Lumin is used to treat depression.

Lumin is an antidepressant, which works by acting on chemicals in your brain called amines. These amines are involved in controlling mood.

Ask your doctor if you have any questions about why Lumin has been prescribed for you. Your doctor may have prescribed Lumin for another reason.

Lumin is not approved for use in children and adolescents below 18 years of age for the treatment of depression or other mental disorders.

The safe use and effectiveness of Lumin in treating these disorders, for this age group, has not been established.

Lumin is available only with a doctor's prescription.

Before you take Lumin

When you must not take it

Do not take Lumin if you are allergic to:

  • medicines containing mianserin hydrochloride (e.g. Tolvon)
  • 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, mouth, throat or other parts of the body, shortness of breath, wheezing or troubled breathing.

Check with your doctor or pharmacist if you are not sure about any of the above.

Do not take Lumin if you:

  • suffer from mania, a mental condition characterised by episodes of overactivity, elation or irritability.
  • have severe liver disease

Do not take Lumin 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. If you stop taking Lumin, do not take MAOI during the next 2 weeks either. Taking Lumin with an MAOI may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions.

Ask your doctor or pharmacist if you are not sure if you are taking, or have been taking a MAOI. MAOIs are medicines used to treat depression and symptoms of Parkinson's disease. Examples of MAOIs are phenelzine (Nardil), tranylcypromine (Parnate), moclobemide (e.g. Aurorix, Arima), selegiline (Eldepryl, Selgene) and linezolid (Zyvox).

Do not take Lumin if the packaging shows signs of tampering or the tablets do not look quite right.

Do not take Lumin if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date, it may not work as well.

Talk to your doctor if you are not sure whether you should start taking this medicine.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking Lumin during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. It is not known whether Lumin passes into breast milk.

Your doctor will discuss the risks and benefits of taking Lumin when breastfeeding.

Tell your doctor if you have or have had any of the following medical conditions:

  • blood pressure problems
  • heart disease, including certain kinds of heart conditions that change your heart rhythm, a recent heart attack, heart failure, or taking certain medicines known to change heart rhythm
  • liver problems (e.g. jaundice)
  • kidney problems
  • any mental illness other than depression
  • epilepsy, (fits or convulsions)
  • diabetes
  • glaucoma, (increased pressure in the eye)
  • problems with urinating due to an enlarged prostate.
  • Mental illness such as schizophrenia and manic depression (alternating periods of elation/overactivity and depressed mood).

If you have not told your doctor about any of the above, tell him/her before you start taking Lumin.

Taking other medicines

Do not take Lumin if you are taking any monoamine oxidase inhibitor (MAOI) such as:

  • phenelzine (Nardil) and tranylcypromine (Parnate), moclobemide (eg. Aurorix, Arima), used to treat depression
  • selegiline (Eldepryl, Selgene), used to treat symptoms of Parkinson's disease.

Wait at least 14 days after stopping your MAOI before starting Lumin.

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

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

  • other medicines for depression
  • Monoamine Oxidase Inhibitors (MAOIs)
  • medicines used to treat epilepsy such as barbiturates, carbamazepine and phenytoin
  • medicines used to treat high blood pressure
  • oral antidiabetic medicines or insulin
  • medicines used to prevent blood clots, such as warfarin.
  • medicines that may affect the heart rhythm such as certain antibiotics and some anti-psychotics.

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

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Lumin.

How to take Lumin

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

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

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

The dose varies from patient to patient.

Your doctor will decide the right dose for you. This depends on your condition, age, whether or not you are taking any other medicines, and how you respond to Lumin.

Lumin is usually started at a low dose, at 30mg per day. This may be given as a single night-time dose before going to bed or given in three divided doses. Your doctor may slowly increase this dose depending on how you respond to Lumin. The effective dose for most people is usually between 30mg and 90mg per day.

Elderly:
The usual starting dose will not be more than 30mg per day. Your doctor may slowly increase or decrease your dose, depending on how you respond to Lumin.

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How to take it

Swallow the tablets whole with a glass of water. Do not chew the tablets.

When to take it

Lumin should be taken between meals.

Lumin can be taken as a single dose (eg. at bedtime) or as divided doses (eg. three times a day). Your doctor will advise you.

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it for

Keep taking Lumin for as long as your doctor recommends. The length of treatment will depend on how quickly your symptoms improve.

Most medicines for depression take time to work, so do not be discouraged if you do not feel better right away. Some of your symptoms may improve in 1 or 2 weeks but it can take up to 4 or 6 weeks to feel the full benefit of Lumin.

Even when you feel well, you will usually have to take Lumin for several months or longer, to make sure the benefits will last.

If you forget to take it

IF YOU TAKE ONE DOSE A DAY AT BEDTIME:

If you forget to take Lumin before you go to bed and you wake up late in the night or early in the morning, do not take any Lumin until you have checked with your doctor. You may have difficulty waking up or experience drowsiness in the morning or during the day, if you take Lumin at these times.

IF YOU TAKE MORE THAN ONE DOSE A DAY:

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

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 Lumin.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Lumin, you may feel drowsy, dizzy and lightheaded, have changes in heart rate (fast, slow or irregular), and/or fainting which could be symptoms of a life-threatening condition known as Torsades de Pointes. You may also have fits and problems breathing.

Keep Lumin out of the reach of children. Children are much more sensitive than adults to medicines such as Lumin. An accidental overdose is especially dangerous.

While you are taking Lumin

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Lumin.

Tell all the doctors, dentists and pharmacists who treat you that you are taking this medicine.

Tell your doctor immediately 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. These symptoms may continue or get worse during the first one to two months of treatment until the full antidepressant effect of the medicine becomes apparent.

Information from clinical trials have shown an increased risk of suicidal behaviour in young adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

Contact your doctor or a mental health professional right away or go to the nearest hospital for treatment if you or someone you know is showing any of the following warning signs of suicide:

  • worsening of your depression
  • thoughts or talk of 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 any other unusual changes in behaviour or mood.

All mentions of suicide or violence must be taken seriously.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

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 Lumin is not helping your condition.

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

Tell your doctor immediately if you develop fever, chills, sore throat or mouth ulcers or other signs of frequent infections. In rare cases, Lumin can cause a shortage of white blood cells, resulting in the lowering of the body resistance to infection. These symptoms may appear after 4-6 weeks of treatment.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.

Things you must not do

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

Do not suddenly stop taking Lumin or lower the dose without first checking with your doctor. Do not let yourself run out of tablets over the weekend or on holidays. If you suddenly stop taking Lumin, you may feel unwell, sick in the stomach or have a headache.

Your doctor will tell you how to gradually reduce the amount of Lumin you are taking before stopping completely.

Do not stop taking Lumin even if you feel better unless advised by your doctor.

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

Do not give Lumin to anyone else, even if they have the same condition as you.

Things to be careful of

Do not drink alcohol while taking Lumin. Combining alcohol with Lumin can make you more drowsy, dizzy or lightheaded. Your doctor may suggest you avoid alcohol while being treated with Lumin.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Lumin. Lumin helps most people with depression, but it may have unwanted side effects in some 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 to answer 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 worry you:

  • tiredness, drowsiness or lack of energy
  • dry mouth
  • dizziness on standing up, especially when getting up from a sitting or lying down position
  • dizziness, faintness
  • weakness
  • tremor
  • headache
  • dry mouth
  • constipation
  • weight gain
  • impotence
  • breast enlargement in men
  • restless legs
  • ringing or persistent noise in the ears
  • nasal congestion
  • hepatitis (inflammation of the liver)

Tell your doctor as soon as possible if you notice any of the following:

  • skin rash
  • itching
  • vision problems
  • tingling or numbness of the hands or feet
  • painful, swollen joints
  • aching muscles, muscle tenderness or weakness, not caused by exercise
  • sudden switch of mood to one of excitement, overactivity, talkativeness and uninhibited behaviour
  • confusion, agitation, irritability, hostility (aggressiveness), unusual changes in behaviour.

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

  • you have thoughts of harming or killing yourself
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers
  • bruising or bleeding more easily than normal, nosebleeds
  • tiredness, headaches, being short of breath when exercising
  • fits or convulsions
  • yellowing of the eyes or skin (jaundice)
  • slow heart beat
  • changes to your heart rhythm (fast, irregular heartbeat) and/or fainting which could be symptoms of a life-threatening condition known as Torsades de Pointes
  • chest pain
  • shortness of breath (sometimes with tiredness, weakness and reduced ability to exercise), which may occur together with swelling of the feet or legs due to fluid build up
  • stiffness in the body, involuntary movements, a sudden increase in body temperature, extremely high blood pressure and severe convulsions (Neuroleptic Malignant Syndrome).

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Lumin

Storage

Keep Lumin where children cannot reach it. A locked cupboard a least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in a cool dry place where the temperature stays below 30°C. Protect from light.

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

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

Disposal

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

Medicines should not be disposed of via wastewater or household waste. These measures will help protect the environment.

Product description

What it looks like

Lumin is available in 2 strengths:

  • Lumin 10 - round, white tablet, marked "MI 10" on one side and "G" on the other side
  • Lumin 20 - round, white tablet, marked "MI 20" on one side and "G" on the other side.

Each pack contains 50 tablets.

Ingredients

The active ingredient in Lumin is mianserin (as mianserin hydrochloride):

  • each Lumin 10 tablet contains 10 mg of mianserin hydrochloride
  • each Lumin 20 tablet contains 20 mg of mianserin hydrochloride.

The tablets also contain:

  • pregelatinised maize starch
  • colloidal anhydrous silica
  • microcrystalline cellulose
  • calcium hydrogen phosphate
  • magnesium stearate
  • carnauba wax
  • Opadry White Y-1-7000 (contains colour 171).

Lumin tablets contain trace amounts of sulfites. Lumin tablets are gluten free.

Supplier

Lumin is supplied by:

Alphapharm Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

Lumin 10 - AUST R 55272

Lumin 20 - AUST R 55273

This leaflet was prepared on 20 December 2019.

Lumin_cmi\Dec19/00

Published by MIMS March 2020

BRAND INFORMATION

Brand name

Lumin

Active ingredient

Mianserin hydrochloride

Schedule

S4

 

1 Name of Medicine

Mianserin hydrochloride.

6.7 Physicochemical Properties

Chemical name: 1,2,3,4,10,14b-hexahydro- 2-methyldibenzo[c,f] pyrazino [1,2-a]azepine monohydrochloride.
Molecular formula: C18H20N2HCl. Molecular weight: 300.8.
Mianserin hydrochloride is an odourless, creamy white, crystalline powder that is soluble in water, ethanol, methanol and chloroform.

Chemical structure.


CAS number.

21535-47-7.

2 Qualitative and Quantitative Composition

Mianserin belongs to the tetracyclic series of antidepressant compounds, the piperazinoazepines. These are chemically different from the common tricyclic antidepressants.
Each Lumin 10 tablet contains 10 mg of mianserin hydrochloride and each Lumin 20 tablet contains 20 mg of mianserin hydrochloride as the active ingredient.
Lumin also contains trace amounts of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Lumin 10: 10 mg tablet: white, film coated, normal convex, marked MI 10 on one side, G on reverse.
Lumin 20: 20 mg tablet: white, film coated, normal convex, marked MI 20 on one side, G on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Mianserin belongs to the piperazino-azepine group of compounds which are chemically not related to the tricyclic antidepressants (TCAs). Its structure lacks the basic side chain which is considered to be responsible for the anticholinergic activity of the TCAs. It increases central noradrenergic neurotransmission by α2-autoreceptor blockade and noradrenaline reuptake inhibition. In addition, interactions with serotonin receptors in the central nervous system have been found. Human pharmaco-electroencephalographic (EEG) studies have confirmed the antidepressant profile of mianserin hydrochloride.
The antidepressant efficacy of mianserin hydrochloride has been demonstrated in placebo controlled trials and has been shown to be similar to other currently used antidepressants. Moreover, it possesses anxiolytic and sleep improving properties which are of value in treating patients with anxiety or sleep disturbances associated with depressive illness. The histamine H1- and α1-antagonistic activity of mianserin hydrochloride is thought to be responsible for its sedative properties.
Mianserin hydrochloride is well tolerated, also by the elderly and by patients with cardiovascular disease. At therapeutically effective doses mianserin hydrochloride has virtually no anticholinergic activity and has practically no effect on the cardiovascular system. As compared to the TCAs, it causes less cardiotoxic effects on overdose. It does not antagonise the action of sympathicomimetic agents and antihypertensive drugs which interact with adrenergic receptors (e.g. bethanidine) or α2-receptors (e.g. clonidine, methyldopa).

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

After oral administration, mianserin hydrochloride is rapidly and well absorbed reaching peak plasma levels within 3 hours. The bioavailability is approximately 20%. Binding of mianserin to plasma proteins is approximately 95%. The half-life of elimination (21-61 hours) is sufficient to justify once a day dosing. Steady-state plasma levels are reached within six days. Mianserin is extensively metabolised and eliminated via the urine and faeces within seven to nine days. Major pathways of biotransformation are demethylation and oxidation, followed by conjugation.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of major depression.

4.3 Contraindications

Hypersensitivity to mianserin or any of the excipients (see Section 6.1 List of Excipients.).
Mania.
Severe liver disease.
Concomitant use of mianserin with monoamine oxidase (MAO) inhibitors (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 a history of suicide related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. 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 disorder 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 major depressive disorder or for any other condition (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 Lumin should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Bipolar disorder.

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 bipolar is being treated, it can transform into the manic phase. Patients should be closely monitored and mianserin discontinued in any patient with signs or symptoms of a mixed/ manic episode.

Effects on the blood.

Bone marrow depression, usually presenting as neutropenia, agranulocytosis and thrombocytopenia have been reported during treatment with mianserin hydrochloride. These reactions have occurred most commonly after 4 to 6 weeks of treatment. Patients complaining of sore throat, stomatitis, fever, malaise, flu-like symptoms or other signs of infection should discontinue treatment with mianserin, and a full blood count should be obtained. Elderly patients who have a white blood cell disorder should have a full blood count performed every 4 weeks during the first 3 months of treatment.

Effects on the cardiovascular system.

Although mianserin hydrochloride at therapeutic doses has not been shown to have cardiotoxic effects, caution should be exercised in treating patients with cardiac impairment (e.g. heart block, recent myocardial infarction and unstable heart disease) who should be monitored carefully.
QT prolongation and ventricular arrhythmias (including Torsades de Pointes) have been reported during the postmarketing use of mianserin hydrochloride (see Section 4.8 Adverse Effects (Undesirable Effects)). Mianserin hydrochloride should be used with caution in patients with risk factors for QT prolongation/ TdP including congenital long QT syndrome, age > 65 years, female sex, structural heart disease/ left ventricular (LV) dysfunction, renal or hepatic disease, use of medicines that inhibit the metabolism of mianserin hydrochloride, and the concomitant use of other QTc prolonging medicines (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Hypokalaemia and hypomagnesaemia should be corrected prior to treatment. Consideration should be given to stop mianserin hydrochloride treatment or reducing the dose if the QTc interval is > 500 ms or increases by > 60 ms.

Effects on motor coordination.

Mianserin hydrochloride, especially in the first days of treatment, may impair concentration and psychomotor skills and hence ability to drive or engage in any activity requiring alertness may be impaired. This risk is increased if alcohol is taken concomitantly with mianserin hydrochloride.

Effects on the eye.

Patients with narrow angle glaucoma should be monitored, even though anticholinergic side effects are not expected with Lumin therapy.

Epileptogenic effect.

As clinical experience is lacking in patients suffering from epilepsy, care must be exercised. Mianserin hydrochloride may lower the convulsive threshold in such patients. It may, therefore, be necessary to adjust the dose of anticonvulsants, if administered. Convulsions have also been reported in nonepileptic patients. If convulsions occur, Lumin therapy should be discontinued. However, mianserin products, including Lumin, should be avoided, if possible, in patients with epilepsy.

Effects on the prostate.

Patients with symptoms suggestive of prostatic hypertrophy should be monitored, even though anticholinergic side effects are not expected with Lumin.

Psychiatric effects.

Mianserin hydrochloride, like other antidepressants, may precipitate hypomania in susceptible subjects with bipolar depressive illness. In such a case treatment with mianserin should be withdrawn. The possibility of the depressed patient attempting suicide should be borne in mind, and large amounts of the drug should not be held by the patient.

Effects on metabolism.

Slight alterations of the glucose tolerance curve and insulin levels have been observed in some patients with diabetes mellitus, who were treated with mianserin hydrochloride. Therefore, in such patients, regular monitoring of blood glucose levels is advisable.

Effects on surgery.

Clinicians should inform anaesthetists if surgery becomes necessary during mianserin hydrochloride treatment.

Use in hepatic and renal impairment.

Depressed patients suffering from liver or renal insufficiency should be carefully monitored because of the possibility of increases in serum derived liver enzyme levels (mainly ALT) and impaired metabolism or excretion. If jaundice occurs, Lumin should be discontinued.

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of Lumin for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Lumin should not be used in this age group for the treatment of depression or other psychiatric disorders. (Also see Section 4.4 Special Warnings and Precautions for Use, Clinical worsening and suicide risk.)

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant use of barbiturates with mianserin hydrochloride is not recommended as there may be additive central depressant effects.
Mianserin hydrochloride should not be administered concomitantly with monoamine oxidase inhibitors (such as moclobemide, tranylcypromine and linezolid) or within two weeks after MAOIs have been discontinued. In the opposite way about two weeks should pass before patients treated with mianserin should be treated with MAO inhibitors.
Mianserin hydrochloride may affect the metabolism of coumarin derivatives such as warfarin. Patients receiving warfarin therapy should receive coagulation monitoring when Lumin is initiated or stopped.
It has been shown that alcohol potentiates the impairment of psychomotor skills especially in the initial period of treatment. Patients should be advised to avoid taking alcohol during treatment.
Although there is evidence that the tyramine uptake into peripheral noradrenergic neurones in depressed patients receiving mianserin hydrochloride is not inhibited, it is nevertheless advisable to check the blood pressure regularly in those patients who are concomitantly treated with antihypertensives.
Mianserin hydrochloride has been used with benzodiazepines without apparent ill effect.
Concomitant treatment with antiepileptic drugs that are CYP3A4 inducers (like phenytoin and carbamazepine) can result in reduced plasma levels of mianserin. Dose adjustment should be considered when concomitant treatment with these drugs is initiated or discontinued.
Phenytoin levels need to be monitored.
The risk of QTc prolongation and/or ventricular arrhythmias (e.g. Torsades de Pointes) is increased with concomitant use of other medicines which prolong the QTc interval (e.g. some antipsychotics and antibiotics). Please check the product information of other medicines administered for information on their effects on the QTc interval.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
There is limited experience of the effects of mianserin hydrochloride in human pregnancy and therefore it should not be given to pregnant women or those likely to become pregnant unless the expected benefit outweighs the potential risk.
Available data on the few studies conducted in animals show no evidence of an increase of occurrence of foetal damage, however, the number of implantation sites were significantly reduced in a rat fertility study in which dams were dosed at greater than 3 mg/kg/day. There is only limited evidence of safety in pregnancy.
It is not known whether mianserin hydrochloride is excreted in human milk nor whether it has a harmful effect on newborns. Therefore, it is recommended that mianserin not be given to nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

Reporting frequencies are described as follows, according to CIOMS Working Group III. Very common: > 10%; common: 1 to 10%; uncommon: 0.1 to 1%; rare: 0.01 to 0.1%; very rare: < 0.01%; frequency not known.

Blood and the lymphatic system disorders.

Very rare: blood dyscrasias.

Investigations.

Uncommon: weight gain.

General disorders.

Rare: oedema.

Musculoskeletal and connective tissue disorders.

Rare: arthralgia/ arthritis.

Skin and subcutaneous tissue disorders.

Rare: exanthema.

Nervous system disorders.

Common: sedation (primarily at initiation of treatment). Very rare: convulsions, hyperkinesia (restless legs), neuroleptic malignant syndrome.

Psychiatric disorders.

Rare: hypomania.

Vascular disorders.

Rare: hypotension (postural).

Cardiac disorders.

Very rare: bradycardia. Frequency not known: electrocardiogram, QT prolonged, torsades de pointes.

Hepatobiliary disorders.

Rare: disturbances of liver function including jaundice, hepatitis. Frequency not known: elevated liver enzymes, hepatic function abnormal.

Serious or life threatening reactions.

Blood and the lymphatic system disorders.

Very rare: bone marrow depression resulting in neutropenia, granulocytopenia, leukopenia, agranulocytosis, pancytopenia, thrombocytopenia, anaemia (aplastic, B12 deficiency, haemolytic, hypoplastic, normocytic, sideroblastic).

Cardiac disorders.

Very rare: cardiac arrest, cardiac failure.
These reactions necessitate immediate withdrawal of Lumin therapy and are reversible on stopping treatment.
If jaundice, hypomania or convulsions occur at therapeutic dosages, then treatment should be withdrawn.

Other reactions.

The following adverse events have been reported in association with mianserin hydrochloride use. A causal relationship has not been established.

Gastrointestinal disorders.

Very common: dry mouth, constipation.

Nervous system disorders.

Common: tremor, headache. Rare/ very rare: paraesthesia.

Respiratory, thoracic and mediastinal disorders.

Rare/ very rare: nasal congestion.

Eye disorders.

Rare/ very rare: vision abnormality, diplopia.

Reproductive system and breast disorders.

Rare/ very rare: gynaecomastia, impotence.

Musculoskeletal and connective tissue disorders.

Rare/ very rare: myalgia.

Skin and subcutaneous tissue disorders.

Rare/ very rare: pruritus.

Vascular disorders.

Rare/ very rare: hypertension.

Cardiac disorders.

Rare/ very rare: tachycardia.

Ear and labyrinth disorders.

Rare/ very rare: tinnitus.

Psychiatric disorders.

Rare/ very rare: confusion, agitation.
Cases of suicidal ideation and suicidal behaviours have been reported during mianserin therapy or early after treatment discontinuation (see Section 4.4 Special Warnings and Precautions for Use).

More common reactions.

See Table 1.

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

Lumin tablets should be taken orally between meals, preferably with a little fluid, and swallowed without chewing.

Use in children and adolescents (< 18 years of age).

Lumin should not be used in children and adolescents under the age of 18 years (see Section 4.4 Special Warnings and Precautions for Use).

Adults.

The initial dosage of Lumin should be judged individually. It is recommended that treatment begin with a daily dose of 30 mg given in three divided doses or as a single bedtime dose and be adjusted weekly in the light of the clinical response. The effective daily dose for adult patients usually lies between 30 mg and 90 mg (average 60 mg) in divided doses or as a single bedtime dose. A maximum daily dose of 120 mg should not be exceeded. It is often advantageous to maintain antidepressant treatment for several months after initial clinical improvement has occurred.

Elderly.

Initially, not more than 30 mg daily and increased slowly under close supervision. A reduced dose may also be required for maintenance, as hepatic, renal or cardiovascular function may be impaired.
Pharmacokinetic studies of mianserin in the elderly patient suggest a longer half-life and slower metabolic clearance. This implies that a single night time dose of mianserin hydrochloride should be preferred to divided doses in the elderly patient.

4.7 Effects on Ability to Drive and Use Machines

Mianserin hydrochloride may impair psychomotor performance for the first few days of treatment. In general, depressed patients treated with antidepressants should avoid the performance of potentially dangerous tasks such as driving a motor vehicle or operating machinery.

4.9 Overdose

The toxic effects of mianserin hydrochloride are different from those of the tricyclics and there is no specific antidote.

Symptoms.

Symptoms of acute overdose are generally confined to prolonged sedation. Cardiac arrhythmias, convulsions, severe hypotension and respiratory depression occur rarely. Electrocardiogram QTc prolonged and torsades de pointes has also been reported. ECG monitoring should be undertaken. There is no specific antidote.

Treatment.

Treatment is by gastric lavage with 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)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Pregelatinised maize starch, colloidal anhydrous silica, microcrystalline cellulose, calcium hydrogen phosphate, magnesium stearate, Opadry White Y-1-7000 and carnauba wax.

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

Container type: available in PVC/PVDC/Al blister packs.
Pack sizes: 50 tablets.

6.6 Special Precautions for Disposal

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

Summary Table of Changes