Mirtazepine

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Mirtagen (Mirtazapine SmeltTab Mylan 15 mg)
15 mg, orodispersible tablets
Mirtazapinum
Mirtagen and Mirtazapine SmeltTab Mylan 15 mg are different brand names of the same medicine.
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse effects, including any adverse effects not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What Mirtagen is and what it is used for
2. Important information before taking Mirtagen
3. How to take Mirtagen
4. Possible side effects
5. How to store Mirtagen
6. Contents of the pack and other information

1. What Mirtagen is and what it is used for

Mirtagen belongs to a group of medicines called antidepressants.
Mirtagen is used in the treatment of depression in adults.

2. Important information before using Mirtagen

When not to use Mirtagen:

• if the patient is allergic to mirtazapine or any of the other ingredients of this medicine (listed in section 6),
• if the patient is currently or has recently (within the last 2 weeks) been taking medicines from the group of monoamine oxidase inhibitors (MAOIs).

Warnings and precautions
When not to use Mirtagen or consult a doctor before starting treatment:

If the patient has ever experienced severe skin rash, skin peeling, skin blisters and/or oral mucosal erosions after taking Mirtagen or other medicines. Severe skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during treatment with Mirtagen. If any of the symptoms described in section 4 relating to severe skin reactions occur, treatment must be discontinued immediately and the patient must seek medical advice without delay. Mirtagen should not be restarted if the patient has previously experienced severe skin reactions.

Children and adolescents
Mirtagen must not be used in children and adolescents under 18 years of age, as its efficacy has not been established. It should also be emphasized that patients under 18 years of age taking medicines of this class are at increased risk of adverse effects such as suicidal behaviour, suicidal thoughts and hostility (particularly aggression, defiant behaviour and anger). Nevertheless, a doctor may prescribe Mirtagen to patients under 18 years of age if he or she considers it to be in the best interest of the patient. If a doctor has prescribed Mirtagen to a patient under 18 years of age and the patient wishes to discuss this, the patient should consult the doctor again. If the above-mentioned symptoms develop or worsen in patients under 18 years of age taking Mirtagen, this should be reported to the doctor. Furthermore, the long-term impact of Mirtagen on safety with regard to growth, maturation and cognitive and behavioural development in this age group has not yet been established. Significant weight gain has been observed more frequently in patients treated with mirtazapine in this age group compared to adults.

Suicidal thoughts and worsening of depression and anxiety disorders
Patients with depression may sometimes have thoughts of self-harm or suicidal ideation. These thoughts may increase when antidepressant treatment is first initiated, as such medicines act slowly, usually taking about 2 weeks or sometimes longer.
This may occur:

• if the patient has previously experienced thoughts of self-harm or suicide,
• if the patient is a young adult. Clinical trial data have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders treated with antidepressants. If thoughts of self-harm or suicidal thoughts occur, the patient should contact a doctor immediately or go to hospital without delay.

Talking to a close family member or friend may be helpful. The patient may inform these individuals about their depression and ask them to read this leaflet so they can alert the patient if they notice worsening of their condition or unusual changes in behaviour.

Before starting treatment with Mirtagen, discuss with the doctor or pharmacist if the patient has or has ever had any of the following conditions:

• seizures (epilepsy)
• liver disorders, including jaundice
• kidney disorders
• heart disorders or family history of heart disorders, including certain types of heart rhythm disturbances, recent myocardial infarction, heart failure, or use of certain medicines that may cause heart rhythm disturbances
• low blood pressure
• schizophrenia
• bipolar affective disorders (alternating periods of elevated mood and excitement with depression)
• diabetes (may require adjustment of insulin or other antidiabetic medicines)
• eye disorders, such as increased intraocular pressure (glaucoma)
• difficulty in passing urine, which may be due to prostate enlargement.

Elderly patients
Elderly patients are often more sensitive, particularly to adverse effects of antidepressant medicines.

During treatment
Inform the doctor:

• if symptoms of infection occur, such as high fever, sore throat or mouth ulcers. In rare cases, these symptoms may indicate bone marrow dysfunction affecting blood cell production. Although rare, these symptoms most commonly occur 4–6 weeks after starting treatment.

Mirtagen and other medicines
Do not take Mirtagen together with:

• monoamine oxidase inhibitors (MAOIs) or within two weeks of stopping such treatment. Do not start taking Mirtagen within two weeks of stopping MAOIs. Examples of MAOIs include moclobemide, tranylcypromine (antidepressants) and selegiline (used in the treatment of Parkinson's disease).

Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including medicines available without a prescription, and particularly:

• other antidepressants such as SSRIs (e.g. citalopram), venlafaxine, L-tryptophan or triptans (used to treat migraine), tramadol (a painkiller), linezolid (an antibiotic), lithium salts (used in the treatment of certain psychiatric disorders), and preparations containing St. John's wort Hypericum perforatum (herbal remedies used for depression). In very rare cases, serotonin syndrome may occur in patients taking Mirtagen alone or in combination with these medicines. Some of its symptoms include fever, sweating, increased heart rate, diarrhoea, involuntary muscle contractions, chills, increased reflexes, restlessness, mood changes and loss of consciousness. Contact a doctor immediately if several of these symptoms occur together.
• medicines used to treat anxiety and insomnia, such as benzodiazepines, e.g. diazepam, chlordiazepoxide.
• medicines used to treat schizophrenia, such as olanzapine.
• medicines used to treat allergies, such as cetirizine.
• medicines used to treat severe pain, such as morphine. Mirtagen in combination with these medicines may increase the drowsiness caused by them.

Medicines that increase mirtazapine levels in the blood:

• medicines used to treat infections; antibacterial agents (such as erythromycin), antifungal agents (such as ketoconazole), medicines used to treat HIV and AIDS (such as HIV protease inhibitors, e.g. ritonavir, nelfinavir); antidepressants (such as nefazodone) and medicines used to treat stomach ulcers (such as cimetidine). In combination with Mirtagen, these medicines may increase mirtazapine blood levels. Inform the doctor if taking these medicines. It may be necessary to reduce the dose of Mirtagen, and after stopping these medicines, to increase the dose of Mirtagen.

Medicines that decrease mirtazapine levels in the blood:

• carbamazepine and phenytoin, medicines used to treat epilepsy; rifampicin, a medicine used to treat tuberculosis. In combination with Mirtagen, these medicines may reduce Mirtagen blood levels. Inform the doctor if taking these medicines. It may be necessary to increase the dose of Mirtagen, and after stopping these medicines, to reduce the dose of Mirtagen.
• warfarin, a medicine used to prevent blood clots. Mirtagen may enhance the effect of warfarin. Inform the doctor if taking these medicines. When Mirtagen is used concomitantly with warfarin, monitoring of blood parameters is recommended.

Mirtagen and alcohol
Drowsiness may occur if alcohol is consumed while taking this medicine.
It is best to avoid alcohol while taking Mirtagen.

Pregnancy and breastfeeding
Limited experience with the use of Mirtagen in pregnant women does not indicate an increased risk. However, caution should be exercised during pregnancy.
If pregnancy occurs or is planned while taking Mirtagen, consult the doctor whether the treatment should be continued. If Mirtagen is taken during pregnancy or shortly before delivery, the newborn should be monitored for possible adverse effects.
Ensure that the midwife and/or doctor are aware that the patient is taking Mirtagen.
Use of similar medicines (SSRIs) during pregnancy may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), causing rapid breathing and cyanosis (bluish skin). Symptoms usually begin within 24 hours after birth. If these symptoms occur in the newborn, contact the midwife or doctor immediately.
Ask the doctor whether breastfeeding is permitted while taking Mirtagen.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.

Driving and operating machinery
Mirtagen may reduce alertness and the ability to concentrate. Before driving or operating machinery, ensure that concentration and alertness are not impaired.

Mirtagen contains aspartame (E 951)
This medicine contains 3 mg of aspartame (E 951) in each orally disintegrating tablet.
Aspartame (E 951) is a source of phenylalanine. It may be harmful to patients with phenylketonuria.
This is a rare genetic disorder in which phenylalanine accumulates in the body due to impaired excretion.

3. How to take Mirtagen

This medicine should always be taken as directed by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
Mirtagen is available in the following strengths: 15 mg, 30 mg, 45 mg.
Dosage
The recommended starting dose is 15 or 30 mg once daily. After several days of treatment, the doctor may
recommend increasing the dose to the most appropriate level for the patient (from 0.15 to 45 mg once daily).
The usual dose is recommended for patients of various ages. However, in elderly patients or in those with
kidney or liver disease, the doctor may recommend a different dose.
When to take Mirtagen
Mirtagen should be taken every day at the same time.
Mirtagen is best taken as a single dose before going to bed. However, the doctor may recommend taking the
medicine in two divided doses – one in the morning and one in the evening before going to bed. The higher
dose should be taken before going to bed.
Instructions for taking orally disintegrating tablets:
The tablets should be taken by mouth.
1. Do not crush the orally disintegrating tablet
To avoid crushing the orally disintegrating tablet, do not press on the pouch containing the tablet (Figure A).

Figure A.
2. Detach the pouch with the tablet
Each blister pack contains 6 pouches with tablets, separated by perforated lines. Bend the blister pack and
detach one pouch along the perforated line (Figure 1).

Figure 1.
3. Peel off the foil
Carefully peel off the foil starting from the corner (Figure 2).

Figure 2.
4. Remove the orally disintegrating tablet
Remove the orally disintegrating tablet with a dry hand and place it on the tongue.
(Figure 3).

Figure 3.
The tablet dissolves quickly and can be swallowed without water.
When to expect improvement in well-being
Mirtagen usually starts working after 1 to 2 weeks, and well-being begins to improve after 2 to 4 weeks.
It is important to discuss the effects of Mirtagen with the doctor during the first weeks of treatment.
After 2 to 4 weeks of taking Mirtagen, the progress of treatment should be reviewed with the doctor.
If there is no adequate clinical response, the doctor may increase the dose. After another 2–4 weeks, the
treatment progress should be reviewed again with the doctor. Treatment should be continued until symptoms
have completely resolved, which usually takes 4 to 6 months.
Use in children and adolescents under 18 years of age
Mirtagen should not be used in children and adolescents under 18 years of age (see section 2 “Children and
adolescents”).
Taking more than the recommended dose of Mirtagen
If the patient or anyone else takes more Mirtagen than recommended, contact the doctor immediately.
The most common signs of Mirtagen overdose (without other medicines or alcohol) are drowsiness,
disorientation, changes in heart rhythm (rapid heartbeat, irregular heartbeat) and/or fainting. These may be
symptoms of life-threatening ventricular arrhythmias known as "torsade de pointes".
If you miss a dose of Mirtagen
If you forget to take your medicine which is to be taken once daily
Do not take the missed dose of Mirtagen; simply skip it.
Take the next dose the next day at the usual time.
Do not take a double dose to make up for the missed tablet.
If you forget to take your medicine which is to be taken twice daily
If you forget the morning dose, take it together with the evening dose.
If you forget the evening dose, do not take it together with the morning dose; skip it and continue treatment
with the usual morning and evening doses.
If you forget both doses, do not try to make them up; skip them. The next day, continue treatment with the
usual morning and evening doses.
Stopping Mirtagen
Mirtagen should only be discontinued after consulting with the doctor.
Do not stop taking the medicine too early, as this may cause the illness to return. If improvement occurs,
discuss it with the doctor. The doctor will advise when treatment can be stopped. Stopping Mirtagen suddenly
may cause nausea, dizziness, agitation or anxiety, headache. These symptoms can be avoided by gradually
stopping the medicine.
The doctor will advise how to gradually reduce the doses of the medicine.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the symptoms listed below occur, stop taking the medicine
Mirtagen and immediately contact your doctor or go to the emergency department of the nearest hospital:
Rare (may affect up to 1 in 1,000 patients):

• inflammation of the pancreas causing moderate to severe stomach pain radiating to the back.

Frequency not known (frequency cannot be estimated from the available data):

• seizures (convulsions)
• yellowing of the skin or eyes, which may indicate liver dysfunction (jaundice)
• a combination of symptoms such as fever of unknown origin, sweating, increased heart rate, diarrhoea, (involuntary) muscle contractions, chills, overactive reflexes,
  anxiety, mood changes, loss of consciousness. In very rare cases, these may be
  signs of serotonin syndrome
• thoughts of self-harm or suicide or suicide attempts
• red skin lesions on the trunk appearing as target-shaped or circular spots, often with blisters in the central area; skin peeling; mucosal ulceration of the mouth, throat, nose, eyes, and genital organs. Such severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• widespread rash, high fever, and swollen lymph nodes (DRESS syndrome, i.e. drug reaction with eosinophilia and systemic symptoms)
• signs of infection such as sudden high fever, sore throat, mouth ulcers (agranulocytosis). Mirtazapine may cause disturbances in blood cell production (bone marrow suppression). Some people become less resistant to infections because mirtazapine may cause a temporary deficiency of white blood cells (granulocytopenia). In rare cases, mirtazapine may also cause deficiency of red and white blood cells as well as platelets (aplastic anaemia), deficiency of platelets (thrombocytopenia), or increased number of white blood cells (eosinophilia)
• muscle tissue breakdown causing muscle pain, tenderness, stiffness, and (or) weakness and dark-coloured urine (rhabdomyolysis)
• difficulty in passing urine or emptying the bladder
• lower than normal blood sodium levels, which may cause weakness and may be mistaken for muscle pain. This may result from inappropriate secretion of antidiuretic hormone, leading to water retention in the body and dilution of the blood, thereby reducing sodium levels.

Other adverse reactions:
Very common (may affect more than 1 in 10 patients):

• increased appetite or weight gain
• drowsiness
• headache
• dry mouth.

Common (may affect up to 1 in 10 patients):

• lethargy
• dizziness
• convulsions or tremor
• nausea
• diarrhoea
• vomiting
• constipation
• rash or skin eruptions
• joint pain, muscle pain
• back pain
• dizziness or fainting upon sudden change in body position, e.g. when standing up (orthostatic hypotension)
• swelling (usually of ankles or feet) due to fluid accumulation (oedema)
• fatigue
• vivid dreams
• confusion
• feeling of anxiety
• sleep problems.

Uncommon (may affect up to 1 in 100 patients):

• feeling of excitement or agitation (mania)
• unusual skin sensations, such as burning, tingling, or pins and needles (paraesthesia)
• restless legs syndrome
• fainting
• abnormal sensations in the mouth (oral paraesthesia)
• low blood pressure
• nightmares
• agitation
• seeing, feeling, or hearing things that are not real (hallucinations)
• urgent need for movement.

Rare (may affect up to 1 in 1,000 patients):

• muscle twitching or contractions (clonic muscle convulsions)
• aggressive behaviour
• increased liver enzyme activity visible in blood tests.

Frequency not known (frequency cannot be estimated from the available data):

• abnormal sensations in the mouth, such as burning, tingling, or pins and needles (oral paraesthesia)
• swelling of the mouth
• low blood sodium levels (hyponatraemia) visible in blood tests
• increased salivation
• sleepwalking
• difficulty speaking
• increased levels of prolactin hormone in blood (hyperprolactinaemia, including symptoms such as breast enlargement and (or) milky nipple discharge).

Additional adverse reactions in children and adolescents
The following adverse reactions were frequently observed in clinical trials involving children under 18 years of age: urticaria and increased blood triglyceride levels.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Mirtagen

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
No special storage conditions are required for this medicinal product.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the packaging and other information

What the medicine Mirtagen contains

• The active substance is mirtazapine. Each orodispersible tablet contains 15 mg of mirtazapine.
• The other ingredients are: crospovidone, mannitol (E 421), microcrystalline cellulose, aspartame (E 951) (see section 2 "Mirtagen contains aspartame (E 951)"), strawberry-guarana flavour, peppermint flavour, colloidal anhydrous silica, and magnesium stearate.

What Mirtagen looks like and contents of the pack
Mirtagen is an orodispersible tablet.
The orodispersible tablets are round, white, marked on one side with the letter "A" and "36" on the other side.
Mirtagen is available in packs containing 30 or 96 orodispersible tablets.
For more detailed information, please contact the Marketing Authorisation Holder or the parallel importer.
Marketing Authorisation Holder in the Netherlands, country of export:
Mylan Pharmaceuticals Ltd
Damastown Industrial Park
Mulhuddart
Dublin 15
Dublin
Ireland
Manufacturer:
Gerard Laboratories
35/36 Baldoyle Industrial Estate
Grange Road
Dublin 13
Ireland
Mylan Hungary Kft.
Mylan utca 1
H-2900 Komarom
Hungary
Parallel importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Marketing Authorisation number in the Netherlands, country of export: RVG 34052
Parallel import licence number: 123/24