Mirtagen

Patient Information Leaflet

Warning! Keep this leaflet. Information on the immediate packaging is in a foreign language.
Mirtagen (Mirtazapine SmeltTab Mylan 45 mg)
45 mg, orodispersible tablets
Mirtazapinum
Mirtagen and Mirtazapine SmeltTab Mylan 45 mg are different trade names for the same medicine.
Please read all of this 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet:

1. What Mirtagen is and what it is used for
2. What you need to know 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 to treat 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 medicines from the group of monoamine oxidase inhibitors (MAOIs) have been used currently or recently (within the last 2 weeks).

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

If severe skin rash, skin peeling, skin blisters and/or oral mucosal erosions have ever occurred in the patient after using 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 regarding severe skin reactions occur, treatment must be discontinued immediately and medical advice must be sought without delay. If the patient has ever experienced severe skin reactions, re-initiation of treatment with Mirtagen is not recommended.

Children and adolescents

Mirtagen should 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 patient's best interest. If Mirtagen has been prescribed to a patient under 18 years of age and the patient wishes to discuss this, medical advice should be sought 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, puberty, cognitive development 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 suicide. These thoughts may increase when antidepressant treatment is first initiated, as such medicines act slowly, usually taking about 2 weeks or longer to show effect.

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, contact a doctor immediately or go to hospital without delay.

Talking to someone close, such as a 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 your doctor or pharmacist if any of the following conditions are present or have ever occurred:

• seizures (epilepsy)
• liver disorders, including jaundice
• kidney disorders
• heart disorders or family history of heart disorders, including certain types of heart rhythm disorders, recent myocardial infarction, heart failure, or use of specific medicines that may cause heart rhythm disturbances
• low blood pressure
• schizophrenia
• bipolar affective disorders (alternating periods of elevated mood and excitement with depression)
• diabetes (a change in insulin or other antidiabetic medicine dosage may be necessary)
• 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 the adverse effects of antidepressant medicines.

During treatment

Inform your doctor:

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

Mirtagen and other medicines

Do not use Mirtagen together with:

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

Tell your doctor or pharmacist about all medicines currently or recently taken, including those obtained 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 herbal preparations containing St. John's wort Hypericum perforatum (herbal remedies used to treat depression). In very rare cases, serotonin syndrome may occur in patients taking Mirtagen alone or in combination with these medicines. Some symptoms include fever, sweating, increased heart rate, diarrhoea, involuntary muscle contractions, shivering, increased reflexes, restlessness, mood changes and loss of consciousness. Seek immediate medical advice 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). When used in combination with Mirtagen, these medicines may increase mirtazapine blood levels. Inform your doctor if you are taking these medicines. A reduction in the dose of Mirtagen may be necessary, and after stopping treatment with these medicines, the dose of Mirtagen may need to be increased.

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 your doctor if you are taking these medicines. An increase in the dose of Mirtagen may be necessary, and after stopping treatment with these medicines, the dose of Mirtagen may need to be reduced.
• warfarin, a medicine used to prevent blood clots. Mirtagen may enhance the effect of warfarin. Inform your doctor if you are taking these medicines. When used in combination with Mirtagen, monitoring of blood parameters is recommended.

Mirtagen and alcohol

Drinking alcohol while taking this medicine may cause drowsiness. 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 your doctor whether to continue treatment. If Mirtagen is taken during pregnancy or shortly before delivery, newborns should be monitored for possible adverse effects.

Ensure that your midwife and/or doctor are aware that you are 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 your midwife or doctor immediately.

Ask your doctor whether you can breastfeed while taking Mirtagen.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your 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 your concentration and alertness are not impaired.

Mirtagen contains aspartame (E 951)

This medicine contains 9 mg of aspartame in each orally disintegrating tablet. Aspartame 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 use Mirtagen

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you have any doubts,
you should consult your 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, your doctor may
recommend increasing the dose to the most appropriate level for the patient (from 15 to 45 mg daily).
The usual dose is generally recommended for patients of various ages. However, in elderly patients or those with
kidney or liver disease, your 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 at bedtime. However, your doctor may recommend taking the medicine in two divided doses – one in the morning and one at bedtime. The higher dose should be taken at bedtime.
Instructions for taking orally disintegrating tablets:
The tablets are for oral use.
1. Do not crush the orally disintegrating tablet
To avoid crushing the orally disintegrating tablet, do not press on the blister pack containing the tablet (Figure A).

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

Figure 1.
3. Peel off the foil
Carefully peel off the foil cover, 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 to work after 1 to 2 weeks, and your well-being will begin to improve after 2 to 4 weeks.
It is important to discuss the effects of Mirtagen with your doctor during the first weeks of treatment.
After 2 to 4 weeks from starting Mirtagen, you should discuss your treatment progress with your doctor.
If there is no adequate clinical response, your doctor may increase the dose. After another 2–4 weeks, you should again review your treatment progress with your 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 Mirtagen than recommended
If you or anyone else takes more Mirtagen than prescribed, contact your doctor immediately.
The most common signs of Mirtagen overdose (without other medicines or alcohol) include drowsiness,
disorientation, changes in heart rhythm (fast heartbeat, irregular heartbeat) and/or fainting.
These may be symptoms of life-threatening ventricular arrhythmias known as "torsade de pointes".
If you forget to take Mirtagen
If you forget to take a dose of Mirtagen that is to be taken once daily:
Do not take the missed dose; simply skip it.
Take the next dose the following day at the usual time.
Do not take a double dose to make up for the missed tablet.
If you forget to take a dose of Mirtagen that 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. Continue treatment the next day with the usual morning and evening doses.
Stopping Mirtagen
You should stop taking Mirtagen only after consulting your doctor.
Do not stop taking the medicine too early, as this may cause the illness to return. If improvement occurs, discuss this with your doctor. Your doctor will advise when it is safe to stop treatment.
Suddenly stopping Mirtagen may cause nausea, dizziness, agitation or anxiety, and headache. These symptoms can be avoided by gradually discontinuing the medicine.
Your doctor will advise you on how to gradually reduce the dose of Mirtagen.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
If any of the following symptoms occur, stop taking the medicine
Mirtagen and immediately contact a 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 mild to severe abdominal pain radiating to the back.

Frequency unknown (frequency cannot be estimated from available data):

• seizures (fits);
• yellowing of the skin or eyes, which may indicate liver problems (jaundice);
• a combination of symptoms such as fever of unknown cause, sweating, increased heart rate, diarrhoea, involuntary muscle contractions, chills, increased reflexes, restlessness, 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 in the form of target-like spots or round patches, often with blisters in the center; skin peeling; ulceration of the mucous membranes 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 hypersensitivity syndrome);
• 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);
• breakdown of muscle tissue causing muscle pain, tenderness, stiffness, and (or) weakness, and dark discoloration of urine (rhabdomyolysis);
• difficulty in passing urine or emptying the bladder;
• lower than normal level of sodium in the blood, 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 effects:
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;
• tremors or shaking;
• 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 the 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, e.g. burning, stinging, or tingling (paresthesia);
• restless legs syndrome;
• fainting;
• abnormal sensations in the mouth (oral hypoaesthesia);
• 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 (muscle clonic seizures);
• aggressive behaviour;
• increased activity of liver enzymes seen in blood tests.

Frequency unknown (frequency cannot be estimated from available data):

• abnormal sensations in the mouth, e.g. burning, stinging, or tingling (oral paresthesia);
• swelling of the mouth;
• low level of sodium in the blood (hyponatremia) seen in blood tests;
• increased salivation;
• sleepwalking;
• difficulty speaking;
• increased level of prolactin hormone in the blood (hyperprolactinaemia, including symptoms such as breast enlargement and (or) milky discharge from the nipple).

Additional adverse effects in children and adolescents
The following adverse effects were frequently observed in clinical trials involving children under 18 years of age: urticaria and increased blood triglyceride levels.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects 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 effects 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 stated month.
No special storage conditions required.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Mirtagen contains

• The active substance is mirtazapine. Each orodispersible tablet contains 45 mg of mirtazapine.
• Other ingredients are: crospovidone, mannitol (E 421), microcrystalline cellulose, aspartame (E 951) (see section 2 “Mirtagen contains aspartame (E 951) and mannitol (E 421)”), strawberry-guarana flavour, peppermint flavour, colloidal anhydrous silica, and magnesium stearate.

What Mirtagen looks like and contents of the pack
Round, white tablets, marked with the letter ‘A’ on one side and ‘38’ on the other.
Pack size: 30 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:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Marketing authorisation number in the Netherlands, country of export: RVG 34054
Parallel import authorisation number: 306/22