Remeron

PACKAGE INSERT

Package insert: information for the patient

Remeron 15 mg orodispersible tablets, 30 mg orodispersible tablets

mirtazapine
Please read this entire leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Remeron is and what it is used for

Remeron belongs to a group of medicines called antidepressants.
Remeron is used to treat depressive disorders in adults.
It will take 1 to 2 weeks before Remeron starts to work. You may start to feel better after a period of
2 to 4 weeks. You should contact your doctor if you do not feel better or if you feel worse after
2 to 4 weeks. Further information is provided in section 3 under the heading “When to expect to feel better”.

2. What you should know before taking Remeron

Do not take Remeron

• if you are allergic to mirtazapine or to any of the other ingredients of this medicine (listed in section 6). In this case, you must speak to your doctor as soon as possible before taking Remeron.
• if you are taking or have recently taken (within the last 2 weeks) medicines called monoamine oxidase inhibitors (MAO-I).

Warnings and precautions
Talk to your doctor or pharmacist before taking Remeron.
Tell your doctor before taking Remeron
If you have previously experienced a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking Remeron.
Children and adolescents
Remeron is generally not recommended for use in children and adolescents under 18 years of age, as efficacy has not been demonstrated. Furthermore, it should be noted that in patients under 18 years of age, this class of medicines is associated with a higher risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (particularly aggression, hostile behavior, and anger). Nevertheless, a doctor may decide to prescribe Remeron to patients under 18 years of age if they consider it to be in their best interest. If your doctor has prescribed Remeron to a patient under 18 years of age and you would like further clarification, please consult your doctor directly. Inform your doctor if any of the symptoms described above appear or worsen in patients under 18 years of age receiving Remeron. In addition, the long-term safety effects of Remeron in this age group with regard to growth, maturation, and cognitive and behavioral development have not yet been established. Moreover, in this age group, a more pronounced weight gain has been observed during treatment with Remeron compared to adults.
Suicidal thoughts and worsening depression
If you are depressed, you may sometimes think about harming yourself or ending your life. These thoughts may increase shortly after starting antidepressant treatment, as these medicines require time to take effect, usually about two weeks but sometimes longer.
You are more likely to have such thoughts if:

• you have previously thought about ending your life or harming yourself.
• you are a young adult. Clinical studies have shown an increased risk of suicidal behavior in adults under 25 years of age with psychiatric disorders treated with antidepressants. → If at any time you find yourself thinking about harming yourself or ending your life, contact your doctor or go to hospital immediately.

It may be helpful to confide in a family member or friend who is aware of your depression and ask them to read this leaflet. You may ask them to inform you if they believe your depression is worsening or if they are concerned about changes in your behavior.
Pay special attention when taking Remeron also

• if you currently suffer or have previously suffered from any of the following conditions. → If you have not already done so, inform your doctor about these conditions before taking Remeron.
• seizures (epilepsy). If you begin to have seizures or if seizures become more frequent, stop taking Remeron and contact your doctor immediately;
• liver disease, including jaundice. If you develop jaundice, stop taking Remeron and contact your doctor immediately;
• kidney disease;
• heart disease or low blood pressure;
• schizophrenia. If psychotic symptoms, such as paranoid thoughts, become more frequent or severe, contact your doctor immediately;
• manic depression (alternating periods of euphoria/hyperactivity and depressed mood). If you start feeling euphoric or overexcited, stop taking Remeron and contact your doctor immediately;
• diabetes (adjustment of insulin or other antidiabetic medication doses may be necessary);
• eye disorders, such as increased eye pressure (glaucoma);
• difficulty urinating, which may be caused by an enlarged prostate;
• certain types of heart conditions that may affect heart rhythm, recent heart attack, heart failure, or if you are taking certain medicines that may affect heart rhythm.
• If you develop signs of infection, such as unexplained high fever, sore throat, and mouth ulcers. → Stop taking Remeron and contact your doctor immediately for a blood test. In rare cases, these symptoms may indicate a disorder in blood cell production in the bone marrow. Although rare, these symptoms most commonly occur after 4–6 weeks of treatment.
• if you are elderly. You may be more sensitive to the adverse effects of antidepressants.
• Serious skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of Remeron. Discontinue use and contact your doctor immediately if you notice any of the symptoms described in section 4 related to these serious skin reactions. Remeron treatment should not be restarted if you have previously experienced severe skin reactions.

Other medicines and Remeron
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not take Remeron in combination with:

• monoamine oxidase inhibitors (MAO inhibitors). In addition, do not take Remeron within two weeks after stopping MAO inhibitors. Likewise, if you stop taking Remeron, do not take MAO inhibitors within two weeks after stopping Remeron. Examples of MAO inhibitors include moclobemide, tranylcypromine (both are antidepressants), and selegiline (used in Parkinson’s disease).

Be cautious when taking Remeron in combination with:

• antidepressants such as SSRIs, venlafaxine, and L-tryptophan or triptans (used to treat migraine), tramadol (for pain treatment), linezolid (an antibiotic), lithium (used to treat certain psychiatric conditions), methylene blue (used to treat high levels of methemoglobin in the blood), and St. John’s wort herbal preparations - Hypericum perforatum (a herbal remedy for depression). Very rarely, Remeron alone or in combination with these medicines may lead to a condition known as serotonin syndrome. Some symptoms of this syndrome include unexplained fever, sweating, increased heart rate, diarrhea, uncontrolled muscle contractions, tremor, hyperactive reflexes, restlessness, mood changes, and loss of consciousness. If a combination of these symptoms occurs, speak to your doctor immediately.
• the antidepressant called nefazodone, which may increase the amount of Remeron in the blood. Inform your doctor if you are taking this medicine, as this may require a reduction in the dose of Remeron or, when nefazodone is discontinued, an increase in the dose of Remeron.
• medicines for anxiety or insomnia, such as benzodiazepines; medicines for schizophrenia, such as olanzapine; medicines for allergies, such as cetirizine; medicines for severe pain, such as morphine. When taken in combination with these medicines, Remeron may increase drowsiness caused by them.
• medicines to treat infections; medicines for bacterial infections (such as erythromycin), medicines for fungal infections (such as ketoconazole), medicines for treating HIV/AIDS (such as HIV protease inhibitors), and medicines for gastric ulcers (such as cimetidine). These medicines, when taken with Remeron, may increase the amount of Remeron in the blood. Inform your doctor if you are taking these medicines. It may be necessary to reduce the dose of Remeron or, when these medicines are discontinued, to increase the dose of Remeron again.
• medicines for epilepsy, such as carbamazepine and phenytoin; medicines for tuberculosis, such as rifampicin. These medicines, when taken with Remeron, may decrease the amount of Remeron in the blood. Inform your doctor if you are taking these medicines. It may be necessary to increase the dose of Remeron or, when these medicines are discontinued, to reduce the dose of Remeron again.
• medicines that prevent blood clotting, such as warfarin. Remeron may enhance the effects of warfarin in the blood. Inform your doctor if you are taking this medicine. If used in combination, your doctor must monitor your blood closely.
• medicines that may affect heart rhythm, such as certain antibiotics and certain antipsychotics.

Remeron with food and alcohol
You may experience drowsiness if you consume alcoholic beverages while taking Remeron.
It is recommended not to consume alcoholic beverages.
Remeron may be taken with or without food.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Limited experience with Remeron administration in pregnant women does not indicate an increased risk. However, caution is advised when administering Remeron during pregnancy.
If you take Remeron up to or immediately before delivery, the newborn must be carefully monitored for possible adverse effects.
When taken during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and appear bluish. These symptoms usually occur within the first 24 hours after birth.
If this happens to your baby, contact your midwife and/or doctor immediately.
Driving and using machines
Remeron may affect your concentration or alertness. Make sure your abilities are not impaired before driving or operating machinery. If your doctor has prescribed Remeron to a patient under 18 years of age, ensure that concentration and alertness are not impaired before engaging in activities such as cycling or other road use.
Remeron orodispersible tablets contain sugar spheres based on sucrose
Remeron orodispersible tablets contain sugar spheres based on sucrose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.
Remeron orodispersible tablets contain aspartame, a source of phenylalanine
This medicine contains aspartame, a source of phenylalanine. Each 15 mg orodispersible tablet contains 4.65 mg of aspartame. Each 30 mg orodispersible tablet contains 9.3 mg of aspartame. This may be harmful if you have phenylketonuria, a rare genetic disorder causing phenylalanine to accumulate because the body cannot properly metabolize it.
Remeron orodispersible tablets contain sodium
This medicine contains less than 1 mmol (23 mg) of sodium per orodispersible tablet, i.e., essentially “sodium-free.”

3. How to take Remeron

Take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
How much Remeron to take
The recommended starting dose is 15 or 30 mg once daily. Your doctor may advise you to increase the
dose after a few days to reach the appropriate amount (between 15 and 45 mg daily). Usually, the dose is the same for all age groups. However, your doctor may adjust the dose if you are elderly or if you have had kidney or liver disease.
When to take Remeron
→ Take Remeron every day at the same time.
It is best to take Remeron as a single dose before going to bed. However, your doctor may
suggest dividing the dose, taking one dose in the morning and one dose in the evening before going to
bed. The higher dose should be taken at bedtime.
How to take the orodispersible tablet as described below
Take the tablets by mouth.

1. Do not break the orodispersible tablet

To prevent breaking the orodispersible tablet, do not press on the tablet imprint on the blister (Figure A).

Fig. A.

2. Detach a tablet imprint

Each blister contains 6 tablets (imprints), separated by perforated lines. Detach one portion by tearing along the perforated lines (Figure 1).

Fig. 1.

3. Lift the cover sheet

Carefully lift the cover sheet, starting from the corner indicated by the arrow (Figures 2
and 3).

Fig. 2.

Fig. 3.

4. Removing the orodispersible tablet

The orodispersible tablet must be removed from its blister with dry hands and placed
on the tongue.
(Figure 4).

Fig. 4.
It will disintegrate rapidly and can be swallowed without water.
When can you expect to feel better?
Remeron usually takes 1–2 weeks to start working, and after 2–4 weeks you may notice an
improvement.
It is important that during the first weeks of treatment you inform your doctor about the effects of Remeron.
→ 2–4 weeks after starting Remeron, discuss with your doctor the effects the medicine has had on you.
If you continue to notice no improvement, your doctor may prescribe a higher dose. In this case, speak to your doctor again after another 2–4 weeks.
Usually, Remeron needs to be taken for 4–6 months after depression symptoms have disappeared.
If you take more Remeron than you should
If you or someone else has taken too much Remeron, contact your doctor immediately.
The most likely signs of an overdose of Remeron (without other medicines or alcohol) are drowsiness,
disorientation, and increased heart rate. Symptoms of a possible overdose may include changes in heart rhythm (fast or irregular heartbeat) and/or fainting, which could be symptoms of a life-threatening condition known as torsade de pointes.
If you forget to take Remeron
If your dose is to be taken once daily

• Do not take a double dose to make up for a forgotten dose. Take the next dose at your usual time.
  If your dose is to be taken twice daily

• If you forget the morning dose, simply take this dose together with the evening dose.

• If you forget the evening dose, do not take it together with the next morning dose; skip the missed dose and continue normally with your morning and evening doses.

• If you have forgotten to take both doses, do not try to make up for the missed doses. Skip both doses and continue normally the next day with your morning and evening doses.

If you stop taking Remeron
→ You should only stop taking Remeron after consulting your doctor.
If you stop treatment too early, depression may return. When you start feeling better, discuss this with your doctor. Your doctor will decide when it is appropriate to stop treatment.
Do not stop taking Remeron suddenly, even if your depression has resolved. If you stop taking Remeron abruptly, you may feel unwell, dizzy, agitated or anxious, and may have headaches. These symptoms can be avoided by stopping treatment gradually. Your doctor will advise you on how to reduce the dose gradually.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If you experience any of the following serious side effects, stop taking mirtazapine and inform your doctor immediately.
Uncommon (may affect up to 1 in 100 people)

• euphoria or emotional excitement (mania).

Rare (may affect up to 1 in 1,000 people)

• yellowing of the eyes or skin; this may indicate liver function disorders (jaundice).

Not known (frequency cannot be estimated from the available data)

• signs of infection such as sudden and unexplained high fever, sore throat, and mouth ulcers (agranulocytosis). In rare cases, mirtazapine may cause disorders in blood cell production (bone marrow depression). Some people may become less resistant to infections because mirtazapine can cause a temporary deficiency of white blood cells (granulocytopenia). In rare cases, mirtazapine may also cause a deficiency of red and white blood cells, and platelets (aplastic anaemia), a deficiency of platelets (thrombocytopenia), or an increase in the number of white blood cells (eosinophilia).
• epileptic seizures (convulsions).
• a combination of symptoms such as unexplained fever, sweating, increased heart rate, diarrhoea, uncontrollable muscle contractions, tremor, hyperactive reflexes, agitation, mood changes, loss of consciousness, and increased salivation. Very rarely, these may be symptoms of serotonin syndrome.
• thoughts of harming yourself or of suicide.
• severe skin reactions:
• reddish spots on the trunk or target-shaped or circular macules, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin eruptions 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 or drug hypersensitivity syndrome).

Other possible side effects with mirtazapine are:
Very common (may affect more than 1 in 10 people)

• increased appetite and body weight
• confusion or drowsiness
• headache
• dry mouth

Common (may affect up to 1 in 10 people)

• lethargy
• dizziness
• tremors
• nausea
• diarrhoea
• vomiting
• constipation
• rash or skin eruptions (exanthema)
• joint pain (arthralgia) or muscle pain (myalgia)
• back pain
• dizziness or fainting when standing up suddenly (orthostatic hypotension)
• swelling (usually in the ankles and feet) caused by fluid retention (oedema)
• fatigue
• vivid dreams
• confusion
• anxiety
• sleep problems
• memory problems, which in most cases resolved after stopping treatment

Uncommon (may affect up to 1 in 100 people)

• abnormal skin sensations, e.g. burning, tingling, itching, or pins and needles (paraesthesia)
• restless legs
• fainting (syncope)
• numbness sensation in the mouth (oral hypoesthesia)
• low blood pressure
• nightmares
• restlessness
• hallucinations
• urge to move

Rare (may affect up to 1 in 1,000 people)

• muscle twitching (myoclonus)
• aggression
• abdominal pain and nausea; this may indicate inflammation of the pancreas (pancreatitis)

Not known (frequency cannot be estimated from the available data)

• abnormal sensation in the mouth (oral paraesthesia)
• swelling in the mouth (mouth oedema)
• swelling throughout the body (generalised oedema)
• localised swelling
• hyponatraemia
• inappropriate secretion of antidiuretic hormone
• severe skin reactions (bullous dermatitis, erythema multiforme)
• night walking (sleepwalking)
• speech disorder
• increased blood levels of creatine kinase
• difficulty urinating (urinary retention)
• muscle pain, stiffness and/or weakness, dark or discoloured urine (rhabdomyolysis)
• increased levels of prolactin hormone in the blood (hyperprolactinaemia, including symptoms of breast enlargement and/or milky discharge from the nipple)
• prolonged and painful penile erection

Additional side effects observed in children and adolescents
In children under 18 years of age, the following side effects were commonly observed in clinical studies: significant weight gain, urticaria, and increased blood triglyceride levels.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco), website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Remeron

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack. The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from light and moisture.
Do not dispose of any medicine via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Remeron contains

• The active substance is mirtazapine. Remeron 15 mg orodispersible tablets contain 15 mg of mirtazapine per orodispersible tablet. Remeron 30 mg orodispersible tablets contain 30 mg of mirtazapine per orodispersible tablet.
• The other components are sugar spheres, hypromellose, povidone K30, magnesium stearate, basic butyl methacrylate copolymer, aspartame (E951), anhydrous citric acid, crospovidone (type A), mannitol (E421), microcrystalline cellulose, natural and artificial orange flavour (No. SN027512), and sodium bicarbonate.

Description of the appearance of Remeron and package contents
Remeron is orodispersible tablets.
Remeron 15 mg orodispersible tablets are round, white tablets with standard bevelled edges, marked on one side with the code “TZ1”.
Remeron 30 mg orodispersible tablets are round, white tablets with standard bevelled edges, marked on one side with the code “TZ2”.
The orodispersible tablets are packaged in child-resistant blisters with perforated unit doses.
The following pack sizes of Remeron 15 mg and 30 mg orodispersible tablets are available: 6, 18, 30, 48, 90, 96 and 180 orodispersible tablets (not all pack sizes may be marketed).

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Organon Italia S.r.l.
Piazza Carlo Magno, 21
00162 Rome, Italy

Manufacturer
N.V. Organon, Kloosterstraat 6, 5349 AB Oss (The Netherlands)

This medicinal product is authorised in the European Economic Area countries under the following names:
Netherlands, Portugal, Romania: Remeron SolTab
Belgium, Luxembourg: Remergon SolTab
Germany: Remergil SolTab
Hungary, Italy: Remeron
Ireland, United Kingdom: Zispin SolTab
Norway, Sweden: Remeron-S
Slovak Republic: Remeron Soltab
Spain: Rexer Flas