MIRTAZAPINE COMBIX 15 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Mirtazapine Combix 15 mg film-coated tablets EFG

Mirtazapine Combix 45 mg film-coated tablets EFG

Read the entire package leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What is Mirtazapine Combix and what is it used for
2. What you need to know before you take Mirtazapine Combix
3. How to take Mirtazapine Combix
4. Possible side effects
5. Storage of Mirtazapine Combix
6. Contents of the pack and further information

1. What is Mirtazapine Combix and what is it used for

Mirtazapine Combix belongs to a group of medicines called antidepressants.

Mirtazapine is used to treat depression in adults.

It may take 1 to 2 weeks before mirtazapine starts to work. After 2 to 4 weeks, you may start to feel better. You should see your doctor if you feel no improvement or if you feel worse after 2 to 4 weeks.

For more information, see section 3 "When can you expect to feel better".

2. What you need to know before you take Mirtazapine Combix

Do not takeMirtazapine Combix

• if you are allergic to mirtazapine or any of the other ingredients of this medicine (listed in section 6). If so, contact your doctor as soon as possible before taking mirtazapine.
• if you are taking or have taken in the last two weeks medicines called monoamine oxidase inhibitors (MAOIs).

Warnings and precautions

Talk to your doctor or pharmacist before starting to take mirtazapine.

Tell your doctor before taking Mirtazapine Combix:

If you have ever had a severe skin rash or peeling of the skin, blisters or sores in the mouth after taking mirtazapine.

Children and adolescents

Mirtazapine should not normally be used for the treatment of children and adolescents under 18 years. Mirtazapine has not been shown to be effective in children and adolescents. Also, patients under 18 are at increased risk of side effects such as suicide attempt, suicidal thoughts, and hostility (predominantly aggression, oppositional behavior, and anger) when they take this type of medicine. Nevertheless, your doctor may prescribe mirtazapine for patients under 18 when it is decided that it is the best option for the patient. If your doctor has prescribed mirtazapine to a patient under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the above symptoms occur or worsen in patients under 18 taking mirtazapine. Furthermore, the long-term safety of mirtazapine on growth, maturation, and cognitive and behavioral development in this age group has not been established. Weight gain was also observed more frequently in this age group when treated with mirtazapine compared to adults.

Suicidal thoughts and worsening of depression

If you are depressed, you may sometimes have thoughts of harming or killing yourself. These thoughts may be worse when you first start taking antidepressants, as these medicines take time to work, usually 2 weeks or more.

You may be more likely to think this way if:

• you have previously had thoughts of self-harm or suicide.
• you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

→ If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

It may be helpful to tell a relative or close friendthat you are depressed and ask them to read this package leaflet. You might ask them to tell you if they think your depression is getting worse, or if they are worried about changes in your behavior.

Also, be careful with mirtazapine

• if you have or have had any of the following conditions:

→ Tell your doctor about these conditions before taking mirtazapine, if you have not already done so

• seizures(epilepsy). If seizures occur or become more frequent, stop taking mirtazapine and contact your doctor immediately;
• liver disease, including jaundice. If jaundice occurs, stop taking mirtazapine and contact your doctor immediately;
• kidney disease;
• heart diseaseor low blood pressure;
• schizophrenia. If psychotic symptoms, such as paranoid thoughts, become more frequent or severe, contact your doctor immediately;
• bipolar depression(alternating periods of overactivity/manic behavior and periods of depression). If you start to feel overactive or elated, stop taking mirtazapine and contact your doctor immediately;
• diabetes(you may need to adjust your insulin or other antidiabetic medicines);
• eye diseases, such as increased pressure in the eye (glaucoma);
• difficulty urinating, which may be due to an enlarged prostate;
• certain types of heart diseasethat can change the rhythm of your heart, a recent heart attack, heart failure, or taking certain medicines that can affect the heart rhythm.

• if signs of infection such as high, unexplained fever, sore throat, and mouth ulcers appear

→ Stop taking mirtazapine and contact your doctor immediately for a blood test.

In rare cases, these symptoms can be signs of changes in blood cell production in the bone marrow. Although rare, these symptoms usually occur within 4-6 weeks of treatment.

• if you are an elderly person. You may be more sensitive to the side effects of antidepressant medicines.
• serious skin reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of mirtazapine. Stop taking mirtazapine and seek medical attention immediately if you notice any of the symptoms described in section 4 related to these serious skin reactions.

If you have ever had a serious skin reaction, do not restart treatment with mirtazapine.

Other medicines and Mirtazapine Combix

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Mirtazapine Combixwith:

• monoamine oxidase inhibitors (MAOIs). Also, do not take mirtazapine during the two weeks after you stop taking MAOIs. If you stop taking mirtazapine, do not take MAOIs during the following two weeks.

Examples of MAOIs are moclobemide, tranylcypromine (both are antidepressants), and selegiline (for Parkinson's disease).

Be carefulifyou take mirtazapine with:

• antidepressants such as selective serotonin reuptake inhibitors (SSRIs),venlafaxine, and L-tryptophan or triptans(used to treat migraine), tramadol(for pain), linezolid(an antibiotic), lithium(used to treat certain psychiatric disorders), methylene blue(used to treat high levels of methemoglobin in the blood), and St. John's Wort (Hypericum perforatum)(a herbal remedy for depression). In rare cases, mirtazapine alone or with these medicines may cause a condition called serotonin syndrome. Some of the symptoms of this syndrome are: unexplained fever, sweating, palpitations, diarrhea, muscle contractions (involuntary), shivering, exaggerated reflexes, restlessness, mood changes, and loss of consciousness. If you have a combination of these symptoms, contact your doctor immediately.
• the antidepressant nefazodone. It may increase the amount of mirtazapine in your blood. Tell your doctor if you are taking this medicine. Your doctor may need to decrease the dose of mirtazapine or increase it again when you stop taking nefazodone.
• medicines for anxiety or insomniasuch as benzodiazepines.
• medicines for schizophreniasuch as olanzapine.
• medicines for allergiessuch as cetirizine.
• strong painkillers such as morphine.

When taken with these medicines, mirtazapine may increase the drowsiness caused by these medicines.

• medicines for infections:medicines for bacterial infections (such as erythromycin), medicines for fungal infections (such as ketoconazole), and medicines for HIV/AIDS (HIV protease inhibitors) and medicines for stomach ulcers (such as cimetidine).

If taken with mirtazapine, these medicines may increase the amount of mirtazapine in your blood. Tell your doctor if you are taking these medicines. Your doctor may need to decrease the dose of mirtazapine or increase it again when you stop taking these medicines.

• medicines for epilepsysuch as carbamazepine and phenytoin;
• medicines for tuberculosissuch as rifampicin.

If taken with mirtazapine, these medicines may decrease the amount of mirtazapine in your blood. Tell your doctor if you are taking these medicines. Your doctor may need to increase the dose of mirtazapine or decrease it again when you stop taking these medicines.

• medicines to prevent blood clottingsuch as warfarin.

Mirtazapine may increase the effects of warfarin on the blood. Tell your doctor if you are taking this medicine. If taken together, your doctor may recommend that you have regular blood tests.

• medicines that may affect the heart rhythm, such as certain antibiotics and some antipsychotics.

Taking Mirtazapine Combix with food and alcohol

You may feel drowsy if you drink alcohol while taking mirtazapine.

It is recommended not to drink alcohol.

You can take mirtazapine with or without food.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Limited experience with mirtazapine administration to pregnant women does not indicate an increased risk. However, caution should be exercised when used during pregnancy.

If you use mirtazapine up to or shortly before birth, your baby will be checked for possible adverse effects.

When taken during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition called persistent pulmonary hypertension in newborns (PPHN) in babies, which makes the baby breathe faster and turn blue. These symptoms usually start during the first 24 hours after birth. If this happens to your baby, you should contact your midwife and/or doctor immediately.

Driving and using machines

Mirtazapine may affect your concentration or alertness. Make sure your abilities are not affected before driving or using machinery. If your doctor has prescribed mirtazapine for a patient under 18, make sure their concentration and alertness are not affected before cycling (for example).

Mirtazapine Combix contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Mirtazapine Combix

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

How much to take

The recommended initial dose is 15 or 30 mg per day. Your doctor may recommend that you increase your dose after a few days to the amount that is best for you (between 15 and 45 mg per day). The dose is usually the same for all ages. However, if you are an elderly person or have kidney or liver disease, your doctor may change the dose.

When to take it

→ Take mirtazapine at the same time each day.

It is best to take the dose of mirtazapine once before going to bed. However, your doctor may recommend that you divide your dose of mirtazapine in the morning and before going to bed. The highest dose should be taken before going to bed.

The tablets are taken orally. Take the prescribed dose of mirtazapine without chewing, with water or juice.

When can you expect to feel better

Normally, mirtazapine will start to work after 1 or 2 weeks, and after 2 to 4 weeks, you may start to feel better.

It is important that during the first few weeks of treatment, you talk to your doctor about the effects of mirtazapine:

→ between 2 and 4 weeks after you start taking mirtazapine, talk to your doctor about how this medicine has affected you.

If you still do not feel better, your doctor may prescribe a higher dose. In that case, talk to your doctor again after another 2-4 weeks.

Normally, you will need to take mirtazapine until the symptoms of depression have disappeared for 4-6 months.

If you take more Mirtazapine Combix than you should

→ If you or someone else has taken too much mirtazapine, contact a doctor immediately.

The most likely symptoms of a mirtazapine overdose (without other medicines or alcohol) are drowsiness, disorientation, and palpitations. The symptoms of a possible overdose may include changes in the rhythm of your heart (fast, irregular heartbeat) and/or fainting, which could be symptoms of a potentially life-threatening condition known as Torsades de pointes.

You can also contact the Toxicology Information Service. Telephone 91 562 04 20.

If you forget to take Mirtazapine Combix

If you have to take your dose once a day.

• Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time.

If you have to take your dose twice a day.

• if you have forgotten the morning dose, simply take it with the evening dose.
• if you have forgotten the evening dose, do not take it the next morning; skip it and continue with your normal doses in the morning and evening.
• if you have forgotten both doses, do not try to make them up. Skip both doses and the next day continue with your normal dose in the morning and evening.

If you stop taking Mirtazapine Combix

→ Only stop taking mirtazapine after talking to your doctor.

If you stop too early, your depression may come back. When you feel better, talk to your doctor. Your doctor will decide when you can stop treatment.

Do not stop taking mirtazapine abruptly, even if your depression has disappeared. If you stop taking mirtazapine suddenly, you may feel unwell, dizzy, agitated, or anxious, and have headaches. These symptoms can be avoided by gradually stopping treatment. Your doctor will tell you how to gradually decrease the dose.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If you experience any of the following serious adverse effects, stop taking mirtazapine and immediately inform your doctor.

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

• feeling of exaggerated euphoria (mania).

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

• yellowing of the eyes or skin; may suggest liver function alterations (jaundice).
• Frequency not known (cannot be estimated from available data):
• signs of infection such as high, unexplained, and sudden fever, sore throat, and sores in the mouth (agranulocytosis). In rare cases, mirtazapine can cause alterations in blood cell production (bone marrow depression). Some people become less resistant to infections because mirtazapine can cause a temporary decrease in white blood cells (granulocytopenia). In rare cases, mirtazapine can also cause a decrease in red and white blood cells and platelets (aplastic anemia), a decrease in platelets (thrombocytopenia), or an increase in the number of white blood cells in the blood (eosinophilia).
• epileptic seizure (convulsions).
• combination of symptoms such as unexplained fever, sweating, palpitations, diarrhea, muscle contractions (involuntary), chills, exaggerated reflexes, agitation, mood changes, loss of consciousness, and increased saliva production. In very rare cases, these symptoms can be signs of a disorder called "serotonin syndrome".
• thoughts of self-harm or suicide.
• severe skin reactions:
• • red patches on the torso, such as circumscribed or circular spots, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin eruptions can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • generalized erythema, elevated body temperature, and enlarged lymph nodes (DRESS or drug hypersensitivity syndrome).

Other possible adverse effects with mirtazapine are:

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

• increased appetite and weight gain
• drowsiness
• headache
• dry mouth

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

• lethargy
• dizziness
• tremors
• nausea
• diarrhea
• vomiting
• constipation
• urticaria or skin eruptions (exanthema)
• joint pain (arthralgia) or muscle pain (myalgia)
• back pain
• dizziness or fainting when standing up quickly (orthostatic hypotension)
• swelling (usually in ankles or feet) due to fluid retention (edema)
• fatigue
• vivid dreams
• confusion
• anxiety
• difficulty sleeping
• memory problems, which in most cases resolved when treatment was discontinued

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

• strange sensation in the skin, such as burning, pinching, tingling, or numbness (paresthesia)
• involuntary leg movements during sleep
• fainting (syncope)
• numbness in the mouth (oral hypoesthesia)
• low blood pressure
• nightmares
• agitation
• hallucinations
• inability to remain still

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

• tics or muscle contractions (myoclonus)
• aggression
• abdominal pain, nausea; this may indicate pancreas inflammation (pancreatitis)

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

• abnormal sensations in the mouth (oral paresthesia)
• swelling in the mouth (oral edema)
• swelling throughout the body (generalized edema)
• localized swelling
• hyponatremia
• inadequate secretion of antidiuretic hormone
• severe skin reactions (bullous dermatitis, erythema multiforme)
• sleepwalking (somnambulism)
• speech problems
• increased creatine kinase levels in the blood
• difficulty urinating (urinary retention)
• muscle pain, stiffness, and/or weakness, darkening or discoloration of urine (rhabdomyolysis)
• increased prolactin hormone levels in the blood (hyperprolactinemia, including symptoms of breast enlargement and/or milky discharge from the nipple)
• painful and prolonged erection of the penis.

Other adverse effects in children and adolescents

In patients under 18 years of age, the following adverse effects were frequently observed in clinical trials: significant weight gain, urticaria, and increased triglycerides in the blood.

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Mirtazapine Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the box and on the blister pack after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Mirtazapine Combix

• The active ingredient is mirtazapine.

Mirtazapine Combix 15 mg film-coated tablets contain 15 mg of mirtazapine per tablet.

Mirtazapine Combix 45 mg film-coated tablets contain 45 mg of mirtazapine per tablet.

• The other components (excipients) are:

Core of the tablet: cornstarch, anhydrous colloidal silica, magnesium stearate, hydroxypropylcellulose, and lactose monohydrate.

Coating of the Mirtazapine Combix 15 mg tablet: yellow coating agent (titanium dioxide (E171), yellow iron oxide (E172), hypromellose, and macrogol).

Coating of the Mirtazapine Combix 45 mg tablet: white coating agent (titanium dioxide (E171), hypromellose, and macrogol).

Appearance of the product and package contents

Mirtazapine Combix are film-coated tablets.

Mirtazapine Combix 15 mg film-coated tablets EFG

The tablets are yellow or yellowish, biconvex, oval, coated, scored on one side, engraved with "M" on one side of the score and "5" on the other side of the score, smooth on the other side, and have approximate dimensions of 10.2 mm in length and 5.2 mm in width.

The tablet can be divided into equal doses.

The tablets are packaged in blister packs, in packs of 30 or 60 tablets.

Mirtazapine Combix 45 mg film-coated tablets EFG

The tablets are white or whitish, biconvex, oval, coated, marked on one side with "M7", smooth on the other, and have approximate dimensions of 14.1 mm in length and 7.6 mm in width.

The tablets are packaged in blister packs, in packs of 30 tablets.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón

(Madrid) Spain

Manufacturer

Emona Biopharma d.o.o.,

PE WTC Dunajska cesta 156

1000 Ljubljana,

Slovenia

Date of the last revision of this prospectus: January 2025

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/