Mirtazapine Combix 15 mg film-coated tablets EFG

Package leaflet: Information for the user

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 leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Mirtazapina Combix belongs to a group of medicines called antidepressants.

Mirtazapine is used to treat depression in adults.

It takes 1 to 2 weeks before mirtazapine starts to take effect. After 2 to 4 weeks, you may begin to feel better. You should consult your doctor if your condition worsens or does not improve after 2 to 4 weeks.

For more information, see section 3, "When can you expect to start feeling better?"

2. What you need to know before taking Mirtazapine Combix

Do not take Mirtazapine Combix

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

Warnings and precautions

Talk to your doctor or pharmacist before taking mirtazapine.

Tell your doctor before taking Mirtazapine Combix:

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

Children and adolescents

Mirtazapine should normally not be used in the treatment of children and adolescents under 18 years of age because its efficacy has not been demonstrated. At the same time, you should know that in patients under 18 years of age there is an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (mainly aggression, confrontation behavior, and irritability) when taking this type of medication. Nevertheless, your doctor may prescribe mirtazapine to patients under 18 years of age if they decide it is best for the patient. If your doctor has prescribed mirtazapine to a patient under 18 years of age and you wish to discuss this decision, please return to your doctor. You must inform your doctor if any of the symptoms described above appear or worsen in patients under 18 years of age who are taking mirtazapine. In addition, the long-term safety effects related to growth, maturation, and cognitive and behavioral development of mirtazapine in this age group are still unknown. A considerable weight gain has also been 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 yourself or of suicide. This may worsen when you first start taking antidepressants, as these medicines usually take time to work—typically two weeks or sometimes longer.

You may be more likely to have such thoughts if:

• you have previously had suicidal thoughts or thoughts of self-harm.
• you are a young adult. Clinical trial data have shown an increased risk of suicidal behavior in adults under 25 years of age with psychiatric disorders who are being treated with an antidepressant.

→ If at any time you have thoughts of harming yourself or of suicide, consult your doctor or go to a hospital immediately.

It may be helpful to tell a close family member or friend that you are depressed and ask them to read this leaflet. You may ask them to inform you if they think your depression is getting worse or if they are concerned about changes in your behavior.

Also, be especially careful with mirtazapine

• if you have or have ever had one of the following conditions:

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

• seizures (epilepsy). If seizures occur or your seizures become more frequent, stop taking mirtazapine and contact your doctor immediately;

• liver disease, including jaundice. If jaundice appears, stop taking mirtazapine 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;

• bipolar depression (periods of elevated mood/hyperactivity alternate with periods of depression). If you start feeling elated or overexcited, stop taking mirtazapine and contact your doctor immediately;

• diabetes (you may need to adjust your insulin dose or other antidiabetic medications);

• eye diseases, such as increased pressure in the eye (glaucoma);

• difficulty urinating, which could be due to an enlarged prostate;

• certain types of heart disease that may alter your heart rhythm, a recent heart attack, heart failure, or if you are taking certain medications that may affect heart rhythm.

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

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

Rarely, these symptoms may indicate disturbances in blood cell production in the bone marrow. Although rare, these symptoms typically appear 4–6 weeks after starting treatment.

• if you are an elderly person. You may be more sensitive to the adverse effects of antidepressant medicines.
• severe 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. Discontinue use and seek immediate medical attention if you notice any of the symptoms described in section 4 related to these severe skin reactions.

If you have ever had severe skin reactions, treatment with mirtazapine should not be restarted.

Other medicines and Mirtazapine Combix

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

Do not take Mirtazapine Combix together with:

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

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

Be careful if you take mirtazapine together 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 preparations – Hypericum perforatum (herbal remedy for depression). In very rare cases, mirtazapine alone or in combination with these medicines may lead to a condition called serotonin syndrome. Some symptoms of this syndrome include: unexplained fever, sweating, palpitations, diarrhea, uncontrollable muscle contractions, chills, exaggerated reflexes, agitation, mood changes, and loss of consciousness. If you experience a combination of these symptoms, consult your doctor immediately.
• the antidepressant nefazodone. This may increase the amount of mirtazapine in the blood. Inform your doctor if you are taking this medicine. It may be necessary to reduce the dose of mirtazapine, or increase it again when stopping nefazodone.
• 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, mirtazapine may increase the drowsiness caused by them.

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

If taken together with mirtazapine, these medicines may increase the amount of mirtazapine in the blood. Inform your doctor if you are taking these medicines. It may be necessary to reduce the dose of mirtazapine, or increase it again when stopping these medicines.

• medicines for epilepsy such as carbamazepine and phenytoin;
• medicines for tuberculosis such as rifampicin.

If taken together with mirtazapine, these medicines may reduce the amount of mirtazapine in the blood. Inform your doctor if you are taking these medicines. It may be necessary to increase the dose of mirtazapine, or decrease it again when stopping these medicines.

• medicines to prevent blood clotting such as warfarin.

Mirtazapine may enhance the effects of warfarin on the blood. Inform your doctor if you are taking this medicine. If taken together, it is recommended that your doctor perform regular blood tests.

• medicines that may affect 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 any alcohol.

You may take mirtazapine with or without food.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

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

If you take mirtazapine up to or shortly before delivery, your baby will be examined for possible adverse effects.

Antidepressants similar to mirtazapine (SSRIs) taken during pregnancy may increase the risk of newborns developing a serious condition called persistent pulmonary hypertension of the newborn (PPHN), which causes the baby to breathe faster and appear bluish. These symptoms usually begin within the first 24 hours after birth. If this happens to your baby, consult your midwife and/or doctor immediately.

Driving and using machines

Mirtazapine may affect your concentration or alertness. Make sure your abilities are not impaired before driving or operating machinery. If your doctor has prescribed mirtazapine to a patient under 18 years of age, ensure that concentration and alertness are not affected before engaging in activities such as cycling.

Mirtazapine Combix contains lactose

This medicine contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult with them before taking this medicine.

3. How to take Mirtazapine Combix

Follow exactly the instructions for using this medicine as given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

How much to take

The recommended starting dose is 15 or 30 mg once daily. Your doctor may recommend increasing your dose after a few days to the amount that is best for you (between 15 and 45 mg per day). Usually, the dose is the same for all age groups. However, if you are elderly or have kidney or liver disease, your doctor may adjust your dose.

When to take it

→ Take mirtazapine at the same time each day.

It is best to take the dose of mirtazapine as a single dose before going to bed. However, your doctor may advise you to divide your dose, taking part in the morning and part at night before going to bed. The higher dose should be taken at night before going to bed.

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

When you can expect to feel better

Mirtazapine usually starts to work after 1 or 2 weeks, and after 2 to 4 weeks you may begin to feel better.

It is important that during the first weeks of treatment you speak with your doctor about the effects of mirtazapine:

→ 2 to 4 weeks after starting 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, speak with your doctor again after another 2–4 weeks.

Usually, you will need to take mirtazapine until depressive symptoms have been absent for 4–6 months.

If you take more Mirtazapine Combix than you should

→ If you or someone else takes too much mirtazapine, consult a doctor immediately.

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

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

If you forget to take Mirtazapine Combix

If you are supposed to take your dose once daily:

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

If you are supposed to take your dose twice daily:

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

If you stop taking Mirtazapine Combix

→ Stop taking mirtazapine only after consulting your doctor.

If you stop too early, depression may return. When you start feeling better, talk to your doctor. Your doctor will decide when you can stop treatment.

Do not stop taking mirtazapine abruptly, even if depression has resolved. If you stop mirtazapine suddenly, 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 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 everyone will experience them.

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

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; this may indicate liver problems (jaundice).

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

• signs of infection such as unexplained high fever, sudden sore throat, and mouth ulcers (agranulocytosis). In rare cases, mirtazapine may cause disturbances in blood cell production (bone marrow depression). Some people become less resistant to infections because mirtazapine may cause a temporary decrease in white blood cells (granulocytopenia). In rare cases, mirtazapine may also cause a decrease in red blood cells, 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, uncontrollable muscle contractions, chills, exaggerated reflexes, agitation, mood changes, loss of consciousness, and increased saliva production. In very rare cases, these symptoms may be signs of a disorder called "serotonin syndrome."
• thoughts of harming yourself or of suicide.
• severe skin reactions:
  • red patches on the trunk, such as well-defined or circular macules, often with blisters in the center, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • generalized erythema, elevated body temperature, and enlarged lymph nodes (DRESS syndrome 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
• tremor
• nausea
• diarrhea
• vomiting
• constipation
• hives or skin rash (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):

• unusual sensations in the skin such as burning, prickling, tingling, or numbness (paresthesia)
• involuntary restless leg movements during sleep
• fainting (syncope)
• numbness sensation 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 inflammation of the pancreas (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
• inappropriate antidiuretic hormone secretion
• severe skin reactions (bullous dermatitis, erythema multiforme)
• sleepwalking (somnambulism)
• speech disorder
• increased levels of creatine kinase in the blood
• difficulty urinating (urinary retention)
• muscle pain, stiffness and/or weakness, darkening or discoloration of urine (rhabdomyolysis)
• increased levels of prolactin hormone in the blood (hyperprolactinemia, including symptoms such as breast enlargement and/or milky nipple discharge)
• painful and prolonged penile erection.

Other adverse effects in children and adolescents

In patients under 18 years of age, the following adverse effects were frequently observed in clinical trials: marked weight gain, hives, and increased blood triglyceride levels.

Reporting of adverse effects

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

5. Storage of Mirtazapine Combix

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 after EXP.. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Medicines must not be disposed of via wastewater drains or household waste. Dispose of unused medicines and their containers at the SIGRE Point in your pharmacy. If you have any doubts, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Mirtazapine Combix

• The active substance is mirtazapine.

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

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

• The other components (excipients) are:

Tablet core: maize starch, anhydrous colloidal silica, magnesium stearate, hydroxypropylcellulose and monohydrate lactose.

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

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

Appearance of the product and contents of the pack

Mirtazapine Combix are film-coated tablets.

Mirtazapine Combix 15 mg film-coated tablets EFG

The tablets are yellow or yellowish in colour, biconvex, oval, film-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, with 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 packed in blisters, in packs of 30 or 60 tablets.

Mirtazapine Combix 45 mg film-coated tablets EFG

The tablets are white or almost white, biconvex, oval, film-coated, marked on one side with “M7”, smooth on the other side, with approximate dimensions of 14.1 mm in length and 7.6 mm in width.

The tablets are packed in blisters, in packs of 30 tablets.

Marketing Authorisation 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 most recent revision of this leaflet: January 2025

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