Mirtazapine Combix 30 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Mirtazapina Combix 30 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, 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 such effects are not listed in this leaflet. See section 4.

Leaflet contents

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

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

Mirtazapine Combix belongs to a group of medicines called antidepressants.

Mirtazapine is used to treat depression.

2. What you need to know before taking Mirtazapine Combix

Do not take Mirtazapine Combix

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if you are taking or have recently taken (within the last two weeks) medicines called monoamine oxidase inhibitors (MAOIs).
• if you have ever experienced a severe skin rash, skin peeling, blisters, or mouth sores after taking mirtazapine or other medicines.

Warnings and precautions

Talk to your doctor or pharmacist before starting to take Mirtazapine Combix.

Children and adolescents (under 18 years of age)

Mirtazapine Combix is not normally used to treat children and adolescents under 18 years of age. You should also be aware that in patients under 18 years of age, there is an increased risk of adverse effects such as suicide attempts, suicidal ideation, and hostility (predominantly aggression, confrontation behavior, and irritability) when taking this type of medicine. Nevertheless, your doctor may prescribe Mirtazapine Combix to patients under 18 years of age if they decide it is the most appropriate treatment. If your doctor has prescribed Mirtazapine Combix to a patient under 18 years of age and you wish to discuss this decision, please contact your doctor again. You must inform your doctor if any of the symptoms listed above appear or worsen in patients under 18 years of age who are taking Mirtazapine Combix. In addition, the long-term effects on safety related to growth, maturation, and cognitive and behavioral development of mirtazapine in this age group are still not fully known.

Suicidal thoughts and worsening depression

If you are depressed, you may sometimes have thoughts about harming yourself or committing suicide. This may worsen when you first start taking antidepressants, as these medicines usually take up to two weeks, or sometimes longer, to take effect.

You may be more likely to have such thoughts if:

• you have previously had suicidal thoughts or thoughts about 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 committing 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, take special care with Mirtazapine Combix

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

• Inform your doctor about these conditions before taking Mirtazapine Combix, 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 occurs, 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 (alternating periods of elevated mood/hyperactivity and 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 medicines);

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

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

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

• Stop taking Mirtazapine Combix and contact your doctor immediately to have a blood test.

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

• if you are elderly, you may be more sensitive to the adverse 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 mirtazapine use. Discontinue use and seek immediate medical attention if you notice any of the symptoms described in section 4 related to these serious skin reactions.
• if you have ever experienced serious skin reactions, treatment with mirtazapine should not be restarted.

Taking Mirtazapine Combix with other medicines

Also inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine.

Tell your doctor or pharmacist if you are taking (or plan to take) any of the medicines listed below.

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 at least the next two weeks.

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

Be cautious if you take Mirtazapine Combix together with:

• antidepressants such as serotonin reuptake inhibitors (SSRIs), venlafaxine and L-tryptophan or triptans (used for migraine), tramadol (for pain), linezolid (an antibiotic), lithium (used to treat certain psychiatric disorders), and St. John's wort – Hypericum perforatum (a 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 your 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 together with these medicines, mirtazapine may increase the drowsiness caused by them.

• medicines for infections: antibiotics (such as erythromycin), antifungal medicines (such as ketoconazole), and medicines for HIV/AIDS (HIV protease inhibitors).

If taken together with mirtazapine, these medicines may increase the amount of mirtazapine in your 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 your 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 increase the effects of warfarin on the blood. Inform your doctor if you are taking this medicine. If taken together, your doctor should monitor your blood regularly.

Taking Mirtazapine Combix with food, drinks, and alcohol

You may feel drowsy if you drink alcohol while being treated with mirtazapine.

It is recommended not to drink any alcohol.

You may take mirtazapine with or without food.

Pregnancy, breastfeeding, and fertility

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

Consult your doctor or pharmacist before using any medicine.

Limited experience with the administration of Mirtazapine Combix to pregnant women does not indicate an increased risk. However, caution should be exercised if used during pregnancy.

If you are taking mirtazapine and become pregnant or wish to become pregnant, consult your doctor about whether you can continue taking mirtazapine. If you take mirtazapine up to or shortly before delivery, your baby will be examined for possible adverse effects.

Consult your doctor about whether you can breastfeed while taking Mirtazapine Combix.

If you are taking Mirtazapine Combix during pregnancy, inform your midwife and/or doctor. When similar medicines (called serotonin reuptake inhibitor antidepressants: SSRIs) are taken during pregnancy, there may be an increased risk of the baby developing a serious condition called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and appear blue. These symptoms usually begin within the first 24 hours after birth. If this occurs in your case, contact a doctor and/or midwife immediately.

Driving and using machines

During treatment with Mirtazapine Combix, you may feel drowsy or dizzy. Do not drive or operate tools or machinery until you know how this treatment affects you.

Mirtazapine Combix 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 in doubt, consult your doctor or pharmacist again.

How much to take

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

When to take it

• Take Mirtazapine Combix at the same time each day.

It is best to take the mirtazapine dose as a single dose before going to bed. However, your doctor may recommend splitting your mirtazapine dose into a morning and an evening dose, with the higher dose taken before bedtime.

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

When you can expect to feel better

Mirtazapine Combix usually starts to take effect after 1 or 2 weeks, and after 2 to 4 weeks you may start to feel better. It is important that during the first weeks of treatment you discuss the effects of mirtazapine with your doctor.

• 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 to your doctor again after another 2–4 weeks.

You will usually 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 Combix, consult a doctor immediately.

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

The most likely symptoms of an overdose of mirtazapine (without other medicines or alcohol) are drowsiness, confusion, and palpitations.

If you forget to take Mirtazapine Combix

If you are supposed to take your dose once daily

• if you forget to take your dose of mirtazapine, do not take the missed dose. Skip it and take your usual dose the next day.

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 if advised by 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 gradually reduce the dose.

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

4. Possible adverse effects

Like all medicines, Mirtazapine Combix may produce adverse effects, although not everyone experiences them.

Some adverse effects are more likely than others. The possible adverse effects of mirtazapine are listed below and can be categorized as follows:

• Very common: affect more than 1 in 10 patients
• Common: affect 1 in 100 patients
• Uncommon: affect between 1 and 10 in 1,000 patients
• Rare: affect between 1 and 10 in 10,000 patients
• Very rare: affect fewer than 1 in 10,000 patients
• Not known: cannot be estimated from available data

Very common:

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

Common:

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

Uncommon:

• feeling of exaggerated euphoria (mania)

• Stop taking mirtazapine and consult your doctor immediately.

• • unusual skin sensations such as burning, pricking, tingling or numbness (paraesthesia)
  • involuntary restless leg movements during sleep
  • fainting (syncope)
  • numbness of the mouth (oral hypoesthesia)
  • low blood pressure
  • nightmares
  • restlessness
  • hallucinations
  • inability to remain still

Rare:

• yellowing of the eyes or skin; may indicate liver dysfunction (jaundice)

• Stop taking mirtazapine and consult your doctor immediately.

  • muscle tics or contractions (myoclonus)
  • pancreatitis

Not known:

• signs of infection such as sudden unexplained fever, sore throat and mouth ulcers (agranulocytosis)

• Stop taking mirtazapine and consult your doctor immediately for a blood test.

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 anaemia), a decrease in platelets (thrombocytopenia), or an increase in the number of white blood cells in the blood (eosinophilia).

• epileptic seizure (convulsions)

• Stop taking mirtazapine and consult your doctor immediately.

  • combination of symptoms such as unexplained fever, sweating, palpitations, diarrhoea, uncontrollable muscle contractions, chills, exaggerated reflexes, agitation, mood changes and loss of consciousness. In very rare cases, these symptoms may indicate a disorder known as "serotonin syndrome".

• Stop taking mirtazapine and consult your doctor immediately.

  • thoughts of harming yourself or of suicide

• Stop taking mirtazapine and consult your doctor immediately.

  • abnormal sensations in the mouth (oral paraesthesia)
  • swelling of the mouth (oral oedema)
  • hyponatraemia
  • inappropriate secretion of antidiuretic hormone
  • red patches on the trunk, appearing as circumscribed or circular macules, often with blisters in the centre, skin peeling, and ulcers in the mouth, throat, nose, genitals and eyes. These serious 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)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: 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 packaging 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 or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of containers and medicines 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 30 mg film-coated tablets contain 30 mg of mirtazapine per tablet.

• The other components are:

Tablet core: maize starch, colloidal silicon dioxide, magnesium stearate (E470b), hydroxypropylcellulose (E463), and lactose monohydrate.

Tablet coating: titanium dioxide (E171), hypromellose (E464), yellow iron oxide (E172), black iron oxide (E172), red iron oxide (E172), and polyethylene glycol 8000.

Appearance of the product and contents of the pack

Mirtazapine Combix are film-coated tablets.

Mirtazapine Combix film-coated tablets are beige, oval-shaped, and have a score line on one side.

The tablet can be divided into equal halves.

Mirtazapine Combix 30 mg film-coated tablets are packaged in blister packs.

The following pack sizes are available: 30 tablets.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Combino Pharm Malta Ltd.

HF 60 HAL FAR Industrial Estate

HAL FAR BBG07-

MALTA

or

ZYDUS FRANCE

Zac Les Hautes Pâtures

Parc d'Activités des Pleupliers

25 rue des Pleupliers

92000 Nanterre (France)

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the most recent review of this leaflet: September 2020

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