MIRTAZAPINE COMBIX 30 mg FILM-COATED TABLETS

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

Do not take Mirtazapine Combix

• if you are allergicto the active substance or any of the other ingredients of this medicine (listed in section 6).
• if you are taking or have taken in the last two weeks medicines called monoamine oxidase inhibitors (MAOIs).
• if you have ever suffered from a severe skin rash or blistering of the skin, mouth, or eyes after taking mirtazapine or other medicines.

Warnings and precautions

Consult your doctor or pharmacist before taking Mirtazapine Combix.

Children and adolescents (under 18 years)

Mirtazapine Combix should not normally be used in the treatment of children and adolescents under 18 years. At the same time, you should know that in patients under 18 years, there is an increased risk of side effects such as suicidal attempts, suicidal thoughts, and hostility (mainly aggression, confrontational behavior, and irritation) when taking this class of medicines. Nevertheless, your doctor may prescribe Mirtazapine Combix to patients under 18 years when they decide it is most convenient for the patient. If your doctor has prescribed Mirtazapine Combix to a patient under 18 years and you want to discuss this decision, please go back to your doctor. You should inform your doctor if any of the above symptoms appear or worsen in patients under 18 years who are taking Mirtazapine Combix. Additionally, the long-term safety effects related to growth, maturity, and development of knowledge and behavior of mirtazapine in this age group are not yet known.

Suicidal thoughts and worsening of depression

If you are depressed, you may sometimes have thoughts of harming or killing yourself. This may worsen when you first start taking antidepressants, as these medicines may take two weeks or sometimes longer to work.

You may be more likely to think this way if:

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

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

It may be helpful to tell a relative or close friendthat you are depressed and ask them to read this leaflet. You can 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 very careful with Mirtazapine Combix

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

• Tell your doctor about these situations before taking Mirtazapine Combix, if you have not already:

• 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 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 excitement/hyperactivity and periods of depression). If you start to feel excited or overexcited, stop taking mirtazapine and contact your doctor immediately;
• diabetes(you may need to adjust your insulin or other antidiabetic medication dose);
• eye diseases, 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 high unexplained fever, sore throat, and mouth ulcers

• Stop taking Mirtazapine Combix and contact your doctor immediately to have 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 appear 4-6 weeks after treatment starts.

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

Using Mirtazapine Combix with other medicines

Also, tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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

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 careful ifyou take Mirtazapine Combix with:

• antidepressants such as selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and L-tryptophan or triptans(used for migraine), tramadol(for pain), linezolid(an antibiotic), lithium(used to treat some psychiatric disorders), 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 symptoms of this syndrome are: unexplained fever, sweating, palpitations, diarrhea, muscle contractions (involuntary), shivering, exaggerated reflexes, agitation, mood changes, and loss of consciousness). If you experience 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.

medicines for severe painsuch 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).

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 in the blood. Tell your doctor if you are taking this medicine. If taken together, your doctor may recommend that you have blood tests.

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 can take mirtazapine with or without food.

Pregnancy, breastfeeding, and fertility

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.

Consult your doctor or pharmacist before taking any medicine.

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

If you are taking mirtazapine and become pregnant or want to become pregnant, consult your doctor if you can continue taking mirtazapine. If you use mirtazapine until or shortly before birth, your baby will be examined for possible side effects.

Consult your doctor if you can breastfeed while taking Mirtazapine Combix.

If you are taking Mirtazapine Combix during pregnancy, tell your midwife and/or doctor. When similar medicines (called selective serotonin reuptake inhibitors: SSRIs) are taken during pregnancy, there may be an increased risk that the baby will suffer from a serious disease called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and appear blue. These symptoms usually start during the first 24 hours after birth. If this happens in your case, you must 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 use tools or machines until you know how the treatment with Mirtazapine Combix affects you.

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

3. How to take Mirtazapine Combix

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

How much to take

The usual starting dose is 15 or 30 mg per day. Your doctor may recommend that you increase the 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 Combix at the same time every day.

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

Normally, Mirtazapine Combix will start to work after 1 or 2 weeks, and after 2 to 4 weeks, you may start to feel better. It is essential that during the first few weeks of treatment, you talk to your doctor about the effects of mirtazapine.

• between 2 and 4 weeks after starting to take 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 takes too much Mirtazapine Combix, contact a doctor immediately.

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

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

If you forget to take Mirtazapine Combix

If you have to take your dose once a day

If you have to take your dose twice a day

If you stop taking Mirtazapine Combix

• Stop taking mirtazapine only if you consult your doctor.

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

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

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

4. Possible Adverse Effects

Like all medicines, Mirtazapine Combix can cause adverse effects, although not all people suffer from them.

Some adverse effects are more likely to occur than others. The possible adverse effects of mirtazapine are indicated below and can be divided into:

• 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 less than 1 in 10,000 patients
• Unknown:cannot be estimated from the available information

Very Common:

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

Common:

• lethargy
• dizziness
• tremor
• nausea
• diarrhea
• vomiting
• 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 were resolved when treatment was discontinued.

Uncommon:

• feeling of exaggerated euphoria (mania).

• Stop taking mirtazapine and consult your doctor immediately.
• • strange sensation in the skin, such as burning, pricking, tingling, or numbness (paresthesia)
  • involuntary movements of the legs during sleep
  • fainting (syncope)
  • numbness in the mouth (oral hypoesthesia)
  • low blood pressure
  • nightmares
  • agitation
  • hallucinations
  • inability to remain still.

Rare:

• yellowing of the eyes or skin; may suggest liver function alterations (jaundice).

• Stop taking mirtazapine and consult your doctor immediately.
• • tics or muscle contractions (myoclonus).
  • Pancreatitis

Unknown:

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

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

In rare cases, mirtazapine may 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).

• Stop taking mirtazapine and consult your doctor immediately.
• • combination of symptoms such as unexplained fever, sweating, palpitations, diarrhea, muscle contractions (involuntary), chills, exaggerated reflexes, agitation, mood changes, and loss of consciousness. In very rare cases, these symptoms can be signs of a disorder called "serotonin syndrome".
• Stop taking mirtazapine and consult your doctor immediately.
• • thoughts of self-harm or suicide.
• Stop taking mirtazapine and consult your doctor immediately.
• • abnormal sensations in the mouth (oral paresthesia).
  • swelling in the mouth (oral edema).
  • hyponatremia.
  • inadequate secretion of antidiuretic hormone.
  • red patches on the trunk, such as circumscribed or circular macules, 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).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: 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 that appears on the packaging and on the blister, after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and

the medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt

ask your pharmacist how to dispose of the packaging and medicines you no longer

need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Mirtazapine Combix

• The active ingredient is mirtazapine.

Mirtazapine Combix 30 mg film-coated tablets contain 30 mg of mirtazapine per tablet.

• The other components are:

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

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

Appearance of the Product and Package Contents

Mirtazapine Combix are film-coated tablets.

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

The tablet can be divided into two equal halves.

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

The following package 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 Pätures

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 Last Revision of this Prospectus: September 2020

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