Zapin

Patient Information Leaflet: Information for the User

Zapin 30 mg film-coated tablets

Mirtazapine
Generic medicine
Please read all of this leaflet carefully before you start 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, ask your doctor, pharmacist or nurse.
• 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 may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Zapin is and what it is used for

Zapin contains the active substance mirtazapine and belongs to a group of medicines called antidepressants.
Zapin is used to treat depression disorders in adults.
It takes Zapin 1 to 2 weeks before it starts to work. After 2 - 4 weeks you will begin to feel better. You should contact your doctor if you do not feel better or if you feel worse after 2 - 4 weeks. Further information is included in section 3 under the heading "When to expect to feel better".

2. What you should know before taking Zapin

Do not take Zapin

• 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 inform your doctor as soon as possible before taking Zapin.
• If you are taking or have recently taken (within the last 2 weeks) medicines called monoamine oxidase inhibitors (MAO-Is).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Zapin.
DO NOT TAKE – OR – INFORM YOUR DOCTOR BEFORE TAKING ZAPIN:
If you have ever had a severe skin rash or skin peeling, blisters and/or mouth ulcers
after taking mirtazapine or other medicines.

Children and adolescents
Zapin should normally not be used in children and adolescents under 18 years of age, as efficacy has not been demonstrated. In addition, it is important to know that in patients under 18 years of age, this class of medicines is associated with an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (particularly aggression, hostile behavior, and rage) when taking this class of medicines. Nevertheless, your doctor may prescribe Zapin to patients under 18 years of age if they consider it to be in their best interest. If your doctor has prescribed Zapin to a patient under 18 years of age and you wish to discuss this further, please consult your doctor again. Inform your doctor if any of the symptoms described above appear or worsen in patients under 18 years of age who are taking Zapin. Furthermore, the long-term safety effects of Zapin on growth, maturation, and cognitive and behavioral development in this age group have not yet been established. In addition, a significant weight gain during treatment with Zapin has been observed more frequently in this age group compared to adults.

Suicidal thoughts and worsening of depression
If you are depressed, you may sometimes think about harming yourself or committing suicide. These thoughts may increase shortly after starting treatment with antidepressants, as all 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 suicide or self-harm.
• You are a young adult. Clinical study data have shown an increased risk of suicidal behavior in adults under 25 years of age with psychiatric disorders being treated with antidepressants.

If at any time you find yourself thinking about suicide or self-harm, contact your doctor or go to the hospital immediately.
It may be helpful to tell a relative or friend that you are suffering from depression and ask them to read this leaflet. You may ask them to inform you if they think your depression is worsening or if they are concerned about changes in your behavior.

Be especially careful with Zapin

• If you suffer or have ever suffered from any of the following conditions. Inform your doctor about these conditions before taking Zapin, if you have not already done so:
• Seizures (epilepsy). If you begin to have seizures or if seizures become more frequent, stop taking Zapin and contact your doctor immediately;
• Liver disease, including jaundice. If jaundice occurs, stop taking Zapin 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 (periods of euphoria/hyperactivity alternating with periods of depression). If you start feeling elated or overexcited, stop taking Zapin and contact your doctor immediately;
• Diabetes (your insulin dose or other antidiabetic medicines may need to be adjusted);
• Eye disease, such as increased eye pressure (glaucoma);
• Difficulty passing urine, which may be caused by an enlarged prostate;
• Certain types of heart disease that may affect your heart rhythm, recent heart attack, heart failure, or if you are taking certain medicines that may affect your heart rhythm.
• If you develop signs of infection, such as unexplained high fever, sore throat, and mouth ulcers.

Stop taking Zapin 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 side effects of antidepressants.

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 consult a doctor immediately if you notice any of the symptoms described in section 4 related to these serious adverse reactions.
If you have previously experienced severe skin reactions, treatment with Zapin should not be restarted.

Other medicines and Zapin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Zapin in combination with:

• Monoamine oxidase inhibitors (MAO inhibitors). In addition, do not take Zapin within two weeks after stopping treatment with MAO inhibitors. If you stop taking Zapin, do not take MAO inhibitors during the following two weeks. MAO inhibitors include, for example, moclobemide, tranylcypromine (both are antidepressants), and selegiline (used in Parkinson’s disease).

Be cautious when taking Zapin together 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), St. John’s wort – Hypericum perforatum (a herbal remedy used to treat depression). In very rare cases, Zapin alone or in combination with these medicines may cause a condition known as serotonin syndrome. Some symptoms of this syndrome include unexplained fever, sweating, increased heart rate, diarrhea, muscle twitching (involuntary), tremor, hyperactive reflexes, restlessness, mood changes, and loss of consciousness. If you experience a combination of these symptoms, contact your doctor immediately.
• The antidepressant nefazodone. This may increase the amount of Zapin in your blood. Inform your doctor if you are taking this medicine. It may be necessary to reduce the dose of Zapin, or when nefazodone is discontinued, to increase the dose of Zapin again.
• Medicines for anxiety or insomnia, such as benzodiazepines; medicines for schizophrenia, such as olanzapine; medicines for allergies, such as cetirizine; strong pain medicines, such as morphine. Zapin, when taken together with these medicines, may increase the drowsiness already caused by these medicines.
• Medicines to treat infections, such as antibacterial medicines (e.g., erythromycin), antifungal medicines (e.g., ketoconazole), HIV/AIDS medicines (e.g., HIV protease inhibitors), and medicines for stomach ulcers (e.g., cimetidine). These medicines, when combined with Zapin, may increase the amount of Zapin in your blood. Inform your doctor if you are taking these medicines. It may be necessary to reduce the dose of Zapin, or when these medicines are discontinued, to increase the dose of Zapin again.
• Medicines for epilepsy, such as carbamazepine and phenytoin.
• Medicines for tuberculosis, such as rifampicin. These medicines, when combined with Zapin, may decrease the amount of Zapin in your blood. Inform your doctor if you are taking these medicines. It may be necessary to increase the dose of Zapin, or when these medicines are discontinued, to reduce the dose of Zapin again.
• Medicines that prevent blood clotting, such as warfarin. Zapin 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 closely monitor your blood.
• Medicines that may affect heart rhythm, such as certain antibiotics and certain antipsychotics.

Zapin with food and alcohol
You may experience drowsiness if you consume alcoholic beverages while taking Zapin.
It is recommended not to consume alcoholic beverages.
You may take Zapin 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.

Pregnancy:
Limited experience with the administration of Zapin to pregnant women does not indicate an increased risk. However, caution is advised if used during pregnancy.
If you take Zapin up to or immediately before delivery, the newborn must be closely monitored for possible adverse effects.
Ensure that your midwife and/or doctor know that you are taking Zapin. Similar medicines (SSRIs), when taken during pregnancy, may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes 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.

Breastfeeding:
Ask your doctor whether you can breastfeed while taking Zapin.

Driving and using machines
Zapin may affect your concentration or attention. Make sure these abilities are not impaired before driving or operating machinery. If your doctor has prescribed Zapin to a patient under 18 years of age, ensure that concentration and attention are not impaired before driving in traffic (e.g., cycling).

Zapin contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

Zapin contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e., essentially ‘sodium-free’.

3. How to take Zapin

Take this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended starting dose is 15 or 30 mg daily. Your doctor may advise you to increase the dose
after a few days until reaching the amount most suitable for you (between 15 and 45 mg daily).
Normally the dose is the same for all ages. However, if you are elderly or suffer from kidney or liver
diseases, your doctor may adjust the dose.
When to take Zapin
Take Zapin at the same time every day. It is best to take Zapin as a single dose before going to
bed. However, your doctor may suggest splitting the dose, taking one in the morning and one in the
evening before going to bed. The higher dose should be taken before going to bed. Take the
tablets orally. Swallow the prescribed dose of Zapin without chewing, with a little water or
fruit juice.
Film-coated 30 mg tablets
The tablet may be divided into equal doses.
When you can expect to start feeling better
Zapin usually takes 1–2 weeks to start working, and after 2–4 weeks you may start to feel
better.
It is important that during the first weeks of treatment you discuss the effects of Zapin with your doctor:
→ 2 to 4 weeks after starting Zapin, talk to your doctor about how this medicine has affected you.
If you continue not to feel better, your doctor may prescribe a higher dose. In this case, talk to your
doctor again after another 2–4 weeks.
Usually, you will need to continue taking Zapin for 4–6 months after the symptoms of depression have
disappeared.
If you take more Zapin than you should
If you or someone else has taken too much Zapin, contact your doctor immediately.
The most likely signs of an overdose of Zapin (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 Zapin
If you are supposed to take the dose once a day:

• Do not take a double dose to make up for the missed dose. Take the next dose at the usual time.
  If you are supposed to take the dose twice a day:
• If you forgot to take the morning dose, simply take it together with the evening dose.
• If you forgot to take the evening dose, do not take it together with the next morning dose; just skip it and continue normally with the morning and evening doses.
• If you forgot to take both doses, do not try to make up for the missed doses. Skip both doses and continue the next day with your regular morning and evening doses.
  If you stop taking Zapin
  Stop taking Zapin only after consulting your doctor.
  If you stop too early, depression may return. When you start feeling better, discuss this with your
  doctor. Your doctor will decide when to stop treatment.
  Do not stop taking Zapin abruptly, even when depression has improved. If you stop taking Zapin
  abruptly, you may feel unwell, experience dizziness, agitation or anxiety, and have headaches. These
  symptoms can be avoided by gradually stopping the medicine.
  Your doctor will advise you on how to gradually reduce the dose.
  If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following serious side effects, stop taking Zapin
and contact your doctor immediately.

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

• Feeling euphoric or emotionally "high" (mania).

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

• Yellowing of the skin or eyes; this may indicate liver dysfunction (jaundice).

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

• Signs of infection such as sudden unexplained fever, sore throat, and mouth ulcers (agranulocytosis). In rare cases, mirtazapine may cause disturbances in blood cell production (bone marrow depression). Some people may become more susceptible to infections because mirtazapine may 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).
• Seizure (convulsions).
• A combination of symptoms such as unexplained fever, sweating, increased heart rate, diarrhoea, uncontrollable muscle contractions, chills, hyperactive reflexes, restlessness, mood changes, loss of consciousness, and increased salivation. In very rare cases, these may be signs of serotonin syndrome.
• Thoughts of harming yourself or of suicide.
• Red spots on the trunk, target-shaped or circular, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Widespread rash, elevated body temperature, 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 weight gain
• Drowsiness or sedation
• Headache
• Dry mouth

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

• Lethargy
• Dizziness
• Tremors or jerks
• 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 (typically in the ankles or feet) due to fluid retention (oedema)
• Fatigue
• Vivid dreams
• Confusion
• Feeling anxious
• Sleep disturbances
• Memory problems, which in most cases resolve after discontinuation of treatment

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

• Abnormal skin sensations, e.g., burning, pricking, tingling, or pins and needles (paraesthesia)
• Restless legs
• Fainting (syncope)
• Numbness of the mouth (oral hypoesthesia)
• Low blood pressure
• Nightmares
• Feeling of restlessness
• Hallucinations
• Urge to move

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

• Muscle contractions or spasms (myoclonus)
• Aggression
• Abdominal pain and nausea; this may suggest inflammation of the pancreas (pancreatitis)

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

• Abnormal sensations in the mouth (oral paraesthesia)
• Swelling in the mouth (mouth oedema)
• Swelling throughout the body (generalised oedema)
• Localised swelling
• Low sodium levels in the blood which may cause headache, fatigue, seizures, and coma (hyponatraemia)
• Inappropriate secretion of antidiuretic hormone
• Severe skin reactions (bullous dermatitis, erythema multiforme)
• Sleepwalking (somnambulism)
• Speech disorders
• 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 (hyperprolactinaemia, including symptoms such as breast enlargement and/or milk discharge from nipples)
• Painful and prolonged penile erection

Additional side effects in children and adolescents
In clinical studies, the following side effects were commonly observed in children under 18 years of age: 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 can also report side effects directly via the national reporting system at 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 Zapin

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
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 that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Zapin contains

• The active substance is mirtazapine.

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

• The other components are:
  Tablet core: monohydrate lactose, pregelatinized corn starch, anhydrous colloidal silicon dioxide (E551), sodium croscarmellose (E468), magnesium stearate (E470b).
  Tablet coating: hypromellose (E464), macrogol 8000 (E1521), titanium dioxide (E171), talc. The film coating of Zapin 30 mg film-coated tablets also contains yellow iron oxide (E172) and red iron oxide (E172).

Description of the appearance of Zapin and package contents
Zapin is film-coated tablets.
Brownish tablets, with a score line on both sides, oval, biconvex, film-coated,
12.7 x 6.5 mm in diameter. Marked with "I" on one side. The tablet can be divided into two equal parts.
Packaging
30 tablets in blister packs.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Ecupharma S.r.l.
Via Mazzini 20
20123 Milan
Italy
Manufacturer
Actavis Ltd.
BLB 015, BLB 016 Bulebel Industrial Estate,
Zejtun ZTN 3000
Malta

This medicinal product is authorized in the European Economic Area member states
under the following names:
Italy: Zapin