Apotiapina

Package leaflet: Information for the patient

ApoTiapina, 25 mg, coated tablet
ApoTiapina, 100 mg, coated tablet
ApoTiapina, 200 mg, coated tablet
Quetiapinum
Please read the entire leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• Consult your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are similar.
• If any side effects worsen or if you experience any side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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

1. What ApoTiapina is and what it is used for

ApoTiapina contains a substance called quetiapine, which belongs to a group of medicines known as antipsychotics. ApoTiapina may be used in the treatment of conditions such as:

• Depressive episodes in bipolar disorder: when the patient feels deep sadness, experiences low mood, guilt, lack of energy and appetite, or has difficulty falling asleep.
• Mania: the patient may be highly excited, elated, overactive, overly enthusiastic, or excessively active; may also have impaired judgment, including aggressive or destructive behaviors.
• Schizophrenia: the patient may hear or sense things that are not real, have beliefs that are not based in reality, or be extremely suspicious, fearful, disoriented, feel guilt, or experience tension or low mood.

Your doctor may advise you to continue taking ApoTiapina even after you start feeling better.

2. Important information before using ApoTiapina

When not to use ApoTiapina:

• If the patient is allergic to quetiapine or any of the other ingredients of this medicine (listed in section 6).
• If the patient is taking any of the following medicines: certain medicines used in HIV infection, azole derivatives (used in fungal infections), erythromycin or clarithromycin (used in bacterial infections), or nefazodone (used in depression).
  If the patient is unsure, they should consult their doctor or pharmacist before taking this medicine.

Warnings and precautions
Before starting treatment with ApoTiapina, discuss with your doctor or pharmacist if:

• the patient or someone in their family has or has had any heart problems, such as heart rhythm disorders, weakened heart muscle, or myocarditis, or if the patient is taking or has taken any medicines that may affect heart function
• the patient has low blood pressure
• the patient has had a stroke, particularly if they are elderly
• the patient has liver problems
• the patient has ever had a seizure (epilepsy)
• the patient has diabetes or is at risk of developing diabetes. In such cases, the doctor may monitor the patient's blood sugar levels during treatment with ApoTiapina
• the patient has previously had a reduced number of white blood cells (which may or may not have been caused by other medicines)
• the patient is elderly and has dementia (impaired brain function). ApoTiapina should not be used in these patients, as medicines in the class to which it belongs may increase the risk of stroke and, in some cases, risk of death in elderly patients with dementia
• the patient is elderly and has Parkinson’s disease/parkinsonism
• the patient or someone in their family has had a blood clotting disorder, because medicines in the class to which ApoTiapina belongs may increase the risk of blood clots
• the patient has or has had brief episodes of breathing cessation during normal nighttime sleep (called "sleep apnoea") and is taking medicines that slow down normal brain function ("depressants")
• the patient has or has had a condition where they cannot completely empty their bladder (urinary retention), enlarged prostate, intestinal obstruction, or increased intraocular pressure. These conditions may sometimes be caused by medicines (called "anticholinergic medicines") that affect nerve cell function, used to treat certain conditions
• the patient has a history of alcohol or drug abuse
• the patient has depression or other conditions treated with antidepressants. Taking these medicines together with ApoTiapina may lead to serotonin syndrome, a potentially life-threatening condition (see "ApoTiapina with other medicines").

Immediately inform the doctor if any of the following symptoms occur after taking ApoTiapina:

• fever, severe muscle stiffness, excessive sweating, or altered consciousness (so-called "neuroleptic malignant syndrome"). Immediate medical help may be required.
• involuntary muscle movements, mainly of the face and tongue
• dizziness or extreme drowsiness; these changes in elderly patients may increase the risk of accidental injury (falls)
• seizures (epilepsy)
• prolonged painful erection (priapism)
• rapid or irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or unexplained fatigue. The doctor will need to examine the heart and, if necessary, refer the patient immediately to a cardiologist.

Such effects may occur during treatment with this type of medicine.
Promptly inform the doctor if the patient experiences:

• fever, flu-like symptoms, sore throat, or any infection as a result of very low white blood cell count. Discontinuation of ApoTiapina and/or appropriate treatment may be necessary.
• constipation accompanied by persistent abdominal pain or constipation that does not resolve with treatment, which may lead to severe intestinal obstruction.
• Suicidal thoughts and worsening depression
  If the patient has depression, they may sometimes experience thoughts of self-harm or suicide. These thoughts may particularly intensify at the beginning of treatment, as all medicines in this class take time to become effective—usually about 2 weeks, although sometimes longer. The risk of such thoughts is also higher if the patient suddenly stops taking the medicine. Additionally, this risk is greater in young adults. Clinical trial data have shown an increased risk of suicidal thoughts and/or behaviours in young adults under 25 years of age with depression.

If the patient experiences thoughts of self-harm or suicide, they should contact their doctor immediately or go to the nearest hospital. It may be helpful to inform family members or friends about the depression and ask them to read this leaflet. The patient may also ask these individuals to inform them if they notice worsening depression symptoms or other concerning behavioural changes.

Severe cutaneous adverse reactions (SCAR)
Very rarely, severe skin adverse reactions (SCAR), which may be life-threatening or fatal, have been reported during treatment with this medicine. Symptoms of these reactions usually include:

• Stevens-Johnson syndrome (SJS): widespread blistering rash and peeling skin, especially around the mouth, nose, eyes, and genitals
• Toxic epidermal necrolysis (TEN): a more severe form of rash causing extensive skin peeling
• Drug reaction with eosinophilia and systemic symptoms (DRESS): flu-like symptoms with rash, fever, swollen glands, and abnormal blood test results (including increased white blood cells (eosinophilia) and increased liver enzyme activity)
• Acute generalised exanthematous pustulosis (AGEP): small pustules filled with pus
• Erythema multiforme (EM): skin rash with irregular, itchy, red patches.

If the patient develops any of these symptoms, ApoTiapina should be discontinued immediately and the patient should contact their doctor or seek medical help without delay.

Weight gain
Weight gain has been reported in patients taking ApoTiapina. The patient, together with their doctor, should regularly monitor body weight.

Children and adolescents
Children and adolescents under 18 years of age should not take ApoTiapina.

ApoTiapina with other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

Do not take ApoTiapina if the patient is taking any of the following medicines:

• Certain medicines used in HIV infection.
• Azole derivatives (used in fungal infections).
• Erythromycin or clarithromycin (used in bacterial infections).
• Nefazodone (used in depression).

Tell the doctor if the patient is taking any of the following medicines:

• Antiepileptic medicines (such as phenytoin or carbamazepine).
• Medicines used for high blood pressure.
• Barbiturates (used for insomnia).
• Thioridazine or lithium (another antipsychotic medicine).
• Medicines affecting heart rhythm, e.g. medicines that may cause electrolyte imbalances (low potassium or magnesium levels), such as diuretics (water tablets) or certain antibiotics (used to treat infections).
• Medicines that may cause constipation.
• Medicines (called "anticholinergic medicines") that affect nerve cell function, used to treat certain medical conditions.
• Antidepressants. These medicines may interact with ApoTiapina and cause symptoms such as involuntary rhythmic muscle contractions, including eye movement muscles, agitation, hallucinations, coma, excessive sweating, tremor, increased reflexes, increased muscle rigidity, and body temperature above 38°C (serotonin syndrome). If such symptoms occur, contact the doctor immediately.

Before stopping any medicine, the patient should consult their doctor.

ApoTiapina, food, drink, and alcohol

• ApoTiapina may be taken with or without food.
• During treatment with ApoTiapina, alcohol consumption should be limited, as it may increase drowsiness.
• Do not drink grapefruit juice during treatment with ApoTiapina. Grapefruit juice may affect the medicine’s action.

Pregnancy and breastfeeding
During pregnancy, while breastfeeding, if pregnancy is suspected, or if planning a pregnancy, consult a doctor or pharmacist before using ApoTiapina. Do not use ApoTiapina during pregnancy without consulting the doctor. ApoTiapina should not be taken during breastfeeding.

The following symptoms may occur in newborns whose mothers took quetiapine during the third trimester of pregnancy (last three months): tremor, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If any of these symptoms occur in the newborn, medical advice should be sought.

Driving and operating machinery
ApoTiapina may cause drowsiness. The patient should not drive or operate machinery until they know how this medicine affects them.

Effect on urine drug screening tests
In patients taking ApoTiapina, urine drug screening tests performed by certain methods may show false-positive results for methadone or tricyclic antidepressants, even if the patient has not taken these drugs. In such cases, more specific testing is recommended.

Excipients:

ApoTiapina contains lactose monohydrate
This medicine contains lactose monohydrate, a type of sugar. If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

ApoTiapina contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning the medicine is considered "sodium-free".

Tartrazine (E110)
One of the ingredients of ApoTiapina 25 mg is tartrazine (E110), which may cause allergic reactions.

3. How to use ApoTiapina

This medicine should always be taken exactly as directed by the doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Your doctor will determine the initial dose. The maintenance dose (daily dose) depends on the type
of illness and individual patient needs, but usually ranges from 150 mg to 800 mg.

• Tablets should be taken once daily before bedtime or twice daily, depending on the patient's condition.
• Tablets should be swallowed whole with water.
• Tablets may be taken with food or independently of meals.
• Grapefruit juice should not be consumed during treatment with this medicine, as it may interfere with its action.
• Do not discontinue treatment without consulting your doctor, even if the patient feels better.

Patients with impaired liver function
In patients with liver problems, the doctor may adjust the dose.
Elderly patients
In elderly patients, the doctor may adjust the dose.
Use in children and adolescents under 18 years of age
ApoTiapina must not be used in children and adolescents under 18 years of age.
Taking more ApoTiapina than recommended
If a patient takes more than the recommended dose, symptoms such as drowsiness, dizziness, and
irregular heartbeat may occur. Seek immediate medical advice from a doctor or go to the nearest
hospital. Bring the ApoTiapina tablets with you.
Missed dose of ApoTiapina
If a patient forgets to take a dose, it should be taken as soon as remembered. However, if it is almost
time for the next dose, the missed dose should be skipped. Do not take a double dose to make up for
the missed dose.
Stopping ApoTiapina treatment
If ApoTiapina treatment is stopped abruptly, difficulty sleeping (insomnia), nausea, headache,
diarrhea, vomiting, dizziness, and irritability may occur. Before stopping treatment, the doctor may
recommend gradually reducing the dose.
If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
If any of the adverse effects worsen or if any adverse effects not listed in this leaflet occur,
you should inform your doctor or pharmacist.

Very common: may affect more than 1 in 10 people

• Dizziness (may lead to falls), headache, dryness of the oral mucosa.
• Drowsiness (may diminish during treatment with ApoTiapina) (may lead to falls).
• Withdrawal symptoms (symptoms occurring after discontinuation of ApoTiapina): difficulty falling asleep (insomnia), nausea, headache, diarrhoea, vomiting, dizziness, and irritability. Gradual discontinuation of the medicine over at least 1 to 2 weeks is recommended.
• Weight gain.
• Abnormal muscle contractions. These include difficulty initiating muscle movement, tremors, muscle restlessness, or muscle stiffness without concomitant pain.
• Changes in blood levels of certain lipids: increased triglyceride levels, total cholesterol (mainly LDL cholesterol), decreased HDL cholesterol.
• Decreased haemoglobin concentration in blood.

Common: may affect up to 1 in 10 people

• Increased heart rate.
• Palpitations, rapid heartbeat, irregular heartbeat.
• Constipation, stomach irritation (dyspepsia).
• Weakness.
• Swelling of hands or feet.
• Decreased blood pressure upon standing, which may cause dizziness or fainting (may lead to falls).
• Increased blood glucose levels.
• Blurred vision.
• Sleep disturbances and nightmares.
• Increased appetite.
• Irritability.
• Speech and thought disturbances.
• Suicidal thoughts and worsening of depression.
• Shortness of breath.
• Vomiting (mainly in elderly people).
• Fever.
• Changes in thyroid hormone levels in blood.
• Decreased blood count of certain types of blood cells.
• Increased liver enzyme activity in blood (ALT, gamma-GT).
• Increased blood levels of a hormone called prolactin. This may cause:
• breast enlargement in both men and women, and unexpected milk leakage from the nipples
• absence or irregular menstruation in women.

Uncommon: may affect up to 1 in 100 people

• Seizures or convulsive fits.
• Allergic reactions including blisters (vesicles), skin swelling, and swelling around the mouth.
• Unpleasant sensations in the legs (restless legs syndrome).
• Difficulty swallowing.
• Involuntary muscle movements, mainly of the face and tongue.
• Sexual dysfunction.
• Diabetes.
• Changes in the heart's electrical activity visible on ECG (prolongation of the QT interval).
• Slower than normal heart rate, which may occur at the beginning of treatment and may be associated with low blood pressure and fainting.
• Difficulty urinating.
• Fainting (may lead to falls).
• Nasal congestion.
• Decreased number of red blood cells, platelets, and certain types of white blood cells.
• Decreased thyroid hormone levels in blood, hypothyroidism.
• Increased liver enzyme activity in blood (AST).
• Decreased sodium concentration in blood.
• Worsening of pre-existing diabetes.
• Disorientation.

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

• Concurrent occurrence of high body temperature (fever), sweating, muscle stiffness, severe drowsiness or fainting (a condition known as "neuroleptic malignant syndrome").
• Yellowing of the skin and eyes (jaundice).
• Hepatitis.
• Prolonged and painful erection (priapism).
• Breast swelling and unexpected milk secretion (galactorrhoea).
• Menstrual cycle disturbances.
• Formation of blood clots in veins, particularly in the legs (symptoms include swelling, pain, and redness in the legs); a fragment of the clot may travel through the bloodstream to the lungs, causing chest pain and breathing difficulties; if any of these symptoms occur, the patient should seek immediate medical attention from a doctor or hospital.
• Walking, talking, eating, or performing other activities during sleep.
• Decreased body temperature (hypothermia).
• Pancreatitis.
• A condition (referred to as "metabolic syndrome") in which 3 or more of the following symptoms occur simultaneously: increased abdominal fat, decreased "good cholesterol" (HDL-C), increased levels of certain blood lipids (triglycerides), high blood pressure, and increased blood glucose levels.
• Concurrent occurrence of fever, flu-like symptoms, sore throat, or presence of any other infection with a very low white blood cell count (a condition known as agranulocytosis).
• Intestinal obstruction.
• Increased blood levels of creatine kinase (a substance derived from muscles).

Very rare: may affect up to 1 in 10,000 people

• Severe rash, blisters, or red spots on the skin.
• Severe hypersensitivity reactions (anaphylactic reactions) manifesting as breathing difficulties or shock.
• Rapid swelling of the skin, usually around the eyes, mouth, and throat (angioedema).
• Severe disorder with blister formation on the skin, mouth, eyes, and genital organs (Stevens-Johnson syndrome), see section 2.
• Inappropriate secretion of a hormone regulating urine volume.
• Muscle fiber breakdown and muscle pain (rhabdomyolysis).

Frequency not known: cannot be estimated from available data

• Skin rash with irregular red patches (erythema multiforme), see section 2.
• Sudden appearance on the skin of red areas with small blisters (small blisters filled with whitish-yellow fluid, known as acute generalized exanthematous pustulosis (AGEP), see section 2.
• Severe, sudden allergic reaction with symptoms such as fever, blister formation on the skin, and skin peeling (toxic epidermal necrolysis), see section 2.
• Rash with eosinophilia and systemic symptoms (DRESS), including flu-like symptoms with rash, fever, swollen lymph nodes, and abnormal blood test results including increased white blood cells (eosinophilia) and liver enzyme activity. See section 2.
• Withdrawal symptoms may occur in newborns of mothers who took ApoTiapina during pregnancy.
• Stroke.
• Heart muscle disorders (cardiomyopathy).
• Inflammation of the heart muscle (myocarditis).
• Blood vessel inflammation (vasculitis), often with skin rash presenting as small red or purple nodules.

Medicines from the same group as ApoTiapina may cause heart rhythm disturbances, which
can be dangerous and, in severe cases, may lead to death.
Some adverse effects can only be detected through laboratory blood tests. These include
changes in blood levels of certain lipids (triglycerides and total cholesterol) or glucose,
changes in thyroid hormone levels in blood, increased liver enzyme activity in blood,
decreased number of certain types of blood cells, decreased number of red blood cells,
increased blood levels of creatine kinase (a substance derived from muscles), decreased
sodium concentration in blood, and increased blood levels of a hormone—prolactin.
Elevated levels of this hormone may lead to:

• breast swelling in both men and women, and unexpected milk leakage from the nipples,
• absence or irregular menstruation in women.

Your doctor may recommend periodic monitoring tests.

Additional adverse effects in children and adolescents
Children and adolescents may experience the same adverse effects as adults.
The following adverse effects have been observed more frequently or exclusively in children and adolescents:

Very common: may affect more than 1 in 10 people

• Increased blood levels of a hormone called prolactin. Elevated prolactin levels may rarely cause: in boys and girls—breast enlargement and milk leakage from the nipples; in girls—absence of menstruation or irregular menstrual cycles.
• Increased appetite.
• Vomiting.
• Abnormal muscle contractions, including difficulty initiating intended movements, tremors, restlessness, or muscle stiffness without concomitant pain.
• Increased blood pressure.

Common: may affect up to 1 in 10 people

• Feeling of weakness, fainting (may lead to falls).
• Nasal congestion.
• Feeling of irritability.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, you should inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl .
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to gather more information on the safety of this medicine.

5. How to store ApoTiapina

Keep in the original packaging.
The medicine should be stored in a place that is out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What ApoTiapina contains
The active substance is quetiapine.
Each 25 mg coated tablet contains 25 mg of quetiapine (as quetiapine fumarate).
Each 100 mg coated tablet contains 100 mg of quetiapine (as quetiapine fumarate).
Each 200 mg coated tablet contains 200 mg of quetiapine (as quetiapine fumarate).

The other ingredients are:
Tablet core: hypromellose 2910 (E464), calcium hydrogen phosphate dihydrate, lactose monohydrate, corn starch, sodium carboxymethyl starch (type A), magnesium stearate, microcrystalline cellulose PH 102, talc, colloidal anhydrous silica.

Tablet coating:
25 mg: iron oxide red and yellow (E172), hypromellose 2910 (E464), titanium dioxide (E171), macrogol 400, sunset yellow (E110).
100 mg: iron oxide yellow (E172), hypromellose 2910, titanium dioxide (E171), macrogol 400.
200 mg: hydroxypropylcellulose (E463), hypromellose 2910 (E464), talc, titanium dioxide (E171).

What ApoTiapina looks like and contents of the pack
25 mg: peach-coloured, round, biconvex coated tablets, approximately 5.7 mm in diameter.
100 mg: yellow, round, biconvex coated tablets with a score line on one side, approximately 9.1 mm in diameter.
200 mg: white, round, biconvex coated tablets with a score line on one side, approximately 12.1 mm in diameter.

The 100 mg and 200 mg coated tablets can be divided into equal doses.

Pack sizes:
The packaging contains:
25 mg: 30 coated tablets (in blisters of 10 tablets).
100 mg, 200 mg: 30 or 60 coated tablets (in blisters of 10 tablets).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Aurovitas Pharma Polska Sp. z o.o.
Sokratesa 13D lok. 27
01-909 Warsaw
Poland

Manufacturer
Genepharm S.A.
18th km Marathonos Avenue
15351 Pallini Attikis,
Greece