Ketrel xr

Patient Information Leaflet

KETREL XR, 50 mg, prolonged-release tablets
KETREL XR, 200 mg, prolonged-release tablets
KETREL XR, 300 mg, prolonged-release tablets
KETREL XR, 400 mg, prolonged-release tablets
Quetiapinum
Please read the entire leaflet before taking this medicine, as it contains important information
for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents:

1. What KETREL XR, prolonged-release tablets are and what they are used for
2. Important information before taking KETREL XR, prolonged-release tablets
3. How to take KETREL XR, prolonged-release tablets
4. Possible side effects
5. How to store KETREL XR, prolonged-release tablets
6. Contents of the pack and other information

1. What KETREL XR, prolonged-release tablets are and what they are used for
The active substance in KETREL XR, prolonged-release tablets is quetiapine.
Quetiapine belongs to a group of medicines called antipsychotics. KETREL XR, prolonged-release
tablets may be used to treat the following conditions:

• Schizophrenia: when the patient hears or feels things that do not exist; believes in things that are not true; or shows unusual suspicion, anxiety, disorientation, feelings of guilt, tension, and depression.
• Mania: when the patient is highly excited, agitated, over-enthusiastic, excessively active, or has impaired critical judgment, including aggressive or destructive behaviors.
• Bipolar disorder and severe depressive episodes in major depressive disorder, when the patient experiences profound sadness or despair, feelings of guilt, lack of energy and appetite, or difficulty falling asleep.

In the treatment of severe depressive episodes in major depressive disorder, KETREL XR,
prolonged-release tablets will be used in combination with other medicines. Your doctor may decide
to continue treatment with KETREL XR even if you feel your condition has improved.

2. Important information before taking KETREL XR, prolonged-release tablets

Do not take KETREL XR, prolonged-release tablets if:

• You are allergic to quetiapine or any of the other ingredients of this medicine (listed in section 6).
• You are taking any of the following medicines:
  • certain medicines used to treat HIV infection,
  • azole antifungals (used in fungal infections),
  • erythromycin or clarithromycin (used in infections),
  • nefazodone (used to treat depression).

If any of the above situations apply to you, do not take KETREL XR, prolonged-release tablets.
Consult your doctor or pharmacist before taking KETREL XR, prolonged-release tablets.

Warnings and precautions
Before starting treatment with KETREL XR, prolonged-release tablets, discuss the following with your doctor:

• if you or a family member has a heart condition, such as heart rhythm disorders, heart weakness, or myocarditis (inflammation of the heart muscle), or if you are taking medicines that may affect heart rhythm,
• if you have low blood pressure,
• if you have had a stroke, especially if you are elderly,
• if you have liver problems,
• if you have ever had seizures (epilepsy),
• if you have diabetes or an increased risk of developing diabetes. If you are at risk, your doctor may order blood sugar tests while you are taking KETREL XR, prolonged-release tablets,
• if you have ever had a low white blood cell count (regardless of whether it was caused by other medicines),
• if you are an elderly person with dementia (reduced mental function). Such patients should not take KETREL XR, prolonged-release tablets, as medicines in this class may increase the risk of stroke and, in some cases, death in elderly patients with dementia,
• if you are an elderly person with Parkinson's disease/parkinsonism,
• if you or a family member has a history of venous thrombosis (blood clots), as use of medicines in this class has been associated with blood clot formation,
• if you have or have had a condition involving brief interruptions in breathing during normal sleep (sleep apnea) and are taking medicines that slow brain function,
• if you have or have had difficulty completely emptying the bladder (urinary retention), benign prostatic hyperplasia, intestinal obstruction, or increased intraocular pressure. These symptoms may sometimes be caused by medicines (so-called anticholinergics) used in treating certain conditions that affect nerve cell function,
• if you have or have had problems with alcohol or drug abuse.

Contact your doctor immediately if any of the following symptoms occur after taking KETREL XR, prolonged-release tablets:

• fever, muscle stiffness, excessive sweating, reduced level of consciousness (so-called neuroleptic malignant syndrome). Immediate medical help may be required,
• involuntary movements, especially of the face or tongue,
• dizziness or extreme drowsiness. This may increase the risk of accidental injury (falls) in elderly patients,
• seizures (fits),
• prolonged painful erection (priapism),
• rapid or irregular heartbeat, even at rest, palpitations, breathing difficulties, chest pain, or unexplained fatigue. Your doctor will need to examine your heart and, if necessary, refer you immediately to a cardiologist.

All these symptoms may occur during treatment with medicines in this therapeutic class.
Contact your doctor as soon as possible if you experience:

• fever, flu-like symptoms, sore throat, or other signs of infection, as these may be due to a very low white blood cell count, which may require discontinuation of KETREL XR and/or appropriate treatment;
• constipation with persistent abdominal pain or constipation that does not improve with treatment, as this may lead to severe intestinal obstruction.

Suicidal thoughts or worsening of depression.
Patients with depression may sometimes have thoughts about self-harm or suicide. These symptoms
or behaviors may worsen during the initial phase of treatment, as these medicines usually take about
2 weeks to start working, sometimes longer. Suicidal thoughts may increase in patients who suddenly
stop taking their medication. The likelihood of such thoughts is higher in younger patients. Clinical
trial data indicate an increased risk of suicidal thoughts and/or behaviors in young people under
25 years of age with depression.
If you ever have thoughts of self-harm or suicide, contact your doctor immediately or go to a
hospital. It may be helpful to inform friends and family about your depression and ask them to read
this leaflet. You may also ask them to inform you if they notice worsening of depressive symptoms
or other worrying changes in your behavior.

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

• Stevens-Johnson syndrome (SJS): widespread rash with blisters 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 elevated liver enzyme activity).

If any of these symptoms occur, stop taking KETREL XR and contact your doctor immediately.

Weight gain
Weight gain has been observed in patients taking KETREL XR, prolonged-release tablets. You should
regularly monitor your body weight, either by yourself or with your doctor.

Children and adolescents
KETREL XR, prolonged-release tablets are not intended for use in children and adolescents under
18 years of age.

KETREL XR, prolonged-release tablets and other medicines
Tell your doctor about all medicines you are currently taking, have recently taken, or plan to take.
Do not take KETREL XR, prolonged-release tablets if you are taking any of the following medicines:

• certain medicines used to treat HIV,
• azole antifungals (used in fungal infections),
• erythromycin or clarithromycin (used in infections),
• nefazodone (used to treat depression).

Tell your doctor if you are taking any of the following medicines:

• medicines used to treat epilepsy (such as phenytoin or carbamazepine),
• medicines used to treat high blood pressure,
• barbiturates (medicines used for sleep disorders),
• thioridazine or lithium (medicines used to treat psychotic disorders),
• medicines that affect heart rhythm, such as those altering electrolyte balance (reducing potassium or magnesium levels), including diuretics (water tablets) or certain antibiotics (medicines used for infections),
• medicines that may cause constipation,
• medicines used to treat certain conditions that affect nerve cell function (so-called anticholinergics).

Do not stop taking other medicines without consulting your doctor.

KETREL XR, prolonged-release tablets, food, drink, and alcohol

• Food may affect the action of the medicine; therefore, KETREL XR, prolonged-release tablets should be taken at least one hour before a meal or immediately before bedtime.
• Be cautious with alcohol consumption. Taking KETREL XR, prolonged-release tablets with alcohol may cause drowsiness.
• Do not drink grapefruit juice while taking KETREL XR, prolonged-release tablets. Grapefruit juice may affect the action of the medicine.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child,
consult your doctor or pharmacist before taking this medicine.
Do not take KETREL XR, prolonged-release tablets during pregnancy unless advised by your
doctor.
Do not breastfeed while taking KETREL XR, prolonged-release tablets.
Newborns whose mothers took KETREL XR during the third trimester of pregnancy (last 3 months)
may experience withdrawal symptoms such as tremors, muscle stiffness and/or weakness, drowsiness,
irritability, breathing difficulties, and feeding problems. If you notice any of these symptoms in your
baby, contact your doctor.

Driving and operating machinery
KETREL XR, prolonged-release tablets may cause drowsiness. You should not drive or operate
machinery until you know how you react to this medicine.

KETREL XR contains lactose.
KETREL XR, prolonged-release tablets contain lactose, a type of sugar. If you have been previously
diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

KETREL XR contains sodium
KETREL XR, prolonged-release tablets contain less than 1 mmol (23 mg) of sodium per tablet,
meaning these products are considered "sodium-free".

Urine drug screening tests
Taking KETREL XR may result in a positive test for methadone and certain antidepressants, so-called tricyclic antidepressants (TCA), even if you are not taking them. In such cases, more specific testing should be performed.

3. How to take KETREL XR, prolonged-release tablets

This medicine should always be taken as instructed by the doctor.
If in doubt, consult your doctor or pharmacist.
The starting dose will be determined by the doctor.
The maintenance (daily) dose depends on the condition and individual needs of the patient, and is usually between 150 mg and 800 mg.

• Take the medicine once daily.
• Do not divide, chew or crush the tablets.
• Swallow the tablets whole with water.
• Take the tablets on an empty stomach (at least one hour before a meal or just before bedtime, as directed by your doctor).
• Do not consume grapefruit juice during treatment with KETREL XR prolonged-release tablets, as it may affect the way the medicine works.
• Do not stop taking this medicine without consulting your doctor, even if you feel better.

Liver function disorders
Your doctor may adjust the dose of this medicine if you have impaired liver function.
Elderly patients
Your doctor may adjust the dose of this medicine in elderly patients.
Use in children and adolescents
KETREL XR prolonged-release tablets must not be used in children and adolescents under 18 years of age.
Taking more KETREL XR prolonged-release tablets than recommended
If more KETREL XR prolonged-release tablets are taken than recommended, the patient may experience drowsiness, dizziness, or irregular heartbeat. Seek immediate medical advice from a doctor or go to the nearest hospital. Take the medicine pack with you.
Missed dose of KETREL XR prolonged-release tablets
If a dose of KETREL XR prolonged-release tablets is missed, take it as soon as possible. However, if it is almost time for the next dose, wait and take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Stopping KETREL XR prolonged-release tablets
If KETREL XR prolonged-release tablets are stopped suddenly, difficulty sleeping (insomnia), nausea, headache, diarrhoea, vomiting, dizziness or irritability may occur. Your doctor may recommend gradually reducing the dose before stopping treatment completely.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.

Very common (may affect more than 1 in 10 people):

• dizziness (which may lead to falls), headache and dry mouth;
• somnolence (this symptom may diminish after some time on KETREL XR treatment) (may lead to falls);
• withdrawal symptoms (symptoms occurring after discontinuation of KETREL XR, prolonged-release tablets): difficulty sleeping (insomnia), nausea, headache, diarrhoea, vomiting, dizziness and irritability; gradual discontinuation over a period of at least 1-2 weeks is recommended;
• weight gain;
• abnormal muscle movements, including difficulty initiating movement, tremors, feeling of restlessness or muscle stiffness without pain;
• changes in levels of certain lipids (triglycerides and total cholesterol).

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

• increased heart rate;
• palpitations or accelerated or irregular heartbeat;
• constipation, indigestion (dyspepsia);
• feeling of weakness;
• swelling of hands and feet;
• low blood pressure upon standing (orthostatic hypotension). This may cause dizziness and fainting, which may lead to falls;
• increased blood glucose levels;
• blurred vision;
• unusual dreams and nightmares;
• increased feeling of hunger;
• feeling of irritability;
• speech disorders and difficulty speaking;
• suicidal thoughts and worsening of depression;
• shortness of breath;
• vomiting (mainly in elderly people);
• fever;
• changes in blood levels of thyroid hormones;
• decreased number of certain types of blood cells;
• increased liver enzyme activity in blood;
• increased blood levels of prolactin; elevated prolactin levels may rarely lead to:
  • breast enlargement and unexpected milk production in both men and women;
  • cessation of menstruation or irregular periods in women.

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

• seizures;
• allergic reactions, which may include skin blistering, skin swelling and swelling around the mouth;
• unpleasant sensations in the lower limbs (also known as restless legs syndrome);
• difficulty swallowing;
• uncontrolled movements, mainly of the face or tongue;
• sexual dysfunction;
• diabetes;
• changes in the electrical activity of the heart seen on ECG (prolongation of 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 in urination;
• fainting (may lead to falls);
• nasal congestion;
• decreased number of red blood cells (anaemia);
• decreased blood sodium levels (hyponatraemia);
• worsening of pre-existing diabetes.

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

• a syndrome of symptoms: high temperature (fever), sweating, muscle stiffness, severe drowsiness or fainting (a condition known as "neuroleptic malignant syndrome");
• yellowing of the skin and eyes (jaundice);
• hepatitis (liver inflammation);
• prolonged and painful erection (priapism);
• breast enlargement and unexpected milk production (galactorrhoea);
• menstrual disorders;
• blood clots in veins, especially in the legs (symptoms include swelling, pain and redness of the leg), which may travel through blood vessels to the lungs, causing chest pain and breathing difficulties. If any of these symptoms occur, seek immediate medical help;
• walking, talking, eating or performing other activities while asleep;
• decreased body temperature (hypothermia);
• pancreatitis (inflammation of the pancreas);
• a condition called "metabolic syndrome", in which 3 or more of the following features occur: increased abdominal fat tissue, decreased levels of "good cholesterol" HDL, increased blood triglyceride levels, high blood pressure, and increased blood glucose levels;
• combination of fever, flu-like symptoms, sore throat or other infection with a very low white blood cell count (so-called agranulocytosis);
• intestinal obstruction;
• increased blood creatine kinase activity (an enzyme produced, among others, in muscles).

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

• severe rash, blisters or red spots on the skin;
• severe allergic reaction (called anaphylaxis), which may cause difficulty breathing or shock;
• sudden swelling of the skin, usually around the eyes, lips and throat (angioedema);
• severe disorder with blister formation on the skin, in the mouth, eyes and genital organs (Stevens-Johnson syndrome) (see section 2);
• inappropriate secretion of the hormone regulating urine volume (syndrome of inappropriate antidiuretic hormone secretion – SIADH);
• breakdown of muscle fibres and muscle pain (rhabdomyolysis).

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

• skin rash accompanied by irregular skin patches (erythema multiforme);
• severe, sudden allergic reaction with symptoms such as fever, skin blisters, skin peeling (toxic epidermal necrolysis) (see section 2);
• drug reaction with eosinophilia and systemic symptoms (DRESS), including symptoms such as flu-like symptoms with rash, fever, swollen lymph nodes and abnormal blood test results (including increased white blood cell count (eosinophilia) and increased liver enzyme activity). See section 2.
• withdrawal symptoms in newborns whose mothers took KETREL XR prolonged-release tablets during pregnancy;
• stroke;
• heart muscle disorders (cardiomyopathy);
• inflammation of the heart muscle (myocarditis);
• inflammation of blood vessels (vasculitis), often with a skin rash presenting as small red or purple nodules.

The group of medicines to which KETREL XR prolonged-release tablets belong may cause disturbances in heart rhythm, which may be severe and, in serious cases, may lead to death.

Some adverse reactions are only detectable in blood tests. These include: changes in levels of certain fats (triglycerides and total cholesterol) or blood glucose, changes in blood levels of thyroid hormones, increased liver enzyme activity, decreased number of certain types of blood cells, decreased number of red blood cells (erythrocytes), increased blood creatine kinase activity (an enzyme present in muscles), decreased blood sodium levels, and increased blood prolactin levels.

Increased blood prolactin levels may rarely lead to:

• breast enlargement and unexpected milk production in both women and men;
• cessation or irregularity of menstruation in women.

Your doctor may recommend periodic blood tests.

Additional adverse reactions observed in children and adolescents

The same adverse reactions as in adults may also occur in children and adolescents.

The following adverse reactions have been observed more frequently in children and adolescents, or were not observed in adults:

Very common (may affect more than 1 in 10 people):

• increased blood levels of prolactin, which in rare cases may lead to:
  • breast enlargement and unexpected milk production in both boys and girls;
  • in girls, cessation of menstruation or irregular periods.
• increased appetite;
• vomiting;
• abnormal muscle movements, including difficulty initiating movement, tremors, feeling of restlessness or muscle stiffness without 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 reactions

If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions 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 181C
02-222 Warsaw
Tel: +48 22 49 201 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse reactions can also be reported to the marketing authorisation holder.

Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store KETREL XR, prolonged-release tablets

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the cardboard box and blister pack following: EXP. The expiry date refers to the last day of the specified month.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist what to do with medicines no longer required. Proper disposal will help protect the environment.
• No special storage conditions apply for this medicine.

6. Contents of the pack and other information

What KETREL XR extended-release tablets contain

• The active substance is quetiapine. Each extended-release tablet contains 50, 200, 300, or 400 mg of quetiapine (as quetiapine fumarate).
• Other ingredients are:
  Tablet core: Lactose monohydrate, hypromellose, sodium chloride, povidone K30, talc, and magnesium stearate. Additionally, 50 mg tablets contain siliconized microcrystalline cellulose.

Tablet coating: Titanium dioxide (E 171), polyethylene glycol 400.
50 mg tablets additionally contain polyvinyl alcohol, talc, and iron oxide red (E 172).
50, 200, and 300 mg tablets additionally contain iron oxide yellow (E 172).
200, 300, and 400 mg tablets additionally contain hypromellose 6 cP.

What KETREL XR extended-release tablets look like and contents of the pack
KETREL XR 50 mg extended-release tablets: Peach-colored, round, biconvex, film-coated tablets, embossed with the code "Q50" on one side and smooth on the other.
KETREL XR 200 mg extended-release tablets: Yellow, round, biconvex, film-coated tablets, embossed with the code "I2" on one side and smooth on the other. Tablet diameter is approximately 9.6 mm.
KETREL XR 300 mg extended-release tablets: Light yellow, round, biconvex, film-coated tablets, embossed with the code "Q300" on one side and smooth on the other. Tablet diameter is approximately 11.2 mm.
KETREL XR 400 mg extended-release tablets: White, round, biconvex, film-coated tablets, embossed with the code "I4" on one side and smooth on the other. Tablet diameter is approximately 12.8 mm.

PVC/PVDC/Aluminium blisters: Packs containing 10, 30, 50, 60, and 100 tablets are registered for 200, 300, and 400 mg strengths.
PVC/PVDC/Aluminium or OPA/Aluminium/PVC/Aluminium blisters: Packs containing 6, 10, 20, 28, 30, 50, 60, 90, and 100 tablets are registered for 50 mg strength.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Celon Pharma S.A.
ul. Ogrodowa 2A, Kiełpin
05-092 Łomianki
Poland

Manufacturer/Importer:
Accord Healthcare Limited
Sage House
319 Pinner Road
North Harrow
Middlesex, HA1 4HF
United Kingdom
GAP S.A.
46, Agissialou, str.
Agios Dimitrios,
17341 Athens
Greece
For KETREL XR 50 mg extended-release tablets:
ARROW GENERIQUES - LYON
26 avenue Tony Garnier, LYON, 69007
France
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland
Accord UK Limited
Whiddon Valley
Barnstaple; Devon EX32 8NS
United Kingdom
Accord Healthcare B.V.
Winthontlaan 200
3526 KV Utrecht
The Netherlands

This medicinal product is authorised in the Member States of the European Economic Area under the following names: