Kwetaplex xr: detailed information

Patient Information Leaflet

Kwetaplex XR, 600 mg, prolonged-release tablets
Quetiapinum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

Keep this leaflet for future reference.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are similar.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents:

What is Kwetaplex XR and what is it used for
Important information before taking Kwetaplex XR
How to take Kwetaplex XR
Possible side effects
How to store Kwetaplex XR
Contents of the pack and other information

1. What is Kwetaplex XR and what is it used for

Kwetaplex XR contains a substance called quetiapine. It belongs to a group of medicines
known as antipsychotics. Kwetaplex XR may be used to treat conditions such as:

depression in bipolar affective disorder and major depressive episodes in major depression, when the patient feels intense sadness or despair, experiences guilt, lack of energy and appetite, or has sleep disturbances;
mania: when the patient may be highly agitated, excited, enthusiastic, overly active, or have impaired critical judgment, including aggressive behavior or destructive actions;
schizophrenia, when the patient hears or senses things that do not exist; believes in things that are not true, is excessively suspicious, fearful, anxious, confused, or experiences feelings of guilt, tension, or depression.

In the treatment of major depressive episodes in major depression, Kwetaplex XR
will be used in combination with another medicine.
Your doctor may recommend continuing treatment with Kwetaplex XR even if your condition improves.

2. Important information before using Kwetaplex XR

When not to take Kwetaplex XR:

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 concomitantly: certain medicines used in HIV infection, azole antifungals, erythromycin or clarithromycin (used in infections), nefazodone (used in the treatment of depression).

If in doubt, consult a doctor or pharmacist before using Kwetaplex XR.

Warnings and precautions

Before starting treatment with Kwetaplex XR, discuss with your doctor if:

the patient has or has had heart diseases, such as cardiac arrhythmias; weakened heart muscle or myocarditis, or if the patient is taking medicines that may cause changes in heart rhythm;
the patient has low blood pressure;
the patient has had a stroke, especially if elderly;
the patient has liver problems;
the patient has ever had seizures (epilepsy);
the patient has diabetes or an increased risk of developing diabetes. In this case, the doctor may recommend monitoring blood glucose levels during treatment with Kwetaplex XR;
the patient has ever had a low white blood cell count (regardless of whether it was caused by taking other medicines or not);
the patient is an elderly person with dementia (impaired brain function). Such patients should not take Kwetaplex XR, as medicines in this class may increase the risk of stroke and sometimes risk of death in these patients;
if the patient is an elderly person with Parkinson's disease/parkinsonism;
the patient or a family member has a history of blood clots, as taking medicines in this group may promote their formation;
if the patient has or has had episodes of breathing cessation during normal sleep (so-called sleep apnoea) and is taking medicines that reduce normal brain activity (so-called antidepressants);
if the patient has or has had difficulty completely emptying the bladder (urinary retention), enlarged prostate, intestinal obstruction, or increased intraocular pressure. These symptoms may sometimes be caused by medicines (so-called anticholinergic medicines) used to treat certain disorders affecting nerve cell function;
if the patient has or has had problems with alcohol or drug abuse;
if the patient has depression or other conditions treated with antidepressants. Taking these medicines together with Kwetaplex XR may lead to the development of serotonin syndrome, a potentially life-threatening condition (see "Kwetaplex XR and other medicines").

Seek immediate medical advice if any of the following symptoms occur after taking Kwetaplex XR:

combination of fever, muscle stiffness, sweating, or decreased level of consciousness (a condition called neuroleptic malignant syndrome). Immediate medical help may be required;
involuntary movements, especially of facial muscles or tongue;
dizziness, feeling of excessive drowsiness. This may increase the risk of accidental injuries (falls) in elderly patients;
seizure (convulsion);
prolonged and painful erection (priapism);
rapid or irregular heartbeat, even at rest, palpitations, shortness of breath, chest pain, or unexplained fatigue. The doctor will need to examine the heart and, if necessary, refer the patient immediately to a cardiologist.

All these symptoms may occur during treatment with medicines in this therapeutic class.

Inform the doctor as soon as possible if any of the following symptoms occur:

fever, flu-like symptoms, sore throat, or other infections, which may result from a low white blood cell count. This may require discontinuation of Kwetaplex XR therapy and/or initiation of appropriate treatment;
constipation accompanied by persistent abdominal pain or constipation that does not respond to treatment. This may lead to severe intestinal obstruction.

Suicidal thoughts and worsening of depression
Patients with depression may sometimes have thoughts of self-harm or suicide. These symptoms or behaviours may worsen at the beginning of treatment with antidepressants, as these medicines usually take about two weeks or longer to become effective. Such thoughts may also worsen after abrupt discontinuation of the medicine. Suicidal thoughts, thoughts of self-harm or suicide are more likely to occur if the patient is a young adult. Clinical trial data indicate an increased risk of suicidal thoughts and/or suicidal behaviour in young adults under 25 years of age with depression. If the patient experiences suicidal thoughts or thoughts of self-harm, seek immediate medical help from a doctor or go to hospital. It may be helpful to inform family members or friends about the depression and ask them to read this leaflet. The patient may ask for help from family or friends and request them to inform him/her if they notice worsening depression or disturbing changes in behaviour.

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

Stevens-Johnson syndrome (SJS): widespread rash with blistering and skin peeling, especially around the mouth, nose, eyes, and genital areas;
toxic epidermal necrolysis (TEN): a more severe form causing extensive skin detachment;
drug reaction with eosinophilia and systemic symptoms (DRESS): widespread rash, high fever, elevated liver enzymes, blood abnormalities (eosinophilia), swollen lymph nodes, and involvement of other organs (also known as drug hypersensitivity syndrome);
acute generalized exanthematous pustulosis (AGEP): small pustules filled with pus;
erythema multiforme (EM): skin rash with itchy red irregular patches.

If any of these symptoms occur, discontinue quetiapine immediately and contact the treating doctor or seek medical help without delay.

Weight gain
Weight gain has been observed in patients taking Kwetaplex XR. Body weight should be monitored regularly, either by the patient or together with the doctor.

Children and adolescents
Kwetaplex XR must not be used in children and adolescents under 18 years of age.

Kwetaplex XR and other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.

Do not take Kwetaplex XR if the patient is taking:

certain medicines used in the treatment of HIV,
azole antifungals (used in fungal infections),
erythromycin or clarithromycin (used in infections),
nefazodone (used in the treatment of depression).

Inform the doctor if the patient is taking:

antiepileptic medicines (such as phenytoin or carbamazepine),
antihypertensive medicines,
barbiturates (medicines used for sleep disorders),
thioridazine or lithium (or other antipsychotics),
medicines that affect heart rhythm, for example, medicines that disturb electrolyte balance (low potassium or magnesium levels), such as diuretics (water tablets) or certain antibiotics (used in infections),
constipating medicines,
medicines (called anticholinergic medicines) that affect nerve cell function for treating certain disorders,
antidepressants. These medicines may interact with Kwetaplex XR and cause symptoms such as involuntary rhythmic muscle contractions (including eye movements), agitation, hallucinations, coma, excessive sweating, tremor, increased reflexes, increased muscle tone, and body temperature above 38°C (serotonin syndrome). If such symptoms occur, contact the doctor.

Do not stop taking other medicines without consulting a doctor.

Taking Kwetaplex XR with food, drink and alcohol
Food may interfere with the action of the medicine; therefore, Kwetaplex XR should be taken at least one hour before a meal or immediately before bedtime.

Exercise caution when consuming alcoholic beverages. Taking Kwetaplex XR together with alcohol may increase drowsiness.

Do not drink grapefruit juice during treatment with Kwetaplex XR. It may affect how the medicine works.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine. Kwetaplex XR must not be used during pregnancy unless otherwise advised by a doctor. Kwetaplex XR must not be used during breastfeeding.

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

Driving and operating machinery
Kwetaplex XR may cause drowsiness. Do not drive or operate machinery until the patient knows how the medicine affects him/her.

Effect on drug screening tests in urine
If the patient is taking Kwetaplex XR and undergoes urine drug screening, some testing methods may give a false positive result for methadone or tricyclic antidepressants (TCA), even if these drugs have not been taken. In such cases, more specific testing should be performed.

Kwetaplex XR contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.

3. How to take Kwetaplex XR

This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.

The initial dose will be determined by the treating doctor. The usual daily maintenance dose of Kwetaplex XR ranges from 150 mg to 800 mg, depending on the patient's symptoms and needs.

The medicine should be taken 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 before bedtime, as directed by the doctor).

Do not consume grapefruit juice during treatment with Kwetaplex XR, as it may affect the medicine's action.

Even if the patient feels better, do not stop taking the medicine unless instructed by the doctor.

Patients with impaired liver function
The doctor may adjust the dose in patients with impaired liver function.

Elderly patients
The doctor may adjust the dose in elderly patients.

Use in children and adolescents
Kwetaplex XR must not be used in children and adolescents under 18 years of age.

Taking more than the recommended dose of Kwetaplex XR
If more than the recommended dose is taken, the patient may experience drowsiness, dizziness, or irregular heartbeat. Seek immediate medical advice from a doctor or go to the nearest hospital. Bring the medicine with you.

Missed dose of Kwetaplex XR
If the patient forgets to take a dose, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a missed dose.

Stopping Kwetaplex XR
If treatment with Kwetaplex XR is stopped abruptly, symptoms such as difficulty sleeping (insomnia), nausea, headache, diarrhoea, vomiting, dizziness or irritability may occur. The doctor may recommend gradually reducing the dose before stopping treatment.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If the patient experiences any of the adverse reactions listed below, contact a doctor IMMEDIATELY:

Very common adverse reactions (may occur in more than 1 in 10 people):
abnormal muscle movements. Difficulty initiating intended movements, tremors, restlessness, or
muscle stiffness without accompanying pain.

Common adverse reactions (may occur in up to 1 in 10 people):
suicidal thoughts and worsening of depression;
increased heart rate;
palpitations or irregular heartbeat;
constipation, indigestion.

Uncommon adverse reactions (may occur in up to 1 in 100 people):
diabetes: a condition in which the body does not produce enough insulin or body tissues are unable to use the insulin present in the body. This leads to hyperglycaemia (excess sugar in the blood). Symptoms may include excessive thirst, increased appetite with weight loss, feeling tired, drowsiness, weakness, depression, irritability, general malaise, and passing large amounts of urine;
seizures;

hypersensitivity reactions, including skin lumps and blisters, skin swelling and swelling around the mouth; uncontrolled movements, mainly of the facial muscles or tongue; changes in electrocardiographic activity visible on ECG (prolongation of the QT interval); difficulty in urinating; worsening of pre-existing diabetes.

Rare adverse reactions (may occur in up to 1 in 1000 people):
very high body temperature (fever), excessive sweating, muscle stiffness, drowsiness or fainting (a condition known as "neuroleptic malignant syndrome");
pancreatitis, causing severe abdominal and back pain;
yellowing of the skin and eyes (jaundice);
dark-coloured urine, particularly when associated with unusual tiredness or fever (symptoms of liver inflammation);
prolonged and painful erection (priapism);
venous thrombosis, particularly in the lower limbs (symptoms include swelling, pain and redness in the legs), which may travel via blood vessels to the lungs, causing chest pain and breathing difficulties;
fever, flu-like symptoms, sore throat, infections with a very low number of white blood cells in the blood (so-called agranulocytosis);
intestinal obstruction.

Very rare adverse reactions (may occur in up to 1 in 10,000 people):

severe allergic (anaphylactic) reactions, which may cause breathing difficulties or shock;
severe rash, blisters, red spots on the skin;
rapidly developing swelling of the skin, usually around the eyes, mouth or throat (angioedema); blisters appearing on the skin, in the mouth, eyes and genitals (Stevens-Johnson syndrome). See section 2.; abnormal secretion of the hormone regulating urine volume; rhabdomyolysis (breakdown of striated muscles) and muscle pain.

Frequency not known (frequency cannot be estimated from available data):
rash with irregular red patches (erythema multiforme). See section 2.;
severe, sudden allergic reaction with symptoms such as fever and skin blisters, skin peeling (toxic epidermal necrolysis). See section 2.;
drug reaction with eosinophilia and systemic symptoms (DRESS). Widespread rash, high body temperature, increased liver enzyme activity, blood disorders (eosinophilia), swollen lymph nodes and involvement of other organs (drug reaction with eosinophilia and systemic symptoms is also known as DRESS or drug hypersensitivity syndrome) (frequency not known). If the patient develops these symptoms, quetiapine treatment must be discontinued and immediate contact made with the treating physician or medical help sought.
sudden appearance of red skin areas covered with small pustules (small blisters filled with whitish-yellow fluid), known as acute generalised exanthematous pustulosis (AGEP). See section 2.;
heart muscle disorders (cardiomyopathy);
inflammation of the heart muscle;
stroke.

Other possible adverse reactions:

Very common adverse reactions (may occur in more than 1 in 10 people):
dizziness (which may lead to falls), headache, dry mouth;
drowsiness (may diminish during continued use of this medicine) (may lead to falls);
withdrawal symptoms (symptoms which may occur after stopping this medicine), including difficulty falling asleep (insomnia), nausea, headache, diarrhoea, vomiting, dizziness or irritability. Gradual discontinuation of the medicine over 1–2 weeks is recommended;
weight gain;
changes in levels of certain lipids (triglycerides, total cholesterol).

Common adverse reactions (may occur in up to 1 in 10 people):
feeling of weakness;
swelling of hands or feet;
low blood pressure upon standing. These may cause dizziness or fainting (may lead to falls);
increased blood glucose levels;
blurred vision;
unpleasant dreams and nightmares;
increased appetite;
feeling irritable;
speech disorders;
shortness of breath;
vomiting (mainly in elderly patients);
fever;
changes in thyroid hormone activity in blood;
changes in the number of certain types of blood cells;
increased liver enzyme activity;
increased blood prolactin levels – in rare cases this may lead to:

breast swelling and unexpected milk production, in both women and men;
absence or irregular menstruation in women.

Uncommon adverse reactions (may occur in up to 1 in 100 people):
unpleasant sensations in the lower limbs (so-called restless legs syndrome);
difficulty swallowing;
sexual dysfunction;
low heart rate, which may occur at the beginning of treatment and lead to low blood pressure and loss of consciousness;
fainting (may lead to falls);
nasal congestion;
decreased number of red blood cells;
decreased serum sodium concentration;
neutropenia;
confusion.

Rare adverse reactions (may occur in up to 1 in 1000 people):
breast swelling and unexpected milk production (galactorrhoea);
menstrual disorders;
walking, talking, eating or performing other activities during sleep;
low body temperature (hypothermia);
"metabolic syndrome", in which 3 or more of the following symptoms occur together: abdominal obesity, decreased levels of "good cholesterol" (HDL-C), increased triglyceride levels, increased blood pressure and increased blood glucose;
increased blood creatine phosphokinase activity.

Frequency not known (frequency cannot be estimated from available data):
in newborns whose mothers took quetiapine during pregnancy, withdrawal symptoms may occur;
inflammation of blood vessels (vasculitis), often with skin rash presenting as small red or purple nodules.

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

Some adverse reactions are detected during laboratory blood tests. These include changes in levels of certain lipids (triglycerides and total cholesterol) or blood glucose, changes in blood thyroid hormone levels, increased liver enzyme activity, decreased number of certain types of blood cells, decreased number of red blood cells, increased blood creatine phosphokinase activity (a substance in muscles), decreased blood sodium concentration, and elevated blood prolactin levels.

Increased prolactin levels rarely may lead to:

breast swelling and unexpected milk production, in both women and men;
absence or irregular menstruation in women.

The doctor may recommend periodic monitoring tests.

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

The following adverse reactions occurred more frequently in children and adolescents than in adult patients or were observed only in children and adolescents:

Very common adverse reactions (may occur in more than 1 in 10 people):
increased prolactin levels, which may rarely lead to:

breast swelling and unexpected milk production, in both girls and boys;
absence or irregular menstruation in girls;
increased appetite;
vomiting;
abnormal muscle movements, including difficulty initiating intended movements, tremors, restlessness or muscle stiffness without accompanying pain;
increased blood pressure.

Common adverse reactions (may occur in up to 1 in 10 people):
feeling of weakness, fainting (may lead to falls);
nasal congestion;
feeling irritable.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions 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.: 22 49-21-301, fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Kwetaplex XR

Keep this medicine out of the sight and reach of children.
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 the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Kwetaplex XR contains

The active substance is quetiapine. Each extended-release tablet contains 600 mg of quetiapine (as quetiapine fumarate).
Other ingredients are: tablet core: methacrylic acid-ethyl acrylate copolymer (1:1) (type A), lactose (SD 250), maltose, talc, magnesium stearate; coating: methacrylic acid-ethyl acrylate copolymer (1:1) (type A), triethyl citrate.

What Kwetaplex XR looks like and contents of the pack
Kwetaplex XR 600 mg are white, oval, biconvex extended-release tablets, 22.7 mm in length, 10.2 mm in width, and 8.1 mm in thickness, with the engraved mark "600" on one side.
Each pack contains 60 extended-release tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Tel: +48 22 732 77 00

Manufacturer:
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Pharmathen International S.A.
Industrial Park Sapes,
Rodopi Prefecture, Block No 5
Rodopi 69300
Greece
Pharmathen S.A.
Dervenakion 6
Pallini 15351
Attiki
Greece