Kefrenex

Package leaflet: Information for the user

Kefrenex, 25 mg, film-coated tablets
Kefrenex, 100 mg, film-coated tablets
Kefrenex, 200 mg, film-coated tablets
Kefrenex, 300 mg, film-coated tablets
Quetiapine
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

1. What Kefrenex is and what it is used for

Kefrenex contains a substance called quetiapine. It belongs to a group of medicines
known as antipsychotics. Kefrenex may be used in the treatment of serious disorders such as:

• Bipolar affective disorder: the patient may constantly feel sad, depressed, guilty, lack energy, lose appetite, or have difficulty sleeping.
• Mania: the patient may experience intense feelings of excitement, agitation, restlessness, enthusiasm, or hyper-reactivity, or have reduced ability to make critical judgments, including feelings of aggression or destructiveness.
• Schizophrenia: the patient may hear or sense things that are not real, believe things that are not true, or experience excessive suspiciousness, anxiety, confusion, guilt, tension, or depression.

Your doctor may recommend continuing treatment with Kefrenex even if your condition improves.

2. Information before using Kefrenex

When not to use Kefrenex:

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

If any of the situations listed above apply to the patient, Kefrenex must not be used.
If in doubt, consult a doctor or pharmacist before taking this medicine.

Warnings and precautions

Before starting treatment with Kefrenex, discuss the following with your doctor or pharmacist:

• If the patient has depression or other conditions treated with antidepressant medicines. Taking these medicines together with Kefrenex may lead to the development of serotonin syndrome, a potentially life-threatening condition (see "Kefrenex with other medicines").
• If the patient has or has had any heart conditions, such as irregular heartbeat, weakened heart muscle, or myocarditis, either personally or in the family, or if the patient is taking any medicines that may affect heart rhythm.
• If the patient has low blood pressure.
• If the patient has had a stroke, particularly if elderly.
• If the patient has liver problems.
• If the patient has ever had seizures (epilepsy).
• If the patient has diabetes or an increased risk of developing diabetes. In such cases, the doctor may recommend blood glucose monitoring during treatment with Kefrenex.
• If the patient has ever had a low white blood cell count (regardless of whether it was caused by other medicines or not).
• If the patient is an elderly person with dementia (impaired brain function). In such cases, the patient should not take Kefrenex, as the class of medicines to which quetiapine belongs may increase the risk of stroke and, in some cases, risk of death in elderly patients with dementia.
• If the patient is elderly and suffers from Parkinson’s disease/parkinsonism.
• If the patient has or has had venous thrombosis (blood clots) in the family, as use of medicines in this group may promote their formation.
• If the patient has or has had a condition involving brief periods of stopped breathing during normal sleep (called "sleep apnoea") and is taking medicines that slow down normal brain activity (i.e. "depressants").
• If the patient has or has had difficulty completely emptying the bladder (urinary retention), an enlarged prostate, intestinal obstruction, or increased pressure inside the eye. These symptoms may be caused by medicines (called "anticholinergics") used to treat various diseases affecting nerve cell function.
• If the patient has previously been addicted to alcohol or drugs.

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

• 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.
• High temperature (fever), severe muscle stiffness, sweating, or decreased level of consciousness (a condition called neuroleptic malignant syndrome). These symptoms may require immediate medical attention.
• Uncontrolled movements, mainly of the face and tongue.
• Dizziness or feeling very drowsy. This may increase the risk of accidental injury or falls, especially in elderly patients.
• Seizures.
• Prolonged, painful erection (priapism).

These symptoms may be caused by antipsychotic medicines.

Immediately inform the doctor if:

• The patient develops fever, flu-like symptoms, sore throat, or any other infection, as this may indicate a very low white blood cell count, which may require stopping treatment with Kefrenex and/or starting alternative treatment.
• The patient has constipation accompanied by persistent abdominal pain or constipation that does not respond to treatment, as this may lead to a very serious intestinal obstruction.

Suicidal thoughts or worsening depression

If the patient has depression, suicidal thoughts or thoughts of self-harm may sometimes occur. These thoughts may be particularly pronounced at the beginning of treatment, as the medicine does not work immediately and usually takes about 2 weeks, sometimes longer. These thoughts may also increase if the patient suddenly stops taking the medicine. Such thoughts may occur, particularly in young adults. Clinical studies have shown an increased risk of suicidal thoughts and/or behaviour in young adults under 25 years of age with depression.

If thoughts of self-harm or suicide occur, contact a doctor immediately or go to a hospital. The patient may wish to inform a family member or close friend about their depression and show them this leaflet, asking them to read it. The patient may ask this person to inform them if they notice worsening of depressive symptoms or other worrying changes in behaviour.

Severe skin reactions

Very rarely, severe skin reactions have been reported during treatment with Kefrenex, which may be life-threatening or lead to death. These usually manifest as:

• Stevens-Johnson syndrome (SJS), a widespread blistering rash on the skin, particularly around the mouth, nose, eyes, and genital area,
• Toxic epidermal necrolysis (TEN), a more severe form causing extensive skin peeling,
• Drug reaction 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 elevated liver enzymes).

If any of the above symptoms occur, stop taking Kefrenex immediately and contact a doctor without delay.

Weight gain

Weight gain has been observed during treatment with quetiapine. The patient and their doctor should regularly monitor body weight.

Children and adolescents

Kefrenex is not intended for use in children and adolescents under 18 years of age.

Kefrenex with other medicines

Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take.

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

• Certain medicines used to treat HIV.
• Azole antifungals (used to treat fungal infections).
• Erythromycin or clarithromycin (used to treat infections).
• Nefazodone (used to treat depression).

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

• Antidepressants. These medicines may interact with Kefrenex and may cause symptoms such as involuntary, rhythmic muscle contractions (including eye movements), agitation, hallucinations, coma, excessive sweating, tremor, increased reflexes, increased muscle tension, and body temperature above 38°C (serotonin syndrome). If such symptoms occur, consult a doctor.
• Antiepileptic medicines (such as phenytoin or carbamazepine).
• Antihypertensive medicines.
• Barbiturates (medicines used for sleep disorders).
• Thioridazine or lithium (other antipsychotic medicines).
• Medicines that affect heart rhythm, e.g. medicines that may cause electrolyte imbalance (low potassium or magnesium levels), such as diuretics (water tablets) or certain antibiotics (medicines used to treat infections).
• Medicines that may cause constipation.
• Medicines (called "anticholinergics") used to treat various diseases affecting nerve cells.

Do not stop taking other medicines without informing your doctor.

Kefrenex, food, drink, and alcohol

Kefrenex may be taken with or without food.

During treatment with Kefrenex, caution should be exercised when consuming alcoholic beverages.
Concomitant use of Kefrenex and alcohol may cause drowsiness.

Do not take Kefrenex with grapefruit juice. This may affect how the medicine works.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before taking this medicine.

Kefrenex should not be used during pregnancy unless specifically advised by a doctor. Kefrenex should not be used during breastfeeding.

The following withdrawal symptoms may occur in newborns whose mothers have taken Kefrenex 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 using machines

The tablets taken by the patient may cause drowsiness. The patient should not drive, use tools, or operate machinery until they know how the medicine affects them.

Effect on drug screening tests

If the patient taking Kefrenex undergoes a urine test for drugs of abuse, it may give a false positive result for methadone or certain antidepressants called tricyclic antidepressants, even if the patient has not taken these medicines. In such cases, more specific and confirmatory tests should be performed.

Kefrenex contains lactose

Kefrenex contains lactose, a type of sugar. If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.

Kefrenex 25 mg contains sunset yellow (E 110)

Kefrenex 25 mg contains the colouring agent sunset yellow (E 110). This medicine may cause allergic reactions.

Kefrenex contains sodium

Kefrenex contains less than 1 mmol (23 mg) of sodium per 25 mg, 100 mg, 200 mg, 300 mg tablet, meaning the medicine is considered "sodium-free".

3. How to use Kefrenex

This medicine should always be taken exactly as directed by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
The treating physician will determine the initial dose.
The maintenance dose (daily dose) will depend on the patient's condition and individual needs, but
will usually range between 150 mg and 800 mg per day.

• The medicine should be taken once daily, in the evening before bedtime, or twice daily, depending on the patient's condition.
• Tablets should be swallowed whole with water.
• Tablets may be taken with or without food.
• Grapefruit juice should not be consumed during treatment with Kefrenex, as it may affect the medicine's action.
• Do not discontinue taking the tablets, even if symptoms improve, unless advised by the doctor.

Liver problems
If the patient has liver disease, the doctor may reduce the dose of the medicine.
Elderly patients
If the patient is elderly, the doctor may reduce the dose of the medicine.
Use in children and adolescents
Kefrenex should not be used in children and adolescents under 18 years of age.
Taking more Kefrenex than prescribed
If more Kefrenex is taken than prescribed, symptoms such as drowsiness, fainting, dizziness, or irregular heartbeat may occur. Seek immediate medical advice from a doctor or the nearest hospital. Bring any remaining tablets of Kefrenex with you.
Missed dose of Kefrenex
If a dose has been missed, take it as soon as possible. If it is almost time for the next dose, take the next dose at the usual time. Do not take a double dose of Kefrenex to make up for a missed tablet.
Stopping Kefrenex
If Kefrenex is stopped abruptly, difficulty sleeping (insomnia), nausea, headache, diarrhoea, vomiting, dizziness, or irritability may occur. The doctor may recommend gradually reducing the dose to discontinue 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.

Very common: may affect more than 1 in 10 patients

• Dizziness (which may lead to falls), headache, dry mouth.
• Somnolence (which may lead to falls and may diminish over time during continued treatment with Kefrenex).
• Withdrawal symptoms (symptoms that may occur after discontinuation of Kefrenex), including difficulty falling asleep (insomnia), nausea, headache, diarrhoea, vomiting, dizziness, or irritability. Gradual discontinuation of the medicine over a period of at least 1 to 2 weeks is recommended.
• Weight gain.
• Abnormal muscle movements, including difficulty initiating voluntary muscle movements, tremors, restlessness, or muscle stiffness without concomitant pain.
• Changes in levels of certain lipids (triglycerides and total cholesterol).

Common: may affect up to 1 in 10 patients

• Rapid heartbeat.
• Palpitations, awareness of heartbeat, or irregular heartbeat.
• Constipation, stomach discomfort (dyspepsia).
• Feeling of weakness.
• Swelling of hands or feet.
• Low blood pressure upon standing (orthostatic hypotension), which may cause dizziness or fainting (which may lead to falls).
• Increased blood glucose levels.
• Blurred vision.
• Unpleasant dreams and nightmares.
• Increased feeling of hunger.
• Feeling of irritability.
• Speech and language disturbances.
• Suicidal thoughts and suicidal behaviour.
• Shortness of breath.
• Vomiting (mainly in elderly patients).
• Fever.
• Changes in levels of thyroid hormones in blood.
• Decreased count of certain types of white blood cells.
• Increased liver enzyme activity in blood.
• Increased blood levels of prolactin hormone. Elevated prolactin levels in blood may rarely lead to:
  • breast enlargement and unexpected milk production from the breasts in both men and women,
  • absence of menstruation or irregular menstruation in women.

Uncommon: may affect up to 1 in 100 patients

• Seizures and epileptic fits.
• Hypersensitivity reactions, including nodular rash, skin swelling, and swelling around the mouth.
• Unpleasant sensations in the lower limbs (so-called restless legs syndrome).
• Difficulty swallowing.
• Involuntary movements, mainly of the face and tongue.
• Sexual dysfunction.
• Diabetes.
• Changes in the electrical activity of the heart observed in ECG (prolongation of QT interval).
• Slower than usual heartbeat, which may occur at the beginning of treatment and may be associated with low blood pressure and fainting.
• Difficulty in urination.
• Fainting (which may lead to falls).
• Nasal congestion.
• Decreased number of red blood cells.
• Decreased sodium levels in blood.
• Worsening of pre-existing diabetes.

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

• Concurrent occurrence of symptoms such as high fever, sweating, muscle stiffness, drowsiness or fainting (a condition known as "neuroleptic malignant syndrome").
• Yellowing of the skin and eyes (jaundice).
• Inflammation of the liver (hepatitis).
• Prolonged and painful erection (priapism).
• Breast enlargement and unexpected milk production (galactorrhea).
• Menstrual disorders.
• Blood clots in veins, especially in the legs (symptoms include leg swelling, pain, and redness), which may travel through blood vessels to the lungs, causing chest pain and breathing difficulties. If any of these symptoms occur, immediate medical advice should be sought.
• Sleepwalking, talking, eating, or other activities during sleep (somnambulism).
• Decreased body temperature (hypothermia).
• Inflammation of the pancreas.
• A condition (called metabolic syndrome) in which three or more of the following may occur: increased abdominal fat, decreased levels of "good cholesterol" (HDL-C), increased blood triglyceride levels (a type of fat), high blood pressure, and increased blood sugar levels.
• Agranulocytosis, a condition characterized by the combination of fever, flu-like symptoms, sore throat or other infections, and very low white blood cell count.
• Intestinal obstruction.
• Increased blood creatine kinase activity (a substance present in muscles).

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

• Severe rash, blisters, or red spots on the skin.
• Severe allergic reaction (called anaphylaxis), which may cause breathing difficulties or lead to shock.
• Sudden swelling of the skin, usually around the eyes, lips, and throat (angioedema).
• Blisters on the skin, in the mouth, eyes, and genital organs (Stevens-Johnson syndrome). See section 2.
• Abnormal secretion of a hormone that controls urine volume.
• Breakdown of muscle fibres and muscle pain (rhabdomyolysis).

Frequency not known: frequency cannot be estimated from available data

• Skin rash with irregular red patches (erythema multiforme).
• Serious, sudden allergic reaction with symptoms such as fever, skin blisters, and skin peeling (toxic epidermal necrolysis).
• Drug reaction 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 cell count (eosinophilia) and liver enzyme activity). See section 2.
• Withdrawal symptoms may occur in newborns whose mothers used Kefrenex during pregnancy.
• Heart muscle disorders (cardiomyopathy).
• Inflammation of the heart muscle (myocarditis).
• Stroke.
• Inflammation of blood vessels (vasculitis), often with skin rash presenting as small red or purple nodules.

Medicines in the class to which Kefrenex belongs may cause disturbances in heart rhythm, which may be a serious condition and, in severe cases, may even 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 sugar, changes in levels of thyroid hormones in blood, increased liver enzyme activity, decreased count of certain types of white blood cells, decreased number of red blood cells, increased blood creatine kinase activity (a substance present in muscles), decreased sodium levels in blood, and increased blood prolactin levels. Elevated prolactin levels may rarely lead to:

• breast enlargement and unexpected milk production from the breasts in both men and women,
• absence of menstruation or irregular menstruation in women.

Therefore, your doctor may occasionally recommend blood tests.

Additional adverse reactions in children and adolescents

The same adverse reactions observed in adult patients 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 adult patients:

Very common: may affect more than 1 in 10 patients

• Increased blood levels of a hormone called prolactin. Elevated prolactin levels may rarely lead to:
  • breast enlargement and unexpected milk production in both girls and boys,
  • absence or irregular menstruation in girls.
• Increased appetite.
• Vomiting.
• Abnormal muscle movements, including difficulty initiating voluntary muscle movements, tremors, restlessness, or muscle stiffness without concomitant pain.
• Increased blood pressure.

Common: may affect 1 to 10 in 100 patients

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

Reporting of adverse reactions

If any adverse symptoms 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, 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 reactions can also be reported to the marketing authorization holder.

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

5. How to store Kefrenex

Keep in the original packaging.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following: EXP.
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Kefrenex contains

• The active substance is quetiapine.

Each Kefrenex coated tablet, 25 mg, contains 25 mg of quetiapine (as quetiapine fumarate).
Each Kefrenex coated tablet, 100 mg, contains 100 mg of quetiapine (as quetiapine fumarate).
Each Kefrenex coated tablet, 200 mg, contains 200 mg of quetiapine (as quetiapine fumarate).
Each Kefrenex coated tablet, 300 mg, contains 300 mg of quetiapine (as quetiapine fumarate).

• Other ingredients are:

Tablet core
Hypromellose 2910
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
Kefrenex, 25 mg
Opadry Pink 02B34304:
Iron oxide red (E 172)
Iron oxide yellow (E 172)
Hypromellose 2910
Titanium dioxide (E 171)
Macrogol 400
Orange yellow (E 110)

Kefrenex, 100 mg
Opadry Yellow 02B32696:
Iron oxide yellow (E 172)
Hypromellose 2910
Titanium dioxide (E 171)
Macrogol 400

Kefrenex, 200 mg and 300 mg
Opadry White 20A28735:
Hydroxypropyl cellulose
Hypromellose 2910
Titanium dioxide (E 171)
Talc

What Kefrenex looks like and contents of the pack
Kefrenex 25 mg: peach-coloured, round, biconvex coated tablets, 5.7 mm in diameter.
Kefrenex 100 mg: yellow, round, biconvex coated tablets, 9.1 mm in diameter, with a score line on one side.
Kefrenex 200 mg: white, round, biconvex coated tablets, 12.1 mm in diameter, with a score line on one side.
Kefrenex 300 mg: white, elongated, biconvex coated tablets, with a score line on one side.

Kefrenex 100 mg, 200 mg, and 300 mg coated tablets can be divided into equal doses.

Pack sizes:
Kefrenex 25 mg, 100 mg, 200 mg, and 300 mg: 30, 60, 90, or 120 tablets (in blisters of 10 tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Aristo Pharma Sp. z o.o.
Baletowa 30 Street
02-867 Warsaw
Poland

Manufacturer
Genepharm S.A.
18 km Marathonos Avenue
153 51 Pallini Attikis
Greece

For further information about this medicinal product and its names in the Member States of the European Economic Area, please contact the Marketing Authorisation Holder.

June 2024