Kefrenex

Leaflet accompanying the packaging: patient information

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

You should carefully read the contents of this leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• If you have any doubts, you should consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Kefrenex and what is it used for

Kefrenex contains the active substance quetiapine. It belongs to a group of medicines called antipsychotics. Kefrenex can be used to treat severe diseases such as:

• Bipolar affective disorder: the patient may constantly feel sad. The patient may have depression, feelings of guilt, lack of energy, loss of appetite, or difficulty sleeping.
• Mania: the patient may feel very strong excitement, agitation, enthusiasm, or overreactivity, or decreased critical judgment, including feelings of aggression or destructiveness.
• Schizophrenia: the patient may hear or feel things that do not exist, take things that are not true for real, or feel excessive suspicion, anxiety, confusion, guilt, tension, or depression.

Your doctor may recommend continued use of Kefrenex even if your condition improves.

2. Important information before taking Kefrenex

When not to take Kefrenex:

If any of the above situations apply to you, do not take Kefrenex. If in doubt, consult your doctor or pharmacist before taking the medicine.

Warnings and precautions

Before starting to take Kefrenex, you should discuss it with your doctor or pharmacist:

• If you have depression or other conditions that are being treated with antidepressant medicines. Taking these medicines with Kefrenex may lead to the development of serotonin syndrome, a potentially life-threatening condition (see "Kefrenex and other medicines").
• If you or your family have a history of heart disease, such as arrhythmias, heart muscle weakness, or myocarditis, or if you are taking any medicines that may affect your 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 a seizure (epilepsy).
• If you have diabetes or are at risk of developing diabetes. In this case, your doctor may recommend glucose tests while taking Kefrenex.
• If you have ever had a low white blood cell count (regardless of whether it was caused by taking other medicines or not).
• If you are an elderly person with dementia (reduced cognitive function). In this case, you should not take Kefrenex, as the group of medicines to which quetiapine belongs may increase the risk of stroke and sometimes the risk of death in elderly patients with dementia.
• If you are elderly and have Parkinson's disease/parkinsonism.
• If you or your family have a history of venous thrombosis, as taking medicines from this group can cause them to form.
• If you have a condition where you stop breathing for short periods during normal nighttime sleep (called "sleep apnea") and you are taking medicines that slow down normal brain activity (i.e., "depressant" medicines).
• If you have a condition where you cannot completely empty your bladder, have an enlarged prostate, intestinal obstruction, or increased eye pressure. These symptoms may be caused by medicines (called "anticholinergic" medicines) used to treat various diseases that affect nerve cell function.
• If you have been addicted to alcohol or drugs in the past.

You should immediately inform your doctor if you experience any of the following symptoms after taking Kefrenex:

• Rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or unexplained fatigue. Your doctor will need to examine your heart and, if necessary, refer you to a cardiologist immediately.
• High fever, increased muscle stiffness, sweating, or decreased consciousness (a condition called malignant neuroleptic syndrome), which occur simultaneously. Immediate medical attention may be necessary.
• Uncontrolled movements, mainly in the face and tongue.
• Dizziness or a feeling of heavy sleepiness. This may increase the risk of accidental injury or bruising (due to falls) in elderly patients.
• Seizures.
• Prolonged, painful erection (priapism).

Such symptoms may be caused by antipsychotic medicines. You should immediately inform your doctor if:

• You have a fever, flu-like symptoms, sore throat, or any other infection, as this may be due to a very low white blood cell count, which may require discontinuation of Kefrenex and/or the use of other treatments.
• You have constipation with persistent abdominal pain or constipation that does not respond to treatment, as this may lead to a very serious bowel obstruction.

Suicidal thoughts or worsening depression

If you have depression, you may sometimes experience thoughts of self-harm or suicide. These thoughts may be particularly severe at the beginning of treatment, as the medicine does not work immediately, usually only after about 2 weeks, and sometimes even later. Such thoughts may also worsen if you suddenly stop taking the medicine. These thoughts may occur, especially if you are a young adult. Clinical trials have shown an increased risk of suicidal thoughts and/or behaviors in young adults under 25 years of age with depression. If you experience thoughts of self-harm or suicide, you should immediately contact your doctor or go to the hospital. You can tell someone in your family or a close person about your depression and show them this leaflet, asking them to read it. You can ask this person to tell you if they notice any worsening of depressive symptoms or other worrying changes in behavior.

Severe skin reactions

During treatment with Kefrenex, very rare severe skin reactions have been reported, which can be life-threatening or fatal. They usually manifest as:

• Stevens-Johnson syndrome (SJS), a widespread rash with blisters on the skin, especially around the mouth, nose, eyes, and genitals.
• Toxic epidermal necrolysis (TEN), a more severe form causing widespread skin peeling.
• Drug reaction with eosinophilia and systemic symptoms (DRESS) involving flu-like symptoms with a rash, fever, swollen lymph nodes, and abnormal blood test results (including increased white blood cell count (eosinophilia) and liver enzyme activity).

If you experience any of these symptoms, you should stop taking Kefrenex and immediately contact your doctor.

Weight gain

During treatment with quetiapine, weight gain has been observed. You and your doctor should regularly monitor your weight.

Children and adolescents

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

Kefrenex and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. You should not take Kefrenex if you are taking any of the following medicines:

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

You should inform your doctor if you are taking any of the following medicines:

• Antidepressant medicines. These medicines may interact with Kefrenex and may cause symptoms such as involuntary, rhythmic muscle contractions, including eye movements, agitation, hallucinations, coma, excessive sweating, tremors, increased reflexes, muscle stiffness, and body temperature above 38°C (serotonin syndrome). If such symptoms occur, you should consult your doctor.
• Antiepileptic medicines (such as phenytoin or carbamazepine).
• Antihypertensive medicines.
• Barbiturates (used to treat sleep disorders).
• Thioridazine or lithium (other antipsychotic medicines).
• Medicines that affect heart rhythm, such as those that can cause electrolyte imbalance (low potassium or magnesium), such as diuretics (water pills) or certain antibiotics (used to treat infections).
• Medicines that can cause constipation.
• Medicines (called "anticholinergic" medicines) used to treat various diseases that affect nerve cell function.

You should not stop taking other medicines without consulting your doctor.

Kefrenex with food, drink, and alcohol

Kefrenex can be taken with or without food. During treatment with Kefrenex, you should be cautious when consuming alcoholic beverages. Taking Kefrenex and alcohol at the same time may cause drowsiness. You should not take Kefrenex with grapefruit juice, as it may affect the way the medicine works.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine. Kefrenex should not be used during pregnancy, unless your doctor recommends it. Kefrenex should not be used during breastfeeding. The following symptoms, indicating withdrawal symptoms, may occur in newborn babies whose mothers took Kefrenex during the last trimester of pregnancy (last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If your baby experiences any of these symptoms, you may need to contact your doctor.

Driving and using machines

The tablets of the medicine you are taking may cause drowsiness. You should not drive, use tools, or operate machinery until you know how you react to the medicine.

Effect on laboratory tests

If you are taking Kefrenex and a urine test for drugs is performed, it may give a false positive result for methadone or certain antidepressant medicines called tricyclic antidepressants, even if you have not taken these medicines. In such a case, more specific tests should be performed.

Kefrenex contains lactose

Kefrenex contains lactose, a type of sugar. If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking the medicine.

Kefrenex, 25 mg contains orange yellow S (E 110)

Kefrenex, 25 mg contains a coloring agent, orange yellow S (E 110). The medicine may cause allergic reactions.

Kefrenex contains sodium

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

3. How to take Kefrenex

This medicine should always be taken as directed by your doctor or pharmacist. If you are unsure, you should consult your doctor or pharmacist. Your doctor will determine the initial dose. The maintenance dose (daily dose) will depend on your disease and needs, but it is usually a dose between 150 mg and 800 mg per day.

• The medicine should be taken once a day, in the evening, before bedtime, or twice a day, depending on your disease.
• The tablets should be swallowed whole, with water.
• The tablets can be taken with or without food.
• You should not drink grapefruit juice while taking Kefrenex, as it may affect the way the medicine works.
• You should not stop taking the tablets, even if you feel better, unless your doctor recommends it.

Liver problems

If you have liver disease, your doctor may reduce the dose of Kefrenex.

Elderly patients

If you are an elderly person, your doctor may reduce the dose of Kefrenex.

Use in children and adolescents

Kefrenex should not be used in children and adolescents under 18 years of age.

Taking a higher dose of Kefrenex than recommended

If you take a higher dose of Kefrenex than recommended by your doctor, you may experience drowsiness, fainting, or dizziness, and irregular heartbeat. You should immediately contact your doctor or the nearest hospital. You should take the remaining Kefrenex tablets with you.

Missing a dose of Kefrenex

If you miss a dose of Kefrenex, you should take it as soon as possible. If the time until the next dose is short, you should take the medicine at the usual time. You should not take a double dose of Kefrenex to make up for the missed tablet.

Stopping treatment with Kefrenex

If you suddenly stop taking Kefrenex, you may experience difficulty sleeping (insomnia) or nausea, or headaches, diarrhea, vomiting, dizziness, or irritability. Your doctor may recommend gradually reducing the dose to stop treatment. If you have any further doubts about taking this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Kefrenex can cause side effects, although not everybody gets them.

Very common: may affect more than 1 in 10 people

• Dizziness (which may cause falls), headache, dry mouth.
• Drowsiness (which may cause falls and may decrease over time, during continued treatment with Kefrenex).
• Withdrawal symptoms (symptoms that may occur after stopping Kefrenex) including difficulty sleeping (insomnia), nausea, headaches, diarrhea, vomiting, dizziness, or irritability. It is recommended to gradually stop taking the medicine over a period of at least 1 to 2 weeks.
• Weight gain.
• Abnormal muscle movements. Including difficulty starting intended muscle movements, tremors, restlessness, or muscle stiffness without pain.
• Changes in the levels of some lipids (triglycerides and total cholesterol).

Common: may affect up to 1 in 10 people

• Increased heart rate.
• Feeling of heartbeat, palpitations, or interruptions in heartbeat.
• Constipation, stomach upset (indigestion).
• Feeling of weakness.
• Swelling of hands or feet.
• Low blood pressure when changing position to standing. These may cause dizziness or fainting (which may cause falls).
• Increased blood glucose levels.
• Blurred vision.
• Unpleasant dreams and nightmares.
• Increased appetite.
• Feeling of irritability.
• Speech and language disorders.
• Suicidal thoughts and behaviors.
• Shortness of breath.
• Vomiting (mainly in elderly patients).
• Fever.
• Changes in thyroid hormone levels in the blood.
• Decreased number of some types of white blood cells.
• Increased liver enzyme activity.
• Increased prolactin levels in the blood. Increased prolactin levels may rarely lead to:
• breast swelling and unexpected milk production in men and women,
• absence of menstruation or irregular menstruation in women.

Uncommon: may affect up to 1 in 100 people

• Seizures and epileptic fits.
• Allergic reactions, including rash, skin swelling, and swelling around the mouth.
• Unpleasant sensations in the lower limbs (restless legs syndrome).
• Difficulty swallowing.
• Uncontrolled movements, mainly of the face and tongue.
• Sexual disorders.
• Diabetes.
• Changes in the electrical activity of the heart observed in the ECG (QT interval prolongation).
• Slower than normal heartbeat, which may occur at the beginning of treatment and may be associated with low blood pressure and fainting.
• Difficulty urinating.
• Fainting (which may cause falls).
• Stuffy nose.
• Decreased red blood cell count.
• Decreased sodium levels in the blood.
• Worsening of existing diabetes.

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

• Simultaneous occurrence of symptoms such as high fever, sweating, muscle stiffness, and decreased consciousness or fainting (a condition called malignant neuroleptic syndrome).
• Yellowing of the skin and eyes (jaundice).
• Hepatitis (inflammation of the liver).
• Prolonged and painful erection (priapism).
• Breast swelling and unexpected milk production.
• Menstrual disorders.
• Blood clots in the veins, especially in the legs, which can travel through the bloodstream to the lungs, causing chest pain and difficulty breathing. If you experience any of these symptoms, you should immediately consult your doctor.
• Sleepwalking, talking, eating, or other activities while sleeping (somnambulism).
• Decreased body temperature (hypothermia).
• Pancreatitis (inflammation of the pancreas).
• A condition (called metabolic syndrome) in which three or more of the following symptoms occur: increased fat in the abdominal cavity, decreased "good" cholesterol (HDL-C), increased triglyceride levels in the blood, high blood pressure, and increased blood sugar levels.
• Agranulocytosis, a condition characterized by the simultaneous occurrence of fever, flu-like symptoms, sore throat, or other infections with a very low white blood cell count.
• Bowel obstruction.
• Increased creatine kinase activity in the blood (a substance found in muscles).

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

• Increased rash, blisters, or red spots on the skin.
• Severe allergic reaction (anaphylaxis) that can cause difficulty breathing 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 genitals (Stevens-Johnson syndrome). See section 2.
• Abnormal secretion of the hormone that controls urine volume.
• Muscle fiber breakdown and muscle pain (rhabdomyolysis).

Frequency not known: frequency cannot be estimated from the available data

• Skin rash with irregular red spots (erythema multiforme).
• A severe, sudden allergic reaction with symptoms such as fever and blisters on the skin, and peeling of the skin (toxic epidermal necrolysis).
• Drug reaction with eosinophilia and systemic symptoms (DRESS) involving flu-like symptoms with a 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 took Kefrenex during pregnancy.
• Heart muscle disorders (cardiomyopathy).
• Myocarditis (inflammation of the heart muscle).
• Stroke.
• Vasculitis (inflammation of blood vessels), often with a skin rash with small red or purple spots.

Medicines in the same group as Kefrenex may cause heart rhythm disorders, which can be a serious condition and, in severe cases, even fatal. Some side effects are only observed in blood tests. These include changes in the levels of certain fats (triglycerides and total cholesterol) or sugar in the blood, changes in thyroid hormone levels in the blood, increased liver enzyme activity, decreased number of some types of blood cells, decreased red blood cell count, increased creatine kinase activity in the blood (a substance found in muscles), decreased sodium levels in the blood, and increased prolactin levels in the blood. Increased prolactin levels may rarely lead to:

• breast swelling and unexpected milk production in men and women,
• absence of menstruation or irregular menstruation in women.

Therefore, your doctor may occasionally recommend blood tests.

Additional side effects in children and adolescents

The same side effects that are observed in adult patients may also occur in children and adolescents. The following side effects have been observed more frequently in children and adolescents or have not been observed in adult patients:

Very common: may affect more than 1 in 10 people

• Increased prolactin levels in the blood. Increased prolactin levels may rarely lead to: breast swelling and unexpected milk production in both girls and boys, absence of menstruation or irregular menstruation in girls.
• Increased appetite.
• Vomiting.
• Abnormal muscle movements, including difficulty starting intended muscle movements, tremors, restlessness, or muscle stiffness without pain.
• Increased blood pressure.

Common: may affect up to 1 in 10 people

• Feeling of weakness, fainting (which may cause falls).
• Stuffy nose.
• Feeling of irritability.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help gather more information on the safety of this medicine.

5. How to store Kefrenex

Store 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 packaging after: EXP. The expiry date refers to the last day of the specified month. Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Kefrenex contains

• The active substance of Kefrenex is quetiapine.

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

• Other ingredients are:

Tablet core: hypromellose 2910, calcium hydrogen phosphate dihydrate, lactose monohydrate, cornstarch, sodium carboxymethylcellulose (Type A), magnesium stearate, microcrystalline cellulose pH 102, talc, silicon dioxide. 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 S (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: hydroxypropylcellulose, hypromellose 2910, titanium dioxide (E 171), talc.

What Kefrenex looks like and contents of the pack

Kefrenex, 25 mg: round, 5.7 mm in diameter, biconvex film-coated tablets, peach-colored. Kefrenex, 100 mg: round, 9.1 mm in diameter, biconvex film-coated tablets, yellow, with a score line on one side. Kefrenex, 200 mg: round, 12.1 mm in diameter, biconvex film-coated tablets, white, with a score line on one side. Kefrenex, 300 mg: oval, biconvex film-coated tablets, white, with a score line on one side. The 100 mg, 200 mg, and 300 mg film-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). Not all pack sizes may be marketed.

Marketing authorization holder

Aristo Pharma Sp. z o.o. ul. Baletowa 30, 02-867 Warsaw

Manufacturer

Genepharm S.A. 18 km Marathonos Avenue, 153 51 Pallini Attikis, Greece. For more information on this medicine, including its names in the Member States of the European Economic Area, you should contact the marketing authorization holder.

Date of last revision of the leaflet:

June 2024