Kefrenex

Package Leaflet: Information for the Patient

Kefrenex, 25 mg, coated tablets

Kefrenex, 100 mg, coated tablets

Kefrenex, 200 mg, coated tablets

Kefrenex, 300 mg, coated tablets

Quetiapine

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• In case of any doubts, consult a 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.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their 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 pack and other information

1. What is Kefrenex and what is it used for

Kefrenex contains the active substance quetiapine, which 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 reduced critical judgment, including feelings of aggression or destructiveness.
• Schizophrenia: the patient may hear or feel things that do not exist, believe in things that are not true, or feel excessive suspicion, anxiety, confusion, guilt, tension, or depression.

The doctor may recommend continued use of Kefrenex even if the patient's condition improves.

2. Important information before taking Kefrenex

When not to take Kefrenex:

• If the patient is allergic to quetiapine or any other ingredient of this medicine (listed in section 6),
• If the patient is taking any of the following medicines: certain HIV medicines, azole antifungals, erythromycin or clarithromycin (used to treat infections), or nefazodone (used to treat depression).

If any of the above situations apply to the patient, they should not take Kefrenex. In case of doubts, consult a doctor or pharmacist before taking the medicine.

Warnings and precautions

Before starting to take Kefrenex, the patient should discuss the following with their doctor or pharmacist:

• If the patient has 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 the patient or their family members have or have had any heart diseases, such as arrhythmias, heart failure, or myocarditis, 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, especially if they are elderly.
• If the patient has liver problems.
• If the patient has had a seizure (epilepsy).
• If the patient has diabetes or an increased risk of developing diabetes. In this case, the doctor may recommend glucose tests during treatment with Kefrenex.
• If the patient has ever had a low white blood cell count (regardless of whether it was caused by taking other medicines or not).
• If the patient is an elderly person with dementia (reduced cognitive function). In such cases, the patient should not take Kefrenex, as the group of medicines to which quetiapine belongs may increase the risk of stroke and, in some cases, the risk of death in elderly patients with dementia.
• If the patient is elderly and has Parkinson's disease or parkinsonism.
• If the patient or their family members have had venous thrombosis, as taking medicines from this group can cause them to occur.
• If the patient has or has had a condition characterized by short periods of breathing cessation during normal nighttime sleep (called "sleep apnea") and is taking medicines that slow down normal brain activity (i.e., "depressant" medicines).
• If the patient has or has had a condition in which they cannot completely empty their bladder, have an enlarged prostate, intestinal obstruction, or increased intraocular pressure. These symptoms may be caused by medicines (called "anticholinergic" medicines) used to treat various diseases that affect nerve cell function.
• If the patient has a history of alcohol or drug addiction.

The patient should immediately inform their doctor if they experience any of the following symptoms after taking Kefrenex:

• Rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or unexplained fatigue. The doctor will need to examine the heart and, if necessary, immediately refer the patient to a cardiologist.
• High fever, increased muscle stiffness, sweating, or decreased level of 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 drowsiness. This may increase the risk of accidental injury or bruising (due to falls) in elderly patients.
• Seizures.
• Prolonged, painful erections (priapism).

Such symptoms may be caused by antipsychotic medicines. The patient should immediately inform their doctor if:

• They 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.
• They have constipation with persistent abdominal pain or constipation that does not respond to treatment, as this may lead to a serious intestinal obstruction.

Suicidal thoughts or worsening depression

If the patient has depression, they may sometimes experience suicidal thoughts or behaviors. 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 the patient suddenly stops taking the medicine. These thoughts may occur, especially if the patient is a young adult. Clinical studies have shown an increased risk of suicidal thoughts and/or behaviors in young adults under the age of 25 with depression. If suicidal thoughts or behaviors occur, the patient should immediately contact their doctor or go to the hospital. They can tell someone in their family or a close person about their depression and show them this leaflet, asking them to read it. They can ask this person to tell them 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. These reactions 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 the patient experiences any of these symptoms, they should stop taking Kefrenex and immediately contact their doctor.

Weight gain

During treatment with quetiapine, weight gain has been observed. The patient and their doctor should regularly monitor the patient's weight.

Children and adolescents

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

Kefrenex and other medicines

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

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

The patient should inform their doctor if they are taking any of the following medicines:

• Antidepressant medicines. These medicines may interact with Kefrenex and 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, the patient should consult their 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 (urinary medicines) 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

The patient should not stop taking other medicines without informing their doctor.

Kefrenex with food, drinks, and alcohol

Kefrenex can be taken with or without food. During treatment with Kefrenex, the patient should be cautious when consuming alcoholic beverages. Concurrent use of Kefrenex and alcohol may cause drowsiness. The patient should not take Kefrenex with grapefruit juice, as it may affect the way the medicine works.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine. Kefrenex should not be used during pregnancy, unless the 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 the baby experiences any of these symptoms, medical attention may be necessary.

Driving and using machines

The patient's tablets may cause drowsiness. The patient should not drive, use tools, or operate machinery until they know how they react to the medicine.

Effect on laboratory tests

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

Kefrenex contains lactose

Kefrenex contains lactose, a type of sugar. If the patient has been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medicine.

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

Kefrenex, 25 mg contains a colorant, 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, or 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 the doctor or pharmacist. In case of doubts, the patient should consult their doctor or pharmacist. The doctor will determine the initial dose. The maintenance dose (daily dose) will depend on the patient's disease and needs but will usually be 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 the patient's disease.
• The tablets should be swallowed whole, with a glass of water.
• The tablets can be taken with or without food.
• The patient should not drink grapefruit juice while taking Kefrenex, as it may affect the way the medicine works.
• The patient should not stop taking the tablets, even if they feel better, unless their doctor recommends it.

Liver problems

If the patient has liver disease, their doctor may reduce the dose of Kefrenex.

Elderly patients

If the patient is elderly, their doctor may reduce the dose of Kefrenex.

Use in children and adolescents

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

Overdose of Kefrenex

In case of taking a higher dose of Kefrenex than recommended by the doctor, the patient may experience drowsiness, fainting, or dizziness, and irregular heartbeat. The patient should immediately contact their doctor or the nearest hospital. They should take the remaining Kefrenex tablets with them.

Missed dose of Kefrenex

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

Stopping treatment with Kefrenex

If the patient suddenly stops taking Kefrenex, they may experience difficulty sleeping (insomnia) or nausea, or headaches, diarrhea, vomiting, dizziness, or irritability. The doctor may recommend gradually reducing the dose to stop treatment. If the patient has any further doubts about taking this medicine, they should consult their 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 pauses 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 levels of some types of white blood cells.
• Increased liver enzyme activity in the blood.
• 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 an 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 high fever, sweating, muscle stiffness, and decreased consciousness (a condition called malignant neuroleptic syndrome).
• Yellowing of the skin and eyes (jaundice).
• Hepatitis (inflammation of the liver).
• Prolonged and painful erections (priapism).
• Breast swelling and unexpected milk production (galactorrhea).
• Menstrual disorders.
• Blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg), which can travel through the bloodstream to the lungs, causing chest pain and breathing difficulties. If any of these symptoms occur, the patient should immediately consult their doctor.
• Sleepwalking, talking, eating, or other activities while asleep (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 around the abdomen, 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.
• Intestinal 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 (called anaphylaxis), which can cause breathing difficulties or lead to shock.
• Sudden swelling of the skin, usually around the eyes, lips, and throat (angioedema).
• Blisters on the skin, mouth, eyes, and genitals (Stevens-Johnson syndrome). See section 2.
• Abnormal secretion of the hormone that controls urine volume.
• Muscle breakdown and muscle pain (rhabdomyolysis).

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

• Rash with irregular red spots (erythema multiforme).
• 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 from the same group as Kefrenex may cause heart rhythm disorders, which can be a serious condition and, in severe cases, lead to death. Some side effects are only observed in blood tests. These include changes in the levels of some fats (triglycerides and total cholesterol) or blood sugar, changes in thyroid hormone levels in the blood, increased liver enzyme activity, decreased levels 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

The doctor may occasionally recommend blood tests to monitor these side effects.

Additional side effects in children and adolescents

The same side effects that occur in adults 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 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 the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181 C, 02-222 Warsaw, phone: 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, more information can be collected on the safety of the medicine.

5. How to store Kefrenex

Store in the original package. The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the package after EXP. The expiry date refers to the last day of the month stated. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Kefrenex contains

• The active substance of Kefrenex is quetiapine.

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

• 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 anhydrous. 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 coated tablets, pink in color. Kefrenex, 100 mg: round, 9.1 mm in diameter, biconvex coated tablets, yellow in color, with a score line on one side. Kefrenex, 200 mg: round, 12.1 mm in diameter, biconvex coated tablets, white in color, with a score line on one side. Kefrenex, 300 mg: oval, biconvex coated tablets, white in color, with a score line on one side. The 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). 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