Byannli 1,000 mg prolonged-release injectable suspension in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

BYANNLI 700 mg prolonged-release injectable suspension in a prefilled syringe

BYANNLI 1 000 mg prolonged-release injectable suspension in a prefilled syringe

paliperidone

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet; you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What BYANNLI is and what it is used for
2. What you need to know before using BYANNLI
3. How to use BYANNLI
4. Possible adverse effects
5. How to store BYANNLI
6. Contents of the pack and other information

1. What BYANNLI is and what it is used for

BYANNLI contains the active substance paliperidone, which belongs to a class of medicines called antipsychotics.

BYANNLI is used as maintenance treatment to manage the symptoms of schizophrenia in adult patients.

If you have responded well to treatment with monthly or quarterly paliperidone palmitate injection, your doctor may start you on treatment with BYANNLI.

Schizophrenia is a condition with "positive" and "negative" symptoms. Positive means an excess of symptoms that are not normally present. For example, a person with schizophrenia may hear voices or see things that do not exist (called hallucinations), have false beliefs (called delusions), or have abnormally high levels of distrust toward others. Negative refers to the absence of behaviours or emotions that are normally present. For example, a person with schizophrenia may become withdrawn and unresponsive to emotional stimuli, or may have difficulty speaking in a clear and logical way. People with this disorder may also feel depressed, anxious, guilty, or tense.

BYANNLI can relieve the symptoms of your illness and reduce the likelihood that they will return.

2. What you need to know before using BYANNLI

Do not use BYANNLI

• If you are allergic to paliperidone or to any of the other components of this medicine (listed in section 6).
• If you are allergic to risperidone.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use BYANNLI.

This medicine has not been studied in elderly patients with dementia. However, elderly patients with dementia who are treated with similar medicines may have an increased risk of stroke or death (see section 4).

All medicines have side effects, and some of the side effects of this medicine may worsen symptoms of other conditions. For this reason, it is important that you discuss with your doctor if you have any of the following conditions, which could worsen during treatment with this medicine:

• if you have Parkinson's disease
• if you have a type of dementia called "dementia with Lewy bodies"
• if you have been diagnosed with a condition whose symptoms include high body temperature and muscle rigidity (known as Neuroleptic Malignant Syndrome)
• if you have experienced spasms or sudden uncontrollable movements in your face, tongue, or other parts of the body (tardive dyskinesia)
• if you have previously had low white blood cell counts (which may or may not have been caused by other medicines)
• if you are diabetic or have a tendency toward diabetes
• if you have had breast cancer or a tumor in the pituitary gland (a gland in the brain)
• if you have heart disease or are being treated for heart conditions that may make you more prone to low blood pressure
• if you have low blood pressure when standing up or sitting up suddenly
• if you have a history of seizures
• if you have kidney problems
• if you have liver problems
• if you have prolonged and/or painful erection
• if you have difficulty regulating body temperature or experience excessive body heating
• if you have abnormally high blood levels of the hormone prolactin or a possible prolactin-dependent tumor
• if you or a family member have a history of blood clots, as antipsychotics have been associated with blood clot formation.

If you are in any of these situations, talk to your doctor, as you may need a dose adjustment or monitoring during treatment.

Rarely, a dangerously low number of a specific type of white blood cells responsible for fighting infections has been observed in patients receiving this medicine. Your doctor may decide to perform regular white blood cell counts.

Even if you have previously tolerated oral paliperidone or risperidone, allergic reactions may rarely occur after receiving BYANNLI injections. Seek immediate medical help if you experience a skin rash, throat swelling, itching, or breathing difficulties, as these may be signs of a serious allergic reaction.

This medicine may cause you to gain or lose weight. Significant weight changes could be harmful to your health. Your doctor will monitor your body weight regularly.

Since diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed in some patients taking this medicine, your doctor should monitor for possible signs of hyperglycemia. In patients with pre-existing diabetes mellitus, blood glucose levels should be monitored regularly.

Because this medicine may reduce the vomiting reflex, it could mask the body's normal response to ingesting toxic substances or other illnesses.

Cataract surgery

If you are planning eye surgery, inform your ophthalmologist that you are using this medicine, because during cataract surgery (removal of the cloudy lens of the eye):

• the pupil (the black circle in the center of the eye) may not dilate as needed
• the iris (the colored part of the eye) may become floppy during surgery, which could cause eye damage.

Children and adolescents

Do not use this medicine in children and adolescents under 18 years of age. Its safety and efficacy have not been established in these patients.

Other medicines and BYANNLI

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

If you take this medicine with carbamazepine (an antiepileptic and mood stabilizer), you may need to adjust the dose of this medicine.

Since this medicine acts mainly in the brain, using other medicines that also act on the brain could increase side effects such as drowsiness or other brain effects, including other psychiatric medicines, opioids, antihistamines, and sleep medicines.

Tell your doctor if you are taking this medicine and also taking risperidone or paliperidone orally for prolonged periods. You may need to adjust your BYANNLI dose.

Because this medicine can lower blood pressure, caution is needed when combining it with other medicines that lower blood pressure.

This medicine may reduce the effect of medicines used for Parkinson's disease and restless legs syndrome (e.g., levodopa).

This medicine may cause an abnormality in the electrocardiogram (ECG) indicating that electrical impulses take longer to reach a specific part of the heart (known as "QT interval prolongation"). Other medicines that have this effect include certain medicines used to regulate heart rhythm or treat infections, as well as other antipsychotics.

If you have a history of seizures, this medicine may increase the likelihood of having them again. Other medicines with this effect include certain antidepressants, antibiotics, and other antipsychotics.

BYANNLI should be used with caution with medicines that increase central nervous system activity (psychostimulants such as methylphenidate).

Use of BYANNLI with alcohol

Alcohol should be avoided.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Women of childbearing potential

A single dose of this medicine is expected to remain in the body for up to 4 years, which could be dangerous for your child. Therefore, BYANNLI should only be used in women planning pregnancy if clearly necessary.

Pregnancy

Do not use this medicine during pregnancy without first discussing it with your doctor. Newborns of mothers who received paliperidone during the third trimester (the last three months of pregnancy) may experience the following symptoms: tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. Newborns should be closely monitored, and if your baby shows any of these symptoms, seek medical attention immediately.

Breastfeeding

This medicine can pass from mother to child through breast milk. It may be harmful to the child even long after the last dose. For this reason, you must not breastfeed while using or if you have used this medicine within the last 4 years.

Driving and using machines

During treatment with this medicine, dizziness, extreme tiredness, and vision problems (see section 4) may occur. These effects should be considered in situations requiring high attention, such as driving vehicles or operating machinery.

BYANNLI contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; hence, it is essentially "sodium-free."

3. How to use BYANNLI

This medicine is administered by a doctor or healthcare professional. Your doctor will tell you when your next injection should be given. It is important that you do not miss your scheduled dose. If you are unable to attend your appointment, make sure to call immediately to schedule another appointment as soon as possible.

You will receive one injection of BYANNLI into the buttock every 6 months.

Depending on your symptoms, your doctor may increase or decrease the amount of medicine given at your next scheduled injection.

Patients with renal disorders

If you have mild renal impairment, your doctor will determine whether BYANNLI is appropriate based on the dose of monthly or quarterly injectable palmitate of paliperidone you have been receiving. The 1,000 mg dose of BYANNLI is not recommended.

If you have moderate or severe renal impairment, you must not use this medicine.

Elderly population

If you have reduced renal function, your doctor may adjust the dose of this medicine.

If you are given more BYANNLI than you should

This medicine is administered under medical supervision; therefore, it is unlikely that you will receive more than the correct amount.

If a patient receives an excessive amount of paliperidone, the following symptoms may occur: drowsiness or sedation, increased heart rate, low blood pressure, changes in the electrocardiogram (electrical recording of the heart), or slow and abnormal movements of the face, body, arms, or legs.

If you stop treatment with BYANNLI

If you stop receiving the injections, your schizophrenia symptoms may worsen. You must not stop using this medicine unless your doctor tells you to do so.

If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Serious adverse effects

If you experience any of the following serious adverse effects, you may need immediate medical treatment. Inform your doctor or go immediately to the nearest hospital if you have:

• Blood clots in the veins, especially in the legs. This is a rare adverse effect (may affect up to 1 in 1,000 people). Symptoms include:

• swelling, pain and redness in the legs (deep vein thrombosis)

• chest pain and difficulty breathing due to blood clots that have travelled through the blood vessels to the lungs (pulmonary embolism).

• Signs of stroke, frequency unknown (cannot be estimated from available data). Symptoms include:

• sudden change in your mental state

• sudden weakness or numbness of the face, arms or legs, especially on one side of the body; or difficulty speaking, even briefly.

• Neuroleptic malignant syndrome. This is a rare adverse effect (may affect up to 1 in 1,000 people). Symptoms include:

• fever, muscle stiffness, sweating or reduced level of consciousness.

• Prolonged erections, which may be painful (priapism). This is a rare adverse effect (may affect up to 1 in 1,000 people).

• Uncontrollable jerking or rhythmic spasmodic movements of the tongue, mouth and face or other parts of your body (tardive dyskinesia). This is a less common adverse effect (may affect up to 1 in 100 people). Discontinuation of this medicine may be necessary.

• Severe allergic reaction (anaphylactic reaction), frequency unknown (cannot be estimated from available data). Symptoms include:

• fever,

• swelling of the mouth, face, lips or tongue,

• difficulty breathing,

• itching, skin rash and sometimes low blood pressure.

Even if you have previously tolerated oral risperidone or oral paliperidone, you could rarely experience allergic reactions after receiving paliperidone injections.

• Floppy iris syndrome, when the iris (the coloured part of the eye) becomes floppy during cataract surgery. This may lead to eye damage (see also “Cataract surgery” in section 2). The frequency of this adverse effect is unknown (cannot be estimated from available data).
• Stevens-Johnson syndrome or toxic epidermal necrolysis. A severe or life-threatening rash with blisters and skin peeling that may start inside and around the mouth, nose, eyes and genitals and spread to other areas of the body. The frequency of these adverse effects is unknown (cannot be estimated from available data).

Inform your doctor or go immediately to the nearest hospital if you experience any of the serious adverse effects listed above.

• Agranulocytosis, dangerously low levels of a type of white blood cells in the blood necessary to fight blood infections. The frequency of this adverse effect is unknown (cannot be estimated from available data).

Other adverse effects

Very common adverse effects: may affect more than 1 in 10 people

• difficulty falling or staying asleep.

Common adverse effects: may affect up to 1 in 10 people

• symptoms of common cold, urinary tract infection, feeling of having flu.
• BYANNLI may increase levels of a hormone called “prolactin” detectable in blood tests (which may or may not cause symptoms). When symptoms of elevated prolactin occur, they may include: (in men) breast swelling, difficulty achieving or maintaining erections or other sexual dysfunctions; (in women) breast discomfort, loss of menstrual periods or other menstrual cycle problems.
• elevated blood sugar levels, weight gain, weight loss, decreased appetite.
• irritability, depression, anxiety.
• parkinsonism: this condition may include slow or altered movement, feeling of muscle stiffness or tightness (causing jerky movements), and sometimes a sensation of “freezing” of movement that then restarts. Other signs of parkinsonism include slow shuffling gait, resting tremor, increased saliva and/or drooling, and loss of facial expressiveness.
• feeling of restlessness, drowsiness or reduced alertness.
• dystonia: a disorder involving involuntary, slow or continuous muscle contractions. Although any part of the body may be affected (and may lead to abnormal postures), dystonia often affects facial muscles, including abnormal eye, mouth, tongue or jaw movements.
• dizziness.
• dyskinesia: this disorder involves involuntary muscle movements and may include
• repetitive, spasmodic or twisting movements, or spasms.
• tremor (agitation).
• headache.
• rapid heart rate.
• high blood pressure.
• cough, nasal congestion.
• abdominal pain, vomiting, nausea, constipation, diarrhoea, indigestion, toothache.
• increased blood levels of liver transaminases.
• bone or muscle pain, back pain, joint pain.
• absence of menstrual periods.
• fever, weakness, fatigue (tiredness).
• injection site reaction, with itching, pain or swelling.

Uncommon adverse effects: may affect up to 1 in 100 people

• pneumonia, chest infection (bronchitis), respiratory tract infection, sinusitis, bladder infection, ear infection, tonsillitis, fungal nail infection,

skin infections.

• reduced number of white blood cells.
• anaemia.
• allergic reaction.
• diabetes or worsening of diabetes, increased blood insulin levels (hormone regulating blood sugar levels).
• increased appetite.
• loss of appetite leading to malnutrition and reduced body weight.
• high blood triglycerides (a type of fat), increased blood cholesterol.
• sleep disorders, euphoria (mania), decreased sexual desire, nervousness, nightmares.
• fainting, urgent desire to move certain body parts, dizziness upon standing, attention problems, speech disorders, loss or alteration of taste sensation, reduced skin sensitivity to pain and touch, tingling, prickling or numbness of the skin.
• blurred vision, eye infection or red eyes, dry eyes.
• sensation of spinning (vertigo), ringing in the ears, ear pain.
• interruption of conduction between upper and lower parts of the heart, cardiac conduction disorders, QT interval prolongation on the electrocardiogram (ECG), rapid heartbeat upon standing, slow heart rate, abnormalities in the heart's electrical recording (electrocardiogram or ECG), sensation of palpitations or fluttering in the chest (palpitations).
• low blood pressure, orthostatic hypotension (due to this effect, some people treated with this medicine may feel weak, dizzy, or may faint when standing up or sitting up suddenly).
• difficulty breathing, sore throat, nosebleeds.
• abdominal discomfort, gastric or intestinal infection, difficulty swallowing, dry mouth, excessive gas or flatulence.
• increased GGT (a liver enzyme called gamma-glutamyl transferase) in the blood, increased liver enzymes in the blood.
• appearance of hives (or urticaria), itching, rash, hair loss, eczema, dry skin, skin redness, acne, subcutaneous abscess, skin peeling, scalp or skin itching.
• increased CPK (creatine phosphokinase), an enzyme in the blood.
• muscle spasms, joint stiffness, muscle weakness.
• urinary incontinence, frequent urination, pain during urination.
• erectile dysfunction, ejaculation disorders, absence of menstrual periods or cycle alterations (in women), breast development in males, sexual dysfunction, breast pain, milk production from the breasts.
• swelling of the face, mouth, eyes or lips, body swelling, swelling of arms or legs.
• increased body temperature.
• changes in walking pattern.
• chest pain, chest discomfort, general malaise.
• hardening of the skin.
• falls.

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

• eye infection.
• skin inflammation caused by mites.
• increased eosinophils (a type of white blood cells) in the blood.
• reduced platelet count (cells necessary to stop bleeding).
• inappropriate secretion of a hormone controlling urine volume.
• presence of sugar in the urine.
• potentially life-threatening complications of uncontrolled diabetes.
• low blood sugar.
• excessive water intake.
• confusion.
• lack of movement or response while awake (catatonia).
• sleepwalking.
• absence of emotions.
• inability to achieve orgasm.
• lack of response to stimuli, loss of consciousness, decreased level of consciousness, seizures (epileptic fits), balance disorder.
• abnormal coordination.
• glaucoma (increased internal eye pressure).
• eye movement disorders, “rolling eyes”, light sensitivity of the eyes, increased tearing, red eyes.
• uncontrollable head jerking.
• atrial fibrillation (a heart rhythm disorder), irregular heartbeat.
• flushing.
• difficulty breathing during sleep (sleep apnoea).
• pulmonary congestion, respiratory tract congestion.
• crackling lung sounds.
• wheezing.
• inflammation of the pancreas.
• swelling of the tongue.
• faecal incontinence, passage of very hard stools, intestinal obstruction.
• cracked lips.
• drug-related skin rash, skin thickening, dandruff.
• joint swelling.
• muscle breakdown (“rhabdomyolysis”).
• inability to urinate.
• breast discomfort, swelling of mammary glands, breast enlargement.
• vaginal discharge.
• very low body temperature, chills, sensation of thirst.
• medication withdrawal symptoms.
• pus accumulation due to infection at the injection site, deep skin layer infection, cyst at the injection site, bruising (contusions) at the injection site.

Frequency not known: cannot be estimated from available data

• ingestion of dangerously excessive amounts of water.
• sleep-related eating disorder.
• coma due to uncontrolled diabetes.
• shallow and rapid breathing, pneumonia caused by aspiration of food, voice changes.
• reduced oxygen supply to parts of the body (due to reduced blood flow).
• lack of intestinal movement causing intestinal obstruction.
• yellowing of the skin and eyes (jaundice).
• skin discoloration.
• abnormal posture.
• newborns whose mother has taken BYANNLI during pregnancy may experience adverse effects from the medicine and/or withdrawal symptoms such as irritability, slow or sustained muscle contractions, tremors, insomnia, breathing or feeding problems.
• decreased body temperature.
• accumulation of dead skin cells around the injection site, ulcer at the injection site.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of BYANNLI

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton. The expiry date is the last day of the month indicated.

Transport and store in a horizontal position. Check the correct orientation using the arrows on the product carton.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of BYANNLI

The active substance is paliperidone.

Each pre-filled syringe of BYANNLI 700 mg contains 1,092 mg of paliperidone palmitate, equivalent to 700 mg of paliperidone.

Each pre-filled syringe of BYANNLI 1,000 mg contains 1,560 mg of paliperidone palmitate, equivalent to 1,000 mg of paliperidone.

The other components are:

Polysorbate 20
Polyethylene glycol 4,000
Monohydrate citric acid
Monohydrate sodium dihydrogen phosphate
Sodium hydroxide (for pH adjustment)
Water for injections

Appearance of the product and contents of the pack

BYANNLI is a white to off-white, prolonged-release injectable suspension supplied in a pre-filled syringe. The pH is approximately 7.0. The doctor or nurse must shake the syringe vigorously to homogenize the suspension before injection.

Each pack contains 1 pre-filled syringe and 1 needle.

Marketing Authorization Holder

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer responsible for production

Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorization Holder.

Date of the most recent revision of this leaflet:

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu, and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

Information intended for healthcare professionals

This information is intended solely for healthcare professionals, who should read it together with the complete product information (Summary of Product Characteristics).

Important safety summary

1. After injection Protect the needle

After the injection, use your thumb or a flat surface to activate the needle safety device.

The needle is secured when you hear a "click".

Dispose of properly and check the injection site

Dispose of the syringe in an authorized container for sharp objects.

There may be a small amount of blood or fluid at the injection site. Apply pressure to the skin with a cotton ball or gauze until bleeding stops. Do not rub the injection site.

If necessary, cover the injection site with a bandage.