Product Information for the User

TREVICTA 175 mg Long-Acting Injectable Suspension

TREVICTA 263 mg Long-Acting Injectable Suspension

TREVICTA 350 mg Long-Acting Injectable Suspension

TREVICTA 525 mg Long-Acting Injectable Suspension

paliperidone

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. See section 4.

TREVICTA contains the active ingredient paliperidone, which belongs to the class of antipsychotic medications and is used as maintenance treatment to combat symptoms of schizophrenia in adult patients.

If you have responded well to treatment with palmitate paliperidone injectable administered once a month, your doctor may decide to initiate treatment with TREVICTA.

Schizophrenia is a disorder with "positive" and "negative" symptoms. Positive means an excess of symptoms that are normally not present. For example, a person with schizophrenia may hear voices or see things that do not exist (designated as hallucinations), have false beliefs (designated as delusions) or have an abnormal distrust of others. Negative refers to the lack of behaviors or feelings that are normally present. For example, a person with schizophrenia may become withdrawn and not respond to any emotional stimulus or may have difficulty speaking in a clear and logical manner. People who suffer from this disorder may also feel depressed, anxious, guilty, or tense.

TREVICTA may alleviate symptoms of your illness and reduce the likelihood of them recurring.

Do not use TREVICTA

• if you are allergic to paliperidone or any of the other components of this medication (listed in section 6).
• if you are allergic to other antipsychotic medications, including risperidone.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use TREVICTA.

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

All medications have side effects, and some side effects of this medication may worsen symptoms of other conditions. For this reason, it is essential to discuss the following conditions with your doctor, as they may worsen during treatment with this medication.

• if you have Parkinson's disease
• if you have been diagnosed with a condition whose symptoms include high fever and muscle rigidity (known as Neuroleptic Malignant Syndrome)
• if you have had spasms or uncontrollable movements in your face, tongue, or other parts of your body (tardive dyskinesia)
• if you have had low white blood cell counts (which may have been caused by other medications or not)
• if you are diabetic or have a tendency to develop diabetes
• if you have had breast cancer or a tumor in the pituitary gland (a gland in the brain)
• if you have any heart disease or are receiving treatment for heart conditions that may make you more prone to low blood pressure
• if you have low blood pressure when standing up or feel dizzy
• if you have a history of seizures
• if you have kidney problems
• if you have liver problems
• if you have prolonged and painful erections
• if you have difficulty controlling your body temperature or experience excessive heat
• if you have an abnormally high level of prolactin in your blood or if you have a possible prolactin-dependent tumor
• if you or a family member have a history of blood clots, as antipsychotics have been associated with clot formation.

If you find yourself in any of these situations, talk to your doctor, as it may be necessary to adjust your dose or monitor your condition for some time.

Given that, rarely, a dangerously low count of a certain type of white blood cell responsible for fighting infections in the blood has been observed in patients receiving this medication, your doctor may decide to perform a white blood cell count.

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

This medication may cause you to gain weight. Significant weight gain could be detrimental 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 using this medication, your doctor should monitor for possible signs of hyperglycemia. In patients with pre-existing diabetes mellitus, blood glucose levels should be regularly controlled.

Since this medication can mask the normal response of the body to toxic substances or other diseases, there is a possibility that it may conceal the response to ingested toxins or other diseases.

During eye surgery for cataracts, the pupil (the black circle in the middle of the eye) may not dilate as needed. Additionally, the iris (the colored part of the eye) may become flaccid during surgery and cause eye damage. If you are planning to have eye surgery, be sure to inform your ophthalmologist that you are using this medication.

Children and adolescents

Do not use this medication in children and adolescents under 18 years of age. Its safety and efficacy in these patients are unknown.

Other medications and TREVICTA

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

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

Since this medication primarily acts on the brain, the use of other medications with central action may exacerbate side effects such as drowsiness or other central nervous system effects, such as other psychiatric medications, opioids, antihistamines, and sleep medications.

Since this medication can lower blood pressure, caution should be exercised when combining it with other medications that lower blood pressure.

This medication may reduce the effect of medications used to treat Parkinson's disease and restless leg syndrome (e.g., levodopa).

This medication may cause an electrocardiogram (ECG) anomaly that indicates that electrical impulses take longer to reach a specific part of the heart (known as "prolongation of the QT interval"). Medications that exert this effect include some medications used to regulate heart rhythm or treat infections, as well as other antipsychotics.

If you have a history of seizures, this medication may increase the likelihood of them recurring. Other medications that exert this effect include some medications used to treat depression or infections and other antipsychotics.

TREVICTA should be used with caution with medications that increase central nervous system activity (psychoestimulants such as methylphenidate).

TREVICTA and alcohol

Alcohol should be avoided.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medication. Do not use this medication during pregnancy without discussing it with your doctor first. In newborns of mothers who received paliperidone in the last trimester (the last three months of pregnancy), the following symptoms may appear: tremors, rigidity, or muscle weakness, drowsiness, agitation, respiratory disturbances, and difficulty feeding. If your child exhibits any of these symptoms, seek medical attention for your child.

This medication may pass from the mother to the child through breast milk and be detrimental to the child. For this reason, do not breastfeed while using this medication.

Driving and operating machinery

During treatment with this medication, dizziness, extreme fatigue, and vision problems (see section 4) may occur. These effects should be taken into account in cases where maximum attention is required, such as driving vehicles or operating machinery.

TREVICTA contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free".

This medication is administered by a doctor or healthcare professional. The doctor will inform you when to receive the next injection. It is essential that you do not miss the scheduled dose. If you cannot attend your appointment with the doctor, please make sure to call them immediately to schedule another appointment as soon as possible.

You will receive an injection of TREVICTA in the upper arm or buttock once every 3 months.

Depending on your symptoms, the doctor will increase or decrease the amount of medication administered in the next scheduled injection.

Patients with kidney disorders

If you have a mild kidney disorder, the doctor will determine the appropriate dose of TREVICTA based on the monthly paliperidone palmitate injection dose you have been receiving. If you have a severe or moderate kidney disorder, you should not use this medication.

Advanced age population

If you have reduced renal function, the doctor will determine the appropriate dose of this medication.

If you receive more TREVICTA than you should

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

If a patient receives an excessive amount of paliperidone, they may experience the following symptoms: Drowsiness or sedation, increased heart rate, low blood pressure, electrocardiogram (ECG) abnormalities, or slow and abnormal movements of the face, body, arms, or legs.

If you interrupt treatment with TREVICTA

If you stop receiving the injections, your schizophrenia symptoms may worsen. Do not stop using this medication unless your doctor instructs you to do so.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

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

Inform your doctor immediately if:

•you experience blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the legs), which can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing. If you notice any of these symptoms, seek medical advice immediately.

•you have dementia and observe a sudden change in your mental state or a sudden weakness or numbness of the face, arms, or legs, especially on one side of the body; or if you have difficulty speaking, even for a short time. It may be a sign of a stroke.

•you experience fever, muscle stiffness, sweating, or a reduced level of consciousness (a condition called "Neuroleptic Malignant Syndrome"). You may need immediate medical treatment.

•you are a male and experience prolonged or painful erections. It is known as priapism. You may need immediate medical treatment.

•you experience involuntary rhythmic movements of the tongue, mouth, or face. You may need the withdrawal of paliperidone.

•you experience a severe allergic reaction characterized by fever, swelling of the mouth, face, lips, or tongue, difficulty breathing, itching, skin rash, and sometimes a drop in blood pressure (which constitutes an "anaphylactic reaction"). Even if you have previously tolerated oral risperidone or paliperidone, you may rarely experience allergic reactions after receiving paliperidone injections.

•you are scheduled to undergo eye surgery, ensure that you inform your ophthalmologist that you are receiving this medication. During eye surgery for cataracts, it is possible that the iris (the colored part of the eye) may become flaccid during surgery (known as "flaccid iris syndrome") with subsequent eye damage.

•you experience a dangerously low number of a type of white blood cell necessary to fight blood infections.

The following side effects may occur:

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

• difficulty falling or staying asleep

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

• common cold symptoms, urinary tract infection, feeling of having the flu
• TREVICTA may increase levels of a hormone called "prolactin" that is detected in blood tests (which may or may not cause symptoms). When prolactin symptoms appear, they may include (in men) breast swelling, difficulty getting or maintaining erections, or other sexual dysfunction; (in women) breast discomfort, milk secretion, missed periods, or other menstrual cycle problems.
• high blood sugar, weight gain, weight loss, decreased appetite
• irritability, depression, anxiety
• feeling restless
• parkinsonism: This disease may include slow or altered movement, feeling of stiffness or tension in the muscles (making sudden movements) and sometimes a feeling of "freezing" of movement that is later restarted. Other signs of parkinsonism include walking slowly with dragging feet, trembling while resting, increased saliva and/or drooling, and loss of facial expression.
• feeling drowsy or less attentive
• distonia: This disorder involves involuntary slow or continuous muscle contraction. Although it may affect any part of the body (and may cause abnormal postures), distonia often affects the facial muscles, including abnormal movements of the eyes, mouth, tongue, or jaw.
• dizziness
• discinesia: This disorder involves involuntary muscle movements and may include repetitive, spasmodic, or twisting movements, or spasms
• trembling (agitation)
• headache
• rapid heart rate
• high blood pressure
• cough, nasal congestion
• abdominal pain, vomiting, nausea, constipation, diarrhea, indigestion, toothache
• increased levels of liver enzymes in the blood
• bone or muscle pain, back pain, joint pain

• missed periods, milk secretion
• fever, weakness, fatigue (tiredness)
• reactions at the injection site, with itching, pain, or swelling.

Uncommon side effects (may affect up to 1 in 100 patients)

• bronchitis, pneumonia, respiratory tract infection, sinusitis, urinary tract infection, ear infection, tonsillitis, fungal nail infection, skin infections
• reduction of white blood cells, decrease of a type of white blood cell that helps fight blood infections, reduction of platelets (cells necessary to stop bleeding), anemia
• allergic reaction
• diabetes or worsening of diabetes, increased blood insulin levels (hormone that regulates blood sugar levels)
• increased appetite
• loss of appetite resulting in malnutrition and weight loss
• high triglycerides (a type of fat) in the blood, increased cholesterol in the blood
• sleep disorders, euphoria (mania), decreased libido, nervousness, nightmares
• late discinesia (involuntary movements that cannot be controlled in the face, tongue, or other parts of the body). Inform your doctor immediately if you experience involuntary rhythmic movements of the tongue, mouth, or face. You may need the withdrawal of this medication.

• syncope, urgent desire to move certain parts of the body, dizziness when standing up, attention problems, speech disorders, loss or alteration of taste, decreased skin sensitivity to pain and touch, feeling of pins and needles, numbness, or tingling of the skin
• blurred vision, eye infection, red eyes, dry eyes
• sensation of spinning (vertigo), ringing in the ears, ear pain
• interruption of conduction between the upper and lower parts of the heart, heart conduction disorders, prolonged QT interval of the heart, rapid heart rate when standing up, slow heart rate, abnormal heart rhythm (electrocardiogram or ECG), feeling of palpitations or fluttering in the chest (palpitations)
• low blood pressure, hypotension when standing up (due to this effect, some people treated with this medication may feel weakness or dizziness, or may faint when standing up or sitting suddenly)
• difficulty breathing, respiratory tract congestion, wheezing, throat pain, nasal bleeding
• abdominal discomfort, gastrointestinal or intestinal infection, difficulty swallowing, dry mouth, excessive gas or flatulence
• increased GGT (a liver enzyme called gamma glutamiltransferase) in the blood, increased liver enzymes in the blood
• hives (urticaria), itching, rash, hair loss, eczema, dry skin, skin redness, acne
• increased CPK (creatinfosfoquinase) in the blood, an enzyme that sometimes is released with muscle degradation
• muscle spasms, joint stiffness, muscle weakness, neck pain
• urinary incontinence, frequent urination, painful urination
• erectile dysfunction, sexual function disorders, missed periods or menstrual cycle alterations (in women), breast development in men, sexual dysfunction, breast pain
• swelling of the face, mouth, eyes, or lips, swelling of the body, arms, or legs
• increased body temperature
• changes in gait
• chest pain or discomfort, general feeling of discomfort

• skin hardening
• falls.

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

• eye infection
• skin inflammation caused by mites, abscess under the skin
• increased eosinophils (a type of white blood cell) in the blood
• inappropriate secretion of a hormone that controls urine volume
• presence of sugar in the urine
• complications of uncontrolled diabetes with life-threatening risk
• decreased blood sugar
• excessive water intake
• confusion
• lack of movement or response while awake (catatonia)
• sleepwalking
• absence of emotions
• inability to achieve orgasm
• neuroleptic malignant syndrome (confusion, decreased or lost consciousness, high fever, and severe muscle stiffness), problems in the blood vessels of the brain, including sudden loss of blood flow to the brain (stroke or "mini" stroke), no response to stimuli, loss of consciousness, decreased level of consciousness, seizures (epileptic crises), balance disorder
• abnormal coordination
• glaucoma (increased eye pressure)
• eye movement alterations, "eyes in the back," light sensitivity of the eyes, increased tear production, red eyes
• atrial fibrillation (an alteration of heart rhythm), irregular heartbeats
• blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg). If you experience any of these symptoms, seek medical advice immediately.
• flushing
• difficulty breathing during sleep (sleep apnea)
• pulmonary congestion
• crepitant sounds of the lungs
• pancreatitis, tongue swelling, fecal incontinence, hardened feces
• cracked lips
• skin rash related to the medication, skin thickening, dandruff
• joint swelling
• urinary incontinence
• breast discomfort, breast swelling, breast enlargement
• vaginal discharge
• very low body temperature, chills, feeling of thirst
• withdrawal symptoms from the medication
• accumulation of pus due to infection at the injection site, deep skin infection, abscess at the injection site, hematomas (bruises) at the injection site.

Unknown frequency: cannot be estimated from available data

• dangerously low number of a type of white blood cell necessary to fight infections
• severe allergic reaction characterized by fever, swelling of the mouth, face, lips, or tongue, difficulty breathing, itching, skin rash, and sometimes a drop in blood pressure
• excessive water intake
• eating disorder related to sleep

• diabetes coma
• head shaking
• blood clots in the lungs causing chest pain and difficulty breathing. If you experience any of these symptoms, seek medical advice immediately.
• shallow and agitated breathing, pneumonia caused by aspiration of food, voice changes
• decreased oxygen in parts of the body (due to decreased blood flow)
• intestinal obstruction, lack of intestinal movement causing intestinal obstruction
• yellow skin and eyes (jaundice)
• severe allergic reaction with swelling that can affect the throat and cause difficulty breathing
• skin discoloration, peeling, itching of the scalp or skin
• abnormal posture
• newborns whose mothers took TREVICTA during pregnancy may experience adverse effects from the medication and/or withdrawal symptoms, such as irritability, slow or sustained muscle contractions, tremors, insomnia, respiratory or feeding problems
• prolonged erection (priapism) that may require surgical treatment
• decreased body temperature
• accumulation of dead cells in the skin around the injection site, ulcer at the injection site.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. By doing so, you will help protect the environment.

Composition of TREVICTA

The active ingredient is paliperidone.

Each pre-filled syringe of TREVICTA 175 mg contains 273 mg of palmitate of paliperidone.

Each pre-filled syringe of TREVICTA 263 mg contains 410 mg of palmitate of paliperidone.

Each pre-filled syringe of TREVICTA 350 mg contains 546 mg of palmitate of paliperidone.

Each pre-filled syringe of TREVICTA 525 mg contains 819 mg of palmitate of paliperidone.

The other components are:

Polysorbate 20

Polyethylene glycol 4000

Citric acid monohydrate

Dihydrogen phosphate sodium monohydrate

Sodium hydroxide (for pH adjustment)

Water for injection

Appearance of the product and contents of the package

TREVICTA is a long-acting injectable suspension, white to off-white in color, presented in a pre-filled syringe that the doctor or nurse will shake vigorously to homogenize the suspension before injecting it.

Each package contains 1 pre-filled syringe and 2 needles.

Only some package sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Responsible for manufacturing

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

Reserved for medical professionals

This information is intended only for medical professionals, who must read it together with the complete prescribing information (Summary of Product Characteristics).

For intramuscular injection only. Do notadminister by any other route.

Important

Read the complete instructions before using the product. To ensure proper administration of TREVICTA, it is necessary to read these instructions carefully.

TREVICTA must be administered by a healthcare professional as a single injection.DO NOTsplit the dose into multiple injections.

TREVICTA is indicated for intramuscular injection only. Inject slowly and deeply into the deltoid or gluteal muscle, avoiding injection into a blood vessel.

Dosage

TREVICTA will be administeredonce every 3 months.

Preparation

Remove the label from the syringe and incorporate it into the patient's medical history.

TREVICTA requiresa more vigorous and prolonged agitationthan monthly paliperidone palmitate injection. Shake the syringe vigorously, with the tip pointing upwards, forat least 15 seconds in the 5-minute interval preceding administration(see step 2).

Selection of the safety needle with a thin wall

The safety needles with a thin wall are designed to be used with TREVICTA. It is essential to useonly the needles provided in the TREVICTA package.

Contents of the package per dose

The selection of the needle is determined by the injection site and the patient's weight.

Check the suspension

After shaking the syringe for at least 15 seconds, check the appearance of the suspension in the viewfinder.

The suspension should have a uniform appearance and a white creamy color.

It is normal for small air bubbles to appear.

Open the needle cap and remove the cap

First, open the needle cap by peeling off half of the cover. Place it on a clean surface.

Then, with the syringe pointing upwards, turn the cap clockwise to remove it.

Hold the needle cap

Double the back of the needle cover and the plastic tray. Then, hold the needle cap firmly by the cap, as indicated.

Attach the needle

With the other hand, hold the syringe by the Luer connector and attach the safety needle by rotating it clockwise in the direction of the arrows.

Do not removethe cap until the syringe and needle are perfectly aligned.

Remove the needle cap

Remove the needle cap by pulling it straight out.

Do notrotate the cap, as the needle may come loose from the syringe.

Remove air bubbles

Gently tap the syringe with the tip pointing upwards to allow air bubbles to rise.

Slowly and carefully push the plunger upwards to remove the air.

Inject the dose

Inject the entire contents of the syringeintramuscularly, slowly and deeply into the deltoid or gluteal muscle.

Do not administer by any other route.

Protect the needle

After injection, use your finger or a flat surface to activate the safety mechanism of the needle. The needle will be secure when you hear a "click".

Proper disposal

Dispose of the syringe and needle in an approved container for sharp objects.