TREVICTA 350 MG PROLONGED-RELEASE INJECTABLE SUSPENSION

2. What you need to know before you use TREVICTA

Do not use TREVICTA

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using TREVICTA.

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

All medicines can cause side effects and some of the side effects of this medicine may worsen the symptoms of other illnesses. For this reason, it is important that you discuss with your doctor any of the following illnesses that may worsen during treatment with this medicine.

• if you have Parkinson's disease
• if you have been diagnosed with a disease whose symptoms include high temperature and muscle stiffness (known as Neuroleptic Malignant Syndrome)
• if you have had spasms or uncontrolled movements of the face, tongue, or other parts of the body (tardive dyskinesia)
• if you have had low white blood cell counts (which may have been caused by other medicines or not)
• if you are diabetic or have a tendency to 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 diseases that may make you more prone to low blood pressure
• if you have low blood pressure when you stand up or sit up suddenly
• if you have a history of seizures
• if you have kidney problems
• if you have liver problems
• if you have a prolonged and/or painful erection
• if you have difficulty controlling body temperature or excessive overheating
• if you have an abnormally high blood level of the hormone prolactin 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 the formation of clots.

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

Given that it has been rarely observed that patients receiving this medicine have a dangerously low number of a certain type of white blood cell responsible for fighting infections in the blood, the doctor may decide to perform white blood cell counts.

Even if you have previously tolerated oral paliperidone or risperidone, rare allergic reactions may occur after receiving TREVICTA injections. Seek medical help immediately 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 medicine may cause weight gain. Significant weight gain could be harmful to your health. Your doctor will regularly check your body weight.

Since diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed in some patients using this medicine, the doctor should monitor for possible signs of high blood sugar. In patients with pre-existing diabetes mellitus, blood sugar levels should be regularly checked.

Since this medicine can reduce the vomiting reflex, there is a possibility that it may mask the normal response of the body to the ingestion of toxic substances or other illnesses.

During eye surgery for cataracts, the pupil (the black circle in the center of the eye) may not increase in size as needed. Additionally, the iris (the colored part of the eye) may become flaccid during surgery, which can cause eye damage. If you are planning to have eye surgery, make sure to inform your ophthalmologist that you are using this medicine.

Children and adolescents

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

Other medicines and TREVICTA

Tell your doctor if you are taking, have recently taken, or might 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 on the brain, the use of other medicines with brain action may exaggerate side effects such as drowsiness or other brain effects, such as other psychiatric medicines, opioids, antihistamines, and sleeping medicines.

Because this medicine can lower blood pressure, caution should be exercised 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) that indicates that the electrical impulses take longer to reach a specific part of the heart (known as "prolongation of the QT interval"). Among the medicines that have this effect are some 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 that have this effect include some medicines used to treat depression or infections and other antipsychotics.

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

TREVICTA with alcohol

Alcohol should be avoided.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. You should not use this medicine during pregnancy unless you have discussed it with your doctor. In newborn babies of mothers who have received paliperidone in the last trimester (the last three months of pregnancy), the following symptoms may appear: tremors, stiffness or muscle weakness, drowsiness, agitation, breathing problems, or difficulty feeding. If your child shows any of these symptoms, seek medical attention for your child.

This medicine can pass from mother to child through breast milk and be harmful to the child. For this reason, you should not breastfeed while using this medicine.

Driving and using machines

During treatment with this medicine, 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, for example, when driving vehicles or operating machinery.

TREVICTA contains sodium

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

3. How to use TREVICTA

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

You will be given a TREVICTA injection in the upper arm or buttock once every 3 months.

Depending on your symptoms, the doctor will increase or decrease the amount of medicine you will receive in the next scheduled injection.

Patients with kidney disorders

If you have mild kidney problems, the doctor will determine the appropriate dose of TREVICTA based on the dose of paliperidone palmitate injectable suspension you have been receiving. If you have moderate or severe kidney problems, you should not use this medicine.

Elderly population

If you have reduced kidney function, the doctor will determine the appropriate dose of this medicine.

If you receive more TREVICTA than you should

This medicine 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, changes in the electrocardiogram (heart electrical recording), or slow and abnormal movements of the face, body, arms, or legs.

If you stop using TREVICTA

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Report immediately to your doctor if:

• you have blood clots in the veins, especially in the legs (symptoms are swelling, pain, and redness of the legs), which can reach the lungs through the bloodstream, 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 sudden weakness or numbness of the face, arms, or legs, especially on one side of the body; or if you have difficulty speaking, even if it's for a short time. It could be a sign of a stroke.
• you have fever, muscle stiffness, sweating, or reduced consciousness (a disorder called "Neuroleptic Malignant Syndrome"). You may need immediate medical treatment.
• you are male and have prolonged or painful erections. This is called priapism. You may need immediate medical treatment.
• you have involuntary rhythmic movements of the tongue, mouth, and face. It may be necessary to withdraw paliperidone.
• you suffer 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 suffer from allergic reactions after receiving paliperidone injections.
• you are scheduled to undergo eye surgery, make sure to tell your ophthalmologist that you are taking this medicine. During eye surgery for cataracts, it is possible that the iris (the colored part of the eye) becomes flaccid during surgery (known as "floppy iris syndrome") with consequent eye damage.
• you have a dangerously low number of a type of white blood cell necessary to fight blood infections.

The following adverse effects may appear:

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

• difficulty falling asleep or staying asleep

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

• common cold symptoms, urinary tract infection, feeling of having the flu
• TREVICTA may increase the levels of a hormone called "prolactin" that is detected in blood tests (which may cause symptoms or not). When symptoms of increased prolactin appear, they may include (in men) breast swelling, difficulty having or maintaining erections, or other sexual dysfunctions; (in women) breast discomfort, milk secretion from the breasts, loss of menstrual periods, or other problems with the menstrual cycle.
• high blood sugar, weight gain, weight loss, decreased appetite
• irritability, depression, anxiety
• feeling of restlessness
• 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 then restarts. Other signs of parkinsonism include walking slowly while dragging the feet, tremors while at rest, increased saliva and/or drooling, and loss of facial expressiveness.
• restlessness, feeling drowsy or less attentive
• distonia: It is a disorder that involves slow or continuous involuntary contraction of the muscles. Although any part of the body can be affected (and can cause abnormal postures), distonia often affects the muscles of the face, including abnormal movements of the eyes, mouth, tongue, or jaw.
• dizziness
• dykinesia: This disorder involves involuntary muscle movements and may include repetitive, spasmodic, or twisting movements, or spasms
• tremors (shakiness)
• headache
• rapid heart rate
• high blood pressure
• cough, nasal congestion
• abdominal pain, vomiting, nausea, constipation, diarrhea, indigestion, toothache
• increased liver transaminases in the blood
• bone or muscle pain, back pain, joint pain

• loss of menstrual periods, milk secretion from the breasts
• fever, weakness, fatigue (tiredness)
• reactions at the injection site, with itching, pain, or swelling.

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

• pneumonia, chest infection (bronchitis), respiratory tract infection, sinusitis, bladder infection, ear infection, tonsillitis, fungal infection of the nails, skin infections
• reduction of white blood cell count, decrease in a type of white blood cell that helps fight 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 in the blood, high cholesterol in the blood
• sleep disorders, euphoria (mania), decreased sexual desire, nervousness, nightmares
• late dykinesia (spasms or uncontrolled spasmodic movements of the face, tongue, or other parts of the body). Report to your doctor immediately if you experience involuntary rhythmic movements of the tongue, mouth, or face. It may be necessary to withdraw this medicine.

• fainting, overwhelming urge 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, sensation of tingling, pinching, or numbness of the skin
• blurred vision, eye infection, or red eyes, dry eyes
• feeling that everything is spinning (vertigo), ringing in the ears, ear pain
• disruption of conduction between the upper and lower parts of the heart, cardiac conduction disorders, prolongation of the QT interval of the heart, accelerated heart rate when standing up, slowed heart rate, anomalies in the heart's electrical recording (electrocardiogram or ECG), sensation of palpitations or fluttering in the chest (palpitations)
• low blood pressure, low blood pressure when standing up (due to this effect, some people treated with this medicine may feel weakness or dizziness, or may faint when getting up or sitting down suddenly)
• difficulty breathing, congestion of the airways, wheezing, sore throat, nasal bleeding
• abdominal discomfort, gastric or intestinal infection, difficulty swallowing, dry mouth, excessive gas or flatulence
• increased GGT (a liver enzyme called gamma-glutamyltransferase) in the blood, increased liver enzymes in the blood
• appearance of hives (or urticaria), itching, rash, hair loss, eczema, dry skin, redness of the skin, acne
• increased CPK (creatine phosphokinase) in the blood, an enzyme that is sometimes released with muscle breakdown
• muscle spasms, joint stiffness, muscle weakness, neck pain
• urinary incontinence (loss of bladder control), frequent urination, pain when urinating
• erectile dysfunction, ejaculation disorders, loss of menstrual periods or alterations of the cycle (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, feeling of general malaise

• skin hardening
• falls.

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

• eye infection
• skin inflammation caused by mites, abscess under the skin
• increase in 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 risks
• low blood sugar
• excessive water intake
• confusion
• lack of movement or response while being awake (catatonia)
• sleepwalking
• absence of emotions
• inability to reach 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), unresponsiveness, loss of consciousness, decreased level of consciousness, seizures (epileptic fits), balance disorder
• abnormal coordination
• glaucoma (increased internal eye pressure)
• eye movement disorders, "glassy eyes", hypersensitivity of the eyes to light, increased tearing, redness of the eyes
• atrial fibrillation (a heart rhythm disorder), 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 help immediately.
• flushing
• difficulty breathing during sleep (sleep apnea)
• pulmonary congestion
• crackling sounds in the lungs
• pancreatitis, tongue swelling, fecal incontinence, passing very hard stools
• chapped lips
• drug-related skin rash, skin thickening, dandruff
• joint swelling
• inability to urinate
• breast discomfort, breast swelling, increased breast size
• vaginal discharge
• very low body temperature, chills, feeling of thirst
• withdrawal symptoms from the medicine
• pus accumulation due to infection at the injection site, infection of the deep layers of the skin, cyst at the injection site, hematoma (bruising) at the injection site.

Frequency not known: cannot be estimated from the 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 and dangerous water intake
• sleep-related eating disorder

• diabetic coma
• head shaking
• blood clots in the lungs causing chest pain and difficulty breathing. If you experience any of these symptoms, seek medical help immediately.
• shallow and agitated breathing, pneumonia caused by aspiration of food, voice changes
• decrease in oxygen in parts of the body (due to decreased blood flow)
• intestinal obstruction, lack of intestinal movement that causes an intestinal obstruction
• yellowing of the 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 mother has taken TREVICTA during pregnancy may experience adverse effects from the medicine and/or withdrawal symptoms, such as irritability, slow or sustained muscle contractions, tremors, insomnia, respiratory or feeding problems
• priapism (a prolonged erection that may require surgical treatment)
• decreased body temperature
• accumulation of dead cells in the skin surrounding the injection site, ulcer at the injection site.

Reporting of side effects

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

5. Storage of TREVICTA

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

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

This medicine does not require special storage conditions.

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

6. Container Contents and Additional Information

TREVICTA Composition

The active ingredient is paliperidone.

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

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

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

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

The other components are:

Polysorbate 20

Polyethylene glycol 4000

Citric acid monohydrate

Sodium dihydrogen phosphate monohydrate

Sodium hydroxide (for pH adjustment)

Water for injectable preparations

Product Appearance and Container Contents

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 container contains 1 pre-filled syringe and 2 needles.

Only certain package sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Information Reserved for Healthcare Professionals

This information is intended solely for healthcare professionals, who should read it in conjunction 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 carefully read these instructions for use.

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

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

Dosage

TREVICTA will be administered once every 3 months.

Preparation

Remove the label from the syringe and attach it to the patient's medical record.

TREVICTA requires more vigorous and prolonged shakingthan the monthly paliperidone palmitate injectable. Shake the syringe vigorously, with the tip pointing upwards, for at least 15 seconds in the 5-minute interval preceding administration(see step 2).

Selection of the Thin-Walled Safety Needle

Thin-walled safety needles are designed for use with TREVICTA. It is essential to use only the needles provided in the TREVICTA package.

Package Contents 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 viewing window.

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

It is normal for small air bubbles to appear.

Open the Needle Blister Pack and Remove the Cap.

First, open the needle blister pack by peeling back the cover to the middle. Place it on a clean surface.

Then, with the syringe facing upwards, twist the rubber cap to remove it.

Hold the Needle Blister Pack.

Bend back the foil that covers the needle and the plastic tray. Then, firmly grasp the needle sheath, holding it by the blister pack as indicated.

Attach the Needle

With the other hand, hold the syringe by the luer connection and attach the safety needle with a gentle clockwise twist.

Do not removethe blister pack until the syringe and needle are perfectly engaged.

Remove the Needle Cap

Remove the needle cap by pulling it straight off.

Do nottwist the cap, as this may loosen the needle from the syringe.

Eliminate Air Bubbles

Tap the syringe gently with the tip pointing upwards to make any air bubbles rise.

Slowly and carefully, press the plunger upwards to expel the air.

Inject the Dose

Slowly inject the entire contents of the syringeintramuscularly, deeply into the deltoid or gluteus.

Do not administer by any other route.

Protect the Needle

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

Proper Disposal

Discard the unused syringe and needle in an approved sharps container.