INVEGA 9 mg PROLONGED-RELEASE TABLETS

2. What you need to know before taking INVEGA

Do not take INVEGA

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take INVEGA.

• Patient with schizoaffective disorder treated with this medication should be closely monitored for a possible shift from manic to depressive symptoms.
• This medication has not been studied in elderly patients with dementia. However, elderly patients with dementia who are treated with other similar medications may have an increased risk of stroke or death (see section 4, Possible side effects).
• if you have Parkinson's disease or dementia.
• if you have ever been diagnosed with a disease whose symptoms are high fever and muscle stiffness (also known as Neuroleptic Malignant Syndrome).
• if you have ever experienced abnormal movements of the tongue or face (Tardive Dyskinesia).
• You should know that these two disorders can be caused by this type of medication.
• if you have had low white blood cell counts in the past (which may or may not have been caused by other medications)
• if you are diabetic or have a tendency to diabetes.
• if you have heart disease or are being treated for heart diseases that may make you more prone to a decrease in blood pressure.
• if you have epilepsy.
• if you have a swallowing disorder, stomach disorder, or intestinal disorder that reduces your ability to swallow food or digest it with normal intestinal movements.
• if you have diseases associated with diarrhea.
• if you have kidney problems.
• if you have liver problems.
• if you have a prolonged and/or painful erection.
• if you have difficulty controlling your body temperature or are overheated.
• if you have an abnormally high level of the hormone prolactin in your blood or if you have a tumor that is possibly dependent on prolactin.
• if you or someone in your family has a history of blood clots, as antipsychotics are associated with the formation of clots

If you have any of these diseases, please consult your doctor, as it may be necessary to adjust your dose or keep you under observation for a period of time.

Because it has been rarely observed in patients treated with INVEGA that they have a dangerously low number of a type of white blood cells necessary to fight infections in the blood, your doctor may check your white blood cell count.

INVEGA may cause you to gain weight. Significant weight gain can negatively affect your health. Your doctor will regularly monitor your weight.

In patients treated with INVEGA, diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed, and your doctor should check for signs of high blood sugar. In patients with pre-existing diabetes mellitus, blood sugar should be regularly monitored.

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 considering eye surgery, make sure to inform your ophthalmologist that you are using this medication.

Children and adolescents

INVEGA should not be administered to children and adolescents under 15 years of age for the treatment of schizophrenia.

INVEGA should not be administered to children and adolescents under 18 years of age for the treatment of schizoaffective disorder.

This is because it is unknown whether INVEGA is safe or effective in this age group.

Taking INVEGA with other medications

Tell your doctor or pharmacist if you are using or have recently used other medications.

Abnormalities in heart function may appear when taking this medication along with other medications to control heart rhythm or other medications such as antihistamines, antimalarials, or antipsychotics.

Since this medication acts primarily on the brain, it may interfere with other medications (or alcohol) that also act on it, due to the sum of effects on brain function.

This medication may lower blood pressure, so you should be careful if you take this medication with other medications that also lower blood pressure.

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

The effects of this medication may be affected if you take medications that influence the speed of intestinal movement (e.g., metoclopramide).

A reduction in the dose of this medication should be considered when it is administered at the same time as valproate.

The use of oral risperidone with this medication is not recommended, as this combination may cause an increase in side effects.

INVEGA with alcohol

You should avoid consuming alcohol during treatment with this medication.

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 medication.

You should not take this medication during pregnancy unless you have discussed it with your doctor.

The following symptoms may occur in newborn babies of mothers who have been treated with paliperidone in the last trimester of pregnancy (last three months of pregnancy): tremors, stiffness and/or muscle weakness, drowsiness, agitation, breathing problems, and difficulty feeding. If your baby develops any of these symptoms, you should contact your doctor.

You should not take this medication during breastfeeding.

Driving and using machines

During treatment with this medication, dizziness and vision problems (see section 4, Possible side effects) may occur. This should be taken into account when maximum attention is required, for example, when driving or operating machinery.

The 3 mg INVEGA tablet contains lactose

The 3 mg tablet of this medication contains lactose, a type of sugar. If your doctor has told you that you do not tolerate some sugars, talk to them before taking this medication.

INVEGA contains sodium

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

3. How to take INVEGA

Follow the instructions for administration of this medication exactly as indicated by your doctor, pharmacist, or nurse.

Use in adults

The recommended dose in adults is 6 mg once daily in the morning. Your doctor may increase or decrease it within the dosage range of 3 mg to 12 mg once daily in case of schizophrenia or 6 mg to 12 mg once daily in case of schizoaffective disorder. This depends on how well the medication works for you.

Use in adolescents

The recommended starting dose for the treatment of schizophrenia in adolescents aged 15 years and older is 3 mg once daily taken in the morning.

For adolescents who weigh 51 kg or more, the dose may be increased within the range of 6 mg to 12 mg once daily.

For adolescents who weigh less than 51 kg, the dose may be increased to 6 mg once daily.

Your doctor will decide how much you should take. The amount you take depends on how well the medication works for you.

How and when to take INVEGA

This medication should be taken by mouth, swallowed whole with water or other liquids. It should not be chewed, broken, or crushed.

This medication should be taken in the morning with breakfast or on an empty stomach, but in the same way every day. Do not alternate between taking the medication one day with breakfast and the next day on an empty stomach.

The active substance, paliperidone, is dissolved once swallowed, and the tablet coating is eliminated from the body through the feces.

Patients with kidney problems

Your doctor may adjust your dose of this medication according to your kidney function.

Elderly

Your doctor may reduce your dose of medication if your kidney function is reduced.

If you take more INVEGA than you should

Contact your doctor immediately. You may experience drowsiness, fatigue, abnormal body movements, problems standing and walking, dizziness due to low blood pressure, and changes in heartbeats.

If you forget to take INVEGA

Do not take a double dose to make up for forgotten doses. If you forget a dose, take the next dose the following day. If you forget two or more doses, contact your doctor.

If you stop taking INVEGA

Do not stop taking this medication, as you will lose its effects. You should not stop taking this medication unless your doctor tells you to, as your symptoms may come back.

If you have any further questions about the use of this medication, ask your doctor, pharmacist, or nurse.

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 include swelling, pain, and redness of the leg), which can circulate 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 experience a sudden change in your mental state or sudden weakness or numbness of the face, arms, or legs, especially on one side, or have difficulty speaking even for a short period. These may be signs of a stroke
• you have fever, muscle stiffness, sweating, or a decrease in the level of consciousness (a condition known as "Neuroleptic Malignant Syndrome"). You may need immediate medical treatment
• you are a man and experience a prolonged or painful erection. It is known as priapism. You may need immediate medical treatment
• you experience involuntary rhythmic movements of the tongue, mouth, or face. It may be necessary to withdraw paliperidone
• you have 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 (i.e., an "anaphylactic reaction").

Very common: may affect more than 1 in 10 patients

• difficulty staying or falling asleep
• parkinsonism: This disease may include slow or altered movement, feeling of stiffness or muscle tension (making jerky movements) and sometimes a feeling of "freezing" of movement that then restarts. Other signs of parkinsonism include walking slowly, dragging feet, tremors while resting, increased saliva and/or drooling, and loss of facial expressiveness.
• restlessness
• feeling drowsy or less attentive
• headache.

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

• chest infection (bronchitis), symptoms of a common cold, nose infection, urinary tract infection, feeling like you have the flu
• weight gain, increased appetite, weight loss, decreased appetite, euphoria (mania), irritability, depression, anxiety
• distonia: It is a disease 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 disease involves involuntary muscle movements and may include repetitive, spasmodic, or twisting movements, or spasms
• tremors (agitation)
• blurred vision
• disruption of conduction between the upper and lower parts of the heart, anomalies in the electrical conduction of the heart, prolongation of the QT interval in the heart, slow heartbeat, rapid heartbeat
• decrease in blood pressure when standing up (as a consequence, some people taking INVEGA may feel weakness, dizziness, or loss of consciousness when getting up or sitting down suddenly), increased blood pressure
• sore throat, cough, nasal congestion
• abdominal pain or discomfort, vomiting, nausea, constipation, diarrhea, indigestion, dry mouth, toothache
• increase in liver transaminases in the blood
• itching, skin rash
• bone or muscle pain, back pain, joint pain
• loss of menstrual periods
• fever, weakness, fatigue (tiredness).

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

• pneumonia, respiratory tract infection, bladder infection, ear infection, tonsillitis
• decrease in the number of white blood cells in the blood, decrease in platelets (blood cells that help stop bleeding), anemia, decrease in the number of red blood cells in the blood
• INVEGA may increase the levels of a hormone called "prolactin" that is detected in blood tests (which may or may not cause symptoms). 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 cycle problems.
• diabetes or worsening of diabetes, increased blood sugar, increased waist circumference, loss of appetite that causes malnutrition and weight loss, increased triglycerides in the blood (a type of fat)
• sleep disorder, confusion, decreased sexual desire, inability to achieve orgasm, nervousness, nightmares
• tardive dyskinesia (involuntary, uncontrollable 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 INVEGA.
• seizures (epileptic fits), fainting, restlessness that causes movement of parts of the body, dizziness when standing up, attention disorder, speech problems, loss or alteration of taste, decreased sensitivity of the skin to pain or touch, tingling, prickling, or numbness of the skin
• eye hypersensitivity to light, eye infection or "red eye", dry eyes
• feeling that everything is spinning (vertigo), ringing in the ears, ear pain
• irregular heartbeat, anomaly in the electrical activity of the heart (electrocardiogram or ECG), feeling of fluttering or pounding in the chest (palpitations)
• decrease in blood pressure
• shortness of breath, wheezing, nosebleeds
• swelling of the tongue, stomach or intestinal infection, difficulty swallowing, excess gas or flatulence, increase in GGT (a liver enzyme called gamma-glutamyltransferase) in blood, increase in liver enzymes in blood
• hives (or "urticaria"), hair loss, eczema, acne
• increase in CPK (creatine phosphokinase) in blood, an enzyme that is sometimes released with muscle breakdown, muscle spasms, joint stiffness, joint swelling, muscle weakness, neck pain
• urinary incontinence (loss of bladder control), frequent urination, inability to urinate, painful urination
• erectile dysfunction, ejaculation disorder
• loss of menstrual periods or other cycle problems (women), milk secretion from the breasts, sexual dysfunction, breast pain, breast discomfort
• swelling of the face, mouth, eyes, or lips, swelling of the body, arms, or legs
• chills, increased body temperature
• change in gait
• feeling of thirst
• chest pain, chest discomfort, feeling of discomfort
• falls.

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

• eye infection, fungal infection of the nails, skin infection, skin inflammation caused by mites
• dangerously low number of a type of white blood cells in the blood necessary to fight infections
• decrease in a type of white blood cells in the blood that help fight infections, increase in eosinophils (a type of white blood cell) in the blood
• 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, allergic reaction
• sugar in the urine
• inappropriate secretion of a hormone that controls urine volume
• complications of uncontrolled diabetes with life-threatening potential
• excessive water intake, decreased blood sugar, excessive water intake, increased cholesterol in the blood
• sleepwalking
• apathy
• neuroleptic malignant syndrome (confusion, decreased or lost consciousness, high fever, and severe muscle stiffness)
• loss of consciousness, balance disorder, abnormal coordination
• problems in the blood vessels of the brain, coma due to uncontrolled diabetes, unresponsive to stimuli, decreased level of consciousness, head agitation
• glaucoma (increased eye pressure), increased tearing, redness of the eyes, problems with eye movement, eye rotation
• atrial fibrillation (abnormal heart rhythm), rapid heartbeat when standing up
• blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg), which can circulate through the blood vessels to the lungs, causing chest pain and difficulty breathing. If you experience any of these symptoms, seek medical help immediately.
• decrease in oxygen in parts of the body (due to decreased blood flow), flushing
• breathing problems during sleep (sleep apnea), rapid, shallow breathing
• pneumonia caused by aspiration of food, congestion of the airways, voice disorder
• intestinal obstruction, fecal incontinence, very hard stools, absence of intestinal movement that causes obstruction
• yellowing of the skin and eyes (jaundice)
• pancreatitis
• severe allergic reaction with swelling that can affect the throat, causing difficulty breathing
• thickening of the skin, dry skin, redness of the skin, skin discoloration, scaly, itchy skin or scalp, dandruff
• muscle fiber breakdown and muscle pain (rhabdomyolysis), abnormal posture
• priapism (a prolonged erection that may require surgical treatment)
• breast development in men, breast enlargement, milk secretion from the breasts, vaginal discharge
• delayed menstrual periods, breast enlargement
• very low body temperature, decreased body temperature
• withdrawal symptoms from the medication.

Unknown frequency: cannot be estimated from the available data

• lung congestion
• increased insulin (a hormone that controls blood sugar levels) in the blood.

The following adverse effects have appeared with the use of another medicine called risperidone, which is very similar to paliperidone, so it is also expected to appear with INVEGA: sleep-related eating disorder, other types of cerebrovascular problems, and crackling sounds in the lungs. Eye problems may also appear during cataract surgery. During cataract surgery, a condition called intraoperative floppy iris syndrome (IFIS) may occur if you are taking or have taken INVEGA. If you need to undergo cataract surgery, make sure to inform your ophthalmologist if you are taking or have taken this medication.

Additional adverse effects in adolescents

Adolescents generally presented similar adverse effects to those found in adults, except for the following adverse effects that were detected more frequently:

• feeling drowsy or less attentive
• parkinsonism: This disease may include slow or altered movement, feeling of stiffness or muscle tension (making jerky movements) and sometimes a feeling of "freezing" of movement that then restarts. Other signs of parkinsonism include walking slowly, dragging feet, tremors while resting, increased saliva and/or drooling, and loss of facial expressiveness.
• weight gain
• common cold symptoms
• restlessness
• tremors (agitation)
• stomach pain
• milk secretion from the breasts in girls
• breast swelling in boys
• acne
• speech problems
• stomach or intestinal infection
• nasal bleeding
• ear infection
• high triglycerides in the blood (a type of fat)
• feeling of movement (vertigo).

Reporting of adverse effects

If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects that do not appear in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of INVEGA

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

Do not use this medicine after the expiration date that appears on the blister/pack and on the carton after EXP. The expiration date is the last day of the month indicated.

Bottles: Do not store above 30°C. Keep the bottle tightly closed to protect it from moisture.

Blister packs: Do not store above 30°C. Store in the original packaging to protect it from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of INVEGA

The active ingredient is paliperidone.

Each 3 mg prolonged-release tablet of INVEGA contains 3 mg of paliperidone.

Each 6 mg prolonged-release tablet of INVEGA contains 6 mg of paliperidone.

Each 9 mg prolonged-release tablet of INVEGA contains 9 mg of paliperidone.

Each 12 mg prolonged-release tablet of INVEGA contains 12 mg of paliperidone.

The other ingredients are:

Coated tablet core:

Polyethylene oxide 200K

Sodium chloride Povidone (K29-32)

Stearic acid

Butylhydroxytoluene (E321)

Ferric oxide (Yellow) (E172) (only 3 and 12 mg tablets)

Polyethylene oxide 7000K

Ferric oxide (Red) (E172)

Hydroxyethyl cellulose

Polyethylene glycol 3350

Cellulose acetate

Iron oxide (Black) (E172) (only 9 mg tablets)

Colored coating:

Hypromellose

Titanium dioxide (E171)

Polyethylene glycol 400 (only 6, 9, and 12 mg tablets)

Ferric oxide (Yellow) (E172) (only 6 and 12 mg tablets)

Ferric oxide (Red) (E172) (only 6 and 9 mg tablets)

Lactose monohydrate (only 3 mg tablets)

Triacetin (only 3 mg tablets)

Carnauba wax

Printing ink:

Iron oxide (Black) (E172)

Propylene glycol

Hypromellose

Product Appearance and Package Contents

The INVEGA prolonged-release tablets are capsule-shaped. The 3 mg tablets are white and engraved with “PAL 3”, the 6 mg tablets are beige and engraved with “PAL 6”, the 9 mg tablets are pink and engraved with “PAL 9”, and the 12 mg tablets are dark yellow and engraved with “PAL12”. All tablets are marketed in the following presentations:

• Bottles: The tablets are provided in a plastic bottle with a child-resistant closure. Each bottle contains 30 tablets or 350 tablets. Each bottle contains two silica gel bags to protect the tablets from moisture and keep them dry.
• Blister packs: The tablets are provided in blister packs packaged in boxes of 14, 28, 30, 49, 56, and 98 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen-Cilag SpA Via C. Janssen

04100 Borgo San Michele

Latina

Italy

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

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