Product Information for the User

Xeplion 25 mg Long-Acting Injectable Suspension

Xeplion 50 mg Long-Acting Injectable Suspension

Xeplion 75 mg Long-Acting Injectable Suspension

Xeplion 100 mg Long-Acting Injectable Suspension

Xeplion 150 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.

• Consult your doctor, pharmacist, or nurse if you have any questions.
• Consult your doctor, pharmacist, or nurse if you experience any adverse effects, even if they are not listed in this product information. See section 4.

1. How to use Xeplion
2. Adverse effects
3. Storage of Xeplion

1. Contents of the package and additional information

Xeplion contains the active ingredient paliperidone, which belongs to the class of antipsychotic medications and is used as a maintenance treatment for the symptoms of schizophrenia in adult patients who are stabilized with paliperidone or risperidone.

If you have shown a response to paliperidone or risperidone in the past and have mild or moderate symptoms, your doctor may initiate treatment with Xeplion without prior stabilization with paliperidone or risperidone.

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 (known as hallucinations), have false beliefs (known 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 withdraw into themselves and not respond to any emotional stimuli 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.

Xeplion may help alleviate the symptoms of your illness and prevent them from recurring.

Do not use Xeplion

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

Warnings and precautions

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

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

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 to discuss with your doctor any of the following diseases, which may worsen during treatment with this medicine:

• if you have Parkinson's disease
• if you have ever been diagnosed with a disease whose symptoms include high temperature and muscle rigidity (also known as Neuroleptic Malignant Syndrome)

• if you have ever experienced abnormal movements of the tongue or face (Tardive Dyskinesia)
• if you have had low white blood cell counts in the past (which may or may not have been caused by other medicines)
• if you are diabetic or have a tendency to develop diabetes
• if you have had breast cancer or a tumor in the pituitary gland of the brain

• if you have any heart disease or if you are receiving treatment for heart diseases that may make you more prone to a drop in blood pressure
• if you have low blood pressure when standing up or getting up quickly
• if you have epilepsy
• if you have kidney problems

• if you have liver problems
• if you have a prolonged and painful erection

• if you have difficulty controlling your body temperature or are hot
• if you have an abnormally high level of prolactin in your blood or if you have a tumor that may be dependent on prolactin
• if you or a family member has a history of blood clots, as antipsychotics have been associated with the formation of blood 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 time.

Because in very rare cases, a dangerously low number of a type of white blood cell necessary to fight infections in the blood has been observed in patients treated with this medicine, your doctor may check your white blood cell count.

Even if you have previously tolerated oral paliperidone or risperidone, rare allergic reactions may occur after receiving Xeplion 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 medicine 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 this medicine, diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed. Your doctor should check for signs of increased blood sugar. In patients with pre-existing diabetes mellitus, blood sugar should be regularly monitored.

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

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 this may cause eye damage. If you are planning to have eye surgery, be sure to inform your ophthalmologist that you are using this medicine.

Children and adolescents

Do not use this medicine in children under 18 years.

Use of Xeplion with other medicines

Inform your doctor if you are using, have used recently or may need to use any other medicine.

The use of this medicine with carbamazepine (an antiepileptic and mood stabilizer) may require a change in your dose of this medicine.

Since this medicine primarily acts on the brain, interaction with other medicines that also act on it may cause an exaggeration of side effects, such as drowsiness or other effects on the brain, such as other psychiatric medicines, opioids, antihistamines and sleep medicines.

Since this medicine may reduce blood pressure, you should be careful if you use this medicine with other medicines that also reduce blood pressure.

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

This medicine may cause an anomaly in the electrocardiogram (ECG) that shows that a prolonged period is needed for an electrical impulse to travel through a certain part of the heart (known as "prolongation of the QT interval"). Other medicines that have this effect include some medicines used to treat heart rhythm or to treat infections, as well as other antipsychotics.

If you are prone to seizures, this medicine may increase your chances of experiencing them. Other medicines that have this effect include some medicines used to treat depression or to treat infections, as well as other antipsychotics.

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

Xeplion with alcohol

Alcohol should be avoided.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine. Do not use this medicine 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 three months of pregnancy (last trimester of pregnancy): tremor, rigidity and/or muscle weakness, drowsiness, agitation, breathing problems and difficulty feeding. If your baby develops any of these symptoms, contact your doctor.

This medicine may pass from mother to baby through breast milk and may harm the baby. Therefore, do not breastfeed while using this medicine.

Driving and operating machinery

During treatment with this medicine, dizziness, extreme fatigue and vision problems (see section 4) may occur. This should be taken into account when requiring maximum attention, for example, when driving or operating machinery.

Xeplion contains sodium

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

Your doctor or another healthcare professional will administer this medication. Your doctor will tell you when to receive the next injection. It is essential that you do not miss any scheduled doses. If you cannot attend your appointment with your doctor, make sure to call them immediately to schedule another appointment as soon as possible.

You will receive the first injection (150 mg) and the second injection (100 mg) of this medication in the upper arm approximately one week apart. From then on, you will receive an injection (between 25 mg and 150 mg) in the upper arm or buttocks once a month.

If your doctor is switching you from long-acting risperidone injectable to this medication, you will receive the first injection of this medication (between 25 mg and 150 mg) in the upper arm or buttocks at the next scheduled injection. From then on, you will receive an injection (between 25 mg and 150 mg) in the upper arm or buttocks once a month.

Your doctor may increase or decrease the amount of medication you receive at the time of the monthly scheduled injection based on your symptoms.

Patients with kidney problems

Your doctor may adjust the dose of this medication according to your renal function. If you have mild kidney problems, your doctor may give you a lower dose. You should not use this medication if you have moderate or severe kidney problems.

Patients with advanced age

Your doctor may reduce the dose of this medication if your kidney function is decreased.

If you receive more Xeplion than you should

You will receive this medication under medical supervision, so it is unlikely that you will receive an excessive dose.

Patients who have received an excessive amount of paliperidone may experience the following symptoms: drowsiness or sedation, rapid heart rate, low blood pressure, electrocardiogram abnormalities (heart tracing), or slow or abnormal movements of the face, body, arms, or legs.

If you stop treatment with Xeplion

If you stop receiving your injections, the effects of the medication will be lost. Do not stop using this medication unless your doctor tells you to, as your symptoms may return.

If you have any other questions about using this medication, 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 leg), 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 experience a sudden change in your mental state or sudden weakness or numbness in the face, arms, or legs, especially on one side, or it is difficult for you to speak even for a short period of time. These may be signs of a stroke.

• You experience fever, muscle stiffness, sweating, or a decrease in 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. This is known as priapism. You may need immediate medical treatment.
• You experience involuntary rhythmic movements of the tongue, mouth, and 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, rash, and sometimes a decrease in blood pressure (i.e., an "anaphylactic reaction"). Even if you have previously tolerated oral risperidone or paliperidone, in rare cases, allergic reactions have occurred after receiving paliperidone injections.

• You are scheduled to undergo eye surgery, ensure that you 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) will be flaccid during surgery (known as "flaccid iris syndrome") which can cause 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: can affect more than 1 in 10 patients

• Difficulty staying or falling asleep.

Common side effects: can affect up to 1 in 10 patients

• Common cold symptoms, urinary tract infection, feeling like having the flu
• Xeplion 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, loss of menstrual periods, or other cycle problems.

• Increased blood sugar, weight gain, weight loss, decreased appetite
• Irritability, depression, anxiety
• Parkinsonism: This disease may include slow or altered movement, sensation of stiffness or tension in the muscles (making sudden movements) and sometimes a sensation of "freezing" of movement that is then restarted. Other signs of parkinsonism include walking slowly dragging the feet, trembling while resting, increased saliva and/or drooling, and loss of facial expression
• Restlessness, feeling drowsy or less attentive
• Dystonia: This disorder involves involuntary slow or continuous muscle contraction. Although it can affect any part of the body (and may cause abnormal postures), dystonia often affects the facial muscles, including abnormal movements of the eyes, mouth, tongue, or jaw

• Dizziness
• Dyskinesia: This disorder involves involuntary muscle movements and may include repetitive, spasmodic, or writhing movements, or spasms

• Tremor (agitation)
• Headache
• Fast heart rate
• Increased blood pressure
• Cough, nasal congestion
• Abdominal pain, vomiting, nausea, constipation, diarrhea, indigestion, toothache
• Increased liver enzymes in blood
• Muscle or bone pain, back pain, joint pain
• Loss of menstrual periods
• Milk secretion from the breasts
• Fever, weakness, fatigue (tiredness)
• A reaction at the injection site, including itching, pain, or swelling.

Uncommon side effects: can affect up to 1 in 100 patients

• Pneumonia, chest infection (bronchitis), respiratory tract infection, nasal infection, urinary tract infection, ear infection, fungal nail infection, tonsillitis, skin infection
• Decreased white blood cell count, decreased type of white blood cell count that helps fight blood infections, decreased platelet count (a type of blood cell that helps stop bleeding), anemia
• Allergic reaction
• Diabetes or worsening of diabetes, increased insulin (a hormone that controls blood sugar levels) in blood
• Increased appetite
• Loss of appetite leading to malnutrition and weight loss
• Increased triglycerides in blood (fat), increased cholesterol in blood
• Sleep disorder, euphoria (mania), decreased sex drive, nervousness, nightmares
• Tardive dyskinesia (involuntary, uncontrollable 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 to withdraw from this medicine.

• Loss of consciousness, restlessness causing movement of body parts, dizziness when standing up, altered attention, speech problems, loss or alteration of taste, decreased skin sensitivity to pain or touch, sensation of pins and needles, numbness, or tingling of the skin

• Blurred vision, eye infection, or "red eye," dry eyes
• Sensation of spinning (vertigo), ringing in the ears, ear pain
• Abnormal heart rhythm, abnormal heart activity, prolonged QT interval in the heart, fast heart rate when standing up, slow heart rate, abnormal heart tracing (electrocardiogram or ECG), sensation of fluttering or pounding in the chest (palpitations)

• Decreased blood pressure, low blood pressure when standing up (therefore, some people taking this medicine may feel weak, dizzy, or faint when standing up or sitting suddenly)

• Labored breathing, respiratory tract congestion, wheezing, sore throat, nasal bleeding
• Abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth
• Excessive gas or flatulence
• Increased GGT (a liver enzyme called gamma-glutamyltransferase) in blood, increased liver enzymes in blood
• Rash (or "urticaria"), itching, rash, hair loss, eczema, dry skin, skin redness, acne
• Increased CPK (creatine phosphokinase) in blood, an enzyme that is sometimes released with muscle breakdown
• Muscle spasms, joint stiffness, muscle weakness, neck pain

• Urinary incontinence, frequent urination, painful urination
• Sexual dysfunction, ejaculation disorder, loss of menstrual periods or other cycle problems (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
• Change in gait
• Chest pain, chest discomfort, feeling unwell
• Thickening of the skin
• Falls.

Rare side effects: can affect up to 1 in 10,000 patients

• Eye infection
• Skin inflammation caused by mites, abscess under the skin
• Increased eosinophils (a type of white blood cell) in blood
• Inadequate secretion of the hormone that controls urine volume
• Sugar in the urine
• Life-threatening complications of uncontrolled diabetes
• Decreased blood sugar
• Excessive water intake
• Lack of movement or response while awake (catatonia)
• Confusion
• Somnambulism
• Lack of emotions
• Inability to achieve orgasm
• Neuroleptic malignant syndrome (confusion, decreased or loss of consciousness, high fever, and severe muscle stiffness), problems with blood vessels in 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 pressure in the eyeball)
• Eye movement problems, eye rotation, light sensitivity of the eyes, increased tear production, eye redness
• Atrial fibrillation (abnormal heart rhythm), irregular heart rate
• 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.

• Flush
• Difficulty breathing during sleep (sleep apnea)
• Pulmonary congestion
• Crackling sounds from the lungs
• Pancreatitis, tongue swelling, fecal incontinence, hard stools
• Cracked lips
• Medication-related skin eruption, skin thickening, dandruff
• Muscle fiber rupture and muscle pain (rhabdomyolysis)
• Joint swelling
• Inability to urinate
• Breast discomfort, breast growth, breast enlargement
• Vaginal discharge
• Very low body temperature, chills, feeling thirsty,
• Withdrawal symptoms from the medication
• Accumulation of pus due to skin infection at the injection site, deep skin infection, abscess at the injection site, bruising at the injection site.

Unknown frequency: cannot be estimated from available data

• Peligrosamente 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, rash, and sometimes a decrease in blood pressure
• Excessive water intake
• Sleep-related eating disorder
• Coma due to uncontrolled diabetes
• Head agitation
• Blood clots in the lungs causing chest pain and difficulty breathing. If you experience any of these symptoms, seek medical advice immediately.
• Decreased oxygen in parts of the body (due to decreased blood flow)
• Fast, shallow breathing, pneumonia caused by food aspiration, voice disorder
• Intestinal obstruction, absence of intestinal movement causing obstruction
• Yellow skin and eyes (jaundice)
• Severe allergic reaction with swelling that can affect the throat, causing difficulty breathing
• Decoloration of the skin, scaly skin with itching
• Abnormal posture
• Newborn babies of mothers who have been treated with Xeplion during pregnancy may experience adverse effects of the medication and/or withdrawal symptoms, such as irritability, weak or sustained muscle contractions, agitation, drowsiness, breathing problems, or difficulty feeding

• Priapism (prolonged erection that may require surgical treatment)
• Decreased body temperature
• Dead skin cells at the injection site and ulcer at the injection site.

Reporting of side effects

If you experience any side 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 thenational notification 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.

Do not store at a temperature above 30°C.

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. In this way, you will help protect the environment.

Composition of Xeplion

The active ingredient is paliperidone.

Each pre-filled syringe of Xeplion 25 mg contains 39 mg of palmitate of paliperidone.

Each pre-filled syringe of Xeplion 50 mg contains 78 mg of palmitate of paliperidone.

Each pre-filled syringe of Xeplion 75 mg contains 117 mg of palmitate of paliperidone.

Each pre-filled syringe of Xeplion 100 mg contains 156 mg of palmitate of paliperidone.

Each pre-filled syringe of Xeplion 150 mg contains 234 mg of palmitate of paliperidone.

The other components are:

Polisorbate 20

Polietilenglycol 4000

Citric acid monohydrate

Disodium phosphate anhydrous

Sodium diacetate monohydrate

Sodium hydroxide (for pH adjustment)

Water for injection

Appearance of the product and contents of the pack

Xeplion is a white to off-white prolonged-release injectable suspension, which comes in a pre-filled syringe.

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

Start of treatment pack:

Each pack contains 1 pack of Xeplion 150 mg and 1 pack of Xeplion 100 mg.

Only some pack sizes may be marketed.

Marketing authorisation holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Last update of this leaflet:

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

This information is intended for healthcare professionals only and should be read in conjunction with the full prescribing information (Summary of Product Characteristics).

The injectable suspension is for single use only. It should be visually inspected for any particulate matter before administration. Do not use the product if the syringe is not visually free of particulate matter.

The pack contains a pre-filled syringe and two safety needles (one 22 gauge 1½ inch [38.1 mm x 0.72 mm] needle with a grey coloured shaft and one 23 gauge 1 inch [25.4 mm x 0.64 mm] needle with a blue coloured shaft) for intramuscular injection. Xeplion is also available in a Start of Treatment Kit containing two pre-filled syringes (150 mg + 100 mg) and two additional safety needles.

1. Shake the syringe vigorously for at least 10 seconds to ensure a homogeneous suspension.

1. Select the appropriate needle.

The first dose of Xeplion (150 mg) is administered on Day 1 in the deltoid muscle using the deltoid needle. The second dose of Xeplion (100 mg) is administered also in the deltoid muscle one week later (Day 8) using the deltoid needle.

If the patient is switched from risperidone prolonged-release injectable to Xeplion, the first Xeplion injection (dose range 25 mg to 150 mg) can be administered in the deltoid muscle or gluteus muscle, using the appropriate needle for the injection site, at the time of the next scheduled injection.

Subsequent monthly maintenance injections can be administered in either the deltoid muscle or gluteus muscle using the appropriate needle for the injection site.

For deltoid muscle injection, if the patient weighs <90>23kg, use the 23 gauge 1 inch [25.4 mm x 0.64 mm] needle (needle with blue shaft); if the patient weighs?90 kg, use the 22 gauge 1½ inch [38.1 mm x 0.72 mm] needle (needle with grey shaft).

For gluteus muscle injection, use the 22 gauge 1½ inch [38.1 mm x 0.72 mm] needle (needle with grey shaft).

1. Whileholding the syringe in a vertical position, remove the needle cap by twisting it off.

1. Open the needle safety device blister pack to the middle. Hold the needle safety device cover by the plastic paper of the blister pack that has just been opened. Attach the needle safety device to the luer connection of the syringe by twisting it in a clockwise direction.

1. Separate the needle safety device cover from the needle by pulling the cover straight off along a line. Do not twist the cover, as the needle may become detached from the syringe.

1. Place the syringe with the needle in a vertical position to proceed with the removal of air. Remove air from the syringe by gently pushing the plunger forward.

1. Inject the entire contents slowly and deeply into the selected deltoid or gluteus muscle of the patient.Do not administer by intravascular or subcutaneous route.

1. Once the injection is complete, use the finger or another finger (8a, 8b) or a flat surface (8c) to activate the needle safety device. The device is fully activated when a click is heard. Dispose of the syringe with the needle appropriately.

8a

8b

8c

Unused medicinal product and all materials that have come into contact with it will be disposed of in accordance with local regulations.