XEPLION 25 mg prolonged release suspension for injection

XEPLION is used as a maintenance treatment for the symptoms of schizophrenia in adult patients stabilised on paliperidone or risperidone.

If you have shown responsiveness to paliperidone or risperidone in the past and have mild to moderate symptoms your doctor may start treatment with XEPLION without prior stabilisation with paliperidone or risperidone.

Schizophrenia isa disease with ?positive? and ?negative? symptoms. Positive means an excess of symptoms that are not normally present. For example, a person with schizophrenia may hear voices or see things that are not there (called hallucinations), believe things that are not true (called delusions), or feel unusually suspicious of others. Negative means a lack of behaviours or feelings that are normally present. For example, a person with schizophrenia may appear withdrawn and may not respond at all emotionally or may have trouble speaking in a clear and logical way. People with this disease may also feel depressed, anxious, guilty, or tense.

Do not use XEPLION

• if you are allergic (hypersensitive) to paliperidone or to any of the other ingredients of XEPLION.
• if you are allergic (hypersensitive) to another antipsychotic medicine including the substance risperidone.

Take special care with XEPLION

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

XEPLION should not be used in children and adolescents under 18 years of age.

All medicines have side effects and some of the side effects of XEPLION can worsen the symptoms of other medical conditions. For that reason, it is important to discuss with your doctor any of the following conditions which can potentially worsen during treatment with XEPLION.

• if you have Parkinson?s disease.
• if you have ever been diagnosed with a condition whose symptoms include high temperature and muscle stiffness (also known as Neuroleptic Malignant Syndrome).
• if you have ever experienced abnormal movements of the tongue or face (Tardive Dyskinesia).
• if you are diabetic or prone to diabetes.
• if you have had breast cancer or a tumour in the pituitary gland in your brain
• if you have a heart disease or heart disease treatment that makes you prone to low blood pressure.
• if you have epilepsy.
• if you have a loss of kidney function.
• if you have a loss of liver function.
• if you have prolonged and/or painful erection.
• if you have problems with controlling core body temperature or overheating.
• if you or someone else in your family has a history of blood clots, as antipsychotics have been associated with formation of blood clots.

If you have any of these conditions, please talk to your doctor as he/she may want to adjust your dose or monitor you for a while.

Since XEPLION may reduce your urge to vomit, there is a chance that it may mask the body?s normal response to ingestion of toxic substances or other medical conditions.

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Since XEPLION works primarily in the brain, interference from other medicines (or alcohol) that work in the brain can cause an exaggeration of side effects such as sleepiness or other effects on the brain.

Since XEPLION can lower blood pressure, care should be taken when XEPLION is used with other medicines that lower blood pressure.

XEPLION can reduce the effect of medicines against Parkinson?s disease and restless legs syndrome (e.g. levodopa).

Paliperidone palmitate may cause an electrocardiogram (ECG) abnormality demonstrating a long time for an electrical impulse to travel through a certain part of the heart (known as ?QT prolongation?). Other medicines that have this effect include some medicines used to treat the rhythm of the heart or to treat infection, and other antipsychotics. It is important to notify your doctor of any medicines you are taking to treat such conditions.

If you are prone to develop convulsions, paliperidone palmitate may increase your chance of experiencing them. Other medicines that have this effect include some medicines used to treat depression or to treat infection, and other antipsychotics. It is important to notify your doctor of any medicines you are taking to treat such conditions.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you are pregnant. You should not use XEPLION during pregnancy unless this has been discussed with your doctor.

XEPLION can pass from mother to baby through breast milk and may harm the baby. Therefore, you should not breastfeed when using XEPLION.

Driving and using machines

Dizziness, extreme tiredness and vision problems may occur during treatment with XEPLION (see section 4). This should be considered in cases where full alertness is required, e.g., when driving a car or handling machinery.

Important information about some of the ingredients of XEPLION

This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg dose, i.e., essentially ?sodium free?.

XEPLION is administered by your doctor or other health care professional in a doctor?s office or clinic. Your doctor will tell you when to come into the doctor?s office or clinic for the injection. It is important not to miss your scheduled dose. If you cannot keep your appointment with the doctor, make sure you call him right away so another appointment can be made as soon as possible. XEPLION will be given by intramuscular injection in the upper arm or buttocks. You will receive the first (150 mg) and second (100 mg) injections of paliperidone palmitate approximately 1 week apart. Thereafter, you will receive an injection (ranging from 25 mg to 150 mg) once a month. Depending on your symptoms, your doctor may increase or decrease the amount of medicine you receive by one dose level at the time of your scheduled monthly injection.

Kidney problems

If you have mild kidney problems your doctor may give you a lower dose. If you have moderate or severe kidney problems XEPLION should not be used.

Elderly

If you are elderly and have mild kidney problems your doctor may give you a lower dose.

Liver problems

If you have severe liver problems XEPLION should be used with caution.

If you are given more XEPLION than needed

This medicine will be given to you under medical supervision; it is, therefore, unlikely that you will be given too much.

Patients who have been given too much paliperidone may experience the following symptoms: drowsiness or sedation, fast heart rate, low blood pressure, an abnormal electrocardiogram (electrical tracing of the heart), or slow or abnormal movements of the face, body, arms or legs.

If you stop using XEPLION

If you stop receiving your injections, you will lose the effects of the medicine. You should not stop using this medicine unless told to do so by your doctor as your symptoms may return.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, XEPLION can cause side effects, although not everybody gets them.

Uncommonly, you may experience a severe allergic reaction characterised by fever, swollen mouth, face, lip or tongue, shortness of breath, itching, skin rash and sometimes drop in blood pressure (amounting to an ?anaphylactic reaction?). If this should occur, seek medical attention immediately.

In elderly patients with dementia, medicines in the same group as XEPLION have been associated with side effects including sudden weakness or numbness of the face, arms, or legs, instances of slurred speech, or blurred vision. These symptoms may be associated with stroke. If any of these should occur, even for a short period of time, seek medical attention immediately(see section 2, take special care with XEPLION).

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data).

Very common side effects

• difficulty sleeping
• headache

Common side effects may include:
One of the most well-known side effects of paliperidone is a group of movement problems known as extrapyramidal disorder. Symptoms may include: abnormal muscle movements, abnormal movements of the mouth, tongue or jaw, lockjaw, drooling, slow or sustained muscle contractions, stiff muscles making your movements jerky, slow shuffling walk, muscle spasms, tremor (shaking), abnormal eye movements, involuntary muscle contractions, prolonged contraction of the neck muscles producing an unnatural position of the head, slow movements or restlessness. Sometimes these side effects can be treated with another medicine while you continue on paliperidone.

Other common side effects include:

• injection site pain or other reactions (such as swelling at the injection site). It is important to talk with your doctor if you are experiencing pain after the injections. Your doctor will work with you to ensure that you continue to receive the medicine with as little discomfort as possible.
• infection of the nose, throat, or chest
• weight gain; high blood sugar; high blood triglycerides (a fat)
• irritability
• agitation
• feeling dizzy, sleepy, or less alert
• inner restlessness
• rapid heart rate
• high blood pressure
• nausea; vomiting; abdominal pain or discomfort; diarrhoea; constipation; toothache
• rash
• back pain; pain in extremity
• weakness; fatigue (tiredness)

Uncommon side effects may include:

• allergic reaction
• high level of hormone called ?prolactin? found on a blood test (which may or may not cause symptoms). When symptoms of high prolactin occur, they may include
• in men: breast swelling, difficulty in getting or maintaining erections, or other sexual dysfunction
• in women: leakage of milk from the breasts, missed menstrual periods, or other problems with your cycle
• increased insulin (a hormone in your blood that controls blood sugar levels) in your blood; increased or decreased appetite; increase of cholesterol levels in your blood
• restlessness; nightmares
• fainting episode; convulsion (fits); problems with speech; a restless urge to move parts of your body; dizziness upon standing
• blurry vision
• sensation of spinning (vertigo)
• abnormal electrical tracing of the heart (electrocardiogram or ECG); slow heart rate; rapid heartbeat upon standing; a fluttering or pounding feeling in your chest (palpitations); prolongation of the QT interval from your heart
• low blood pressure upon standing (consequently, some people taking paliperidone may feel faint, dizzy, or may pass out when they stand up or sit up suddenly)
• increase saliva; dry mouth
• hives (or ?nettle rash?); itching
• sensation of stiffness in joints and/or muscles; muscle aches
• development of breasts in men; problems with erections; sexual dysfunction; leakage of milk from the breasts; missed menstrual periods or other problems with your cycle (females)
• itching at the injection site

Rare side effects may include:

• neuroleptic malignant syndrome (confusion, reduced or loss of consciousness, high fever, and severe muscle stiffness); sudden loss of blood supply to brain (stroke)
• eyes rolling in the back of your head; problems with movement of your eyes
• rash on skin related to drug
• stiff neck
• discharge from breasts
• pain at the administration site; reaction at the site of injection; small bump at injection site

The following are a list of additional side effects that have been reported with paliperidone prolonged release tablets:

Common side effects may include:

• infection of the nose and throat
• cough; pain in the throat and upper part of the windpipe; nasal congestion
• indigestion
• joint pain

Uncommon side effects may include:

• urinary tract infection
• sleep disorder
• increase in heart rate in relation to breathing
• low blood pressure
• excessive passing of gas
• muscle pain
• inability to pass urine
• increased fluid retention in the tissue (oedema)

Rare side effects may include:

• sudden swelling of lips and eyes along with difficulty breathing
• sudden weakness or numbness of the face, arms or legs, especially on one side, or instances of slurred speech that last for less than 24 hours (mini-stroke); convulsion (fits) with shaking movements and tense muscles
• left heart block
• restriction in blood supply
• blockage of small bowels
• rash with pimples on your skin
• problems with leaking urine from your bladder
• enlargement with the glands in your breasts; breast pain; ejaculation with semen flowing backwards into the bladder (males)

Side effects with an unknown frequency may include:

• pneumonia caused by breathing stomach contents into your lungs
• swollen tongue
• prolonged and painful erection. The patient is advised to seek medical attention if this prolonged and painful erection is not resolved within 3-4 hours.
• blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any of these symptoms seek medical advice immediately.

Since paliperidone is a compound resulting from the breakdown of risperidone in the human body, any side effects that may occur after the ingestion of risperidone (another antipsychotic medicine) may also occur with XEPLION. For more information on what these side effects are, speak with your doctor.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of reach and sight of children.

Do not use XEPLION after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What XEPLION contains

The active substance is paliperidone.
Each pre-filled syringe contains 39 mg paliperidone palmitate equivalent to 25 mg paliperidone.

The other ingredients are:
Polysorbate 20

Polyethylene glycol 4000
Citric acid monohydrate
Disodium hydrogen phosphate anhydrous
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Water for injection

What XEPLION looks like and contents of the pack

XEPLION is a white to off-white prolonged release suspension for injection in a pre-filled syringe that is provided by your doctor?s office or clinic.

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

Marketing Authorisation Holder and Manufacturer

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

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien JANSSEN-CILAG N.V.S.A. TelTél 32 14 64 94 11 LuxembourgLuxemburg JANSSEN-CILAG N.V.S.A. TelTél 32 14 64 94 11

Johnson Johnson, .359 2 489 9400 Magyarország JANSSEN-CILAG Kft. Tel. 36 23 513 800

eská republika JANSSEN-CILAG s.r.o. Tel420 227 012 222 Malta AM MANGION LTD Tel 356 2397 6000

Danmark JANSSEN-CILAG AS Tlf 45 45 94 82 82 Nederland JANSSEN-CILAG B.V. Tel 31 13 583 73 73

Deutschland JANSSEN-CILAG GmbH Tel 49 2137-955-955 Norge JANSSEN-CILAG AS Tlf 47 24 12 65 00

Eesti JANSSEN-CILAG Tel. 372 617 7410 Österreich JANSSEN-CILAG PHARMA GmbH Tel 43 1 610 300

JANSSEN-CILAG T 30 210 80 90 000 Polska JANSSENCILAG Polska Sp. z o.o. Tel. 48 22 237 6000

España JANSSEN-CILAG, S.A. Tel 34 91 722 81 00 Portugal JANSSEN-CILAG FARMACEUTICA, LDA Tel 351 21-4368835

France JANSSEN-CILAG Tel 0800 25 50 75 33 1 55 00 44 44 România Johnson Johnson d.o.o. Tel 40 21 207 1800

Ireland JANSSEN-CILAG Ltd. Tel 44 1 494 567 567 Slovenija Johnson Johnson d.o.o. Tel 386 1401 18 30

Slovenská republika JOHNSON JOHNSON S.R.O, Tel 421 233 552 600 Ísland JANSSEN-CILAG Co Vistor hf Sími 354 535 7000

Italia JANSSEN-CILAG SpA Tel 39 022510.1 SuomiFinland JANSSEN-CILAG OY PuhTel 358 207 531 300

T 357 22 755 214 Sverige JANSSEN-CILAG AB Tel 46 8 626 50 00

United Kingdom JANSSEN-CILAG Ltd. Tel 44 1494 567 567 Latvija JANSSEN-CILAG Polska Sp. z.o.o. filile Latvij Talr. 371 6789 3561

Lietuva
Johnson & Johnson UAB
Tel.: +370 5 278 68 88

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only:

The suspension for injection is for single use only. It should be inspected visually for foreign matter before administration. Do not use if the syringe is not visually free of foreign matter.

The pack contains a pre-filled syringe and 2 safety needles (a 1½-inch 22 gauge needle [38.1 mm x 0.72 mm] and a 1-inch 23 gauge needle [25.4 mm x 0.64 mm]) for intramuscular injection.

1. Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous suspension.

2. Select the appropriate needle.

For DELTOID injection, if the patient weighs < 90 kg, use the 1-inch, 23 gauge needle (25.4 mm x 0.64 mm) (needle with blue colored hub); if the patient weighs ? 90 kg, use the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm) (needle with grey coloured hub).

For GLUTEAL injection, use the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm) (needle with grey coloured hub).

3. While holding the syringe upright, remove the rubber tip cap with a twisting motion.

4. Peel the safety needle blister pouch half way open. Grasp the needle sheath using the plastic peel pouch. Attach the safety needle to the luer connection of the syringe with an easy clockwise twisting motion.

5. Pull the needle sheath away from the needle with a straight pull. Do not twist the sheath as the needle may be loosened from the syringe.

6. Bring the syringe with the attached needle in upright position to de-aerate. De-aerate the syringe by moving the plunger rod carefully forward.

7. Inject the entire contents intramuscularly into the selected deltoid or gluteal muscle of the patient. Do not administer intravascularly or subcutaneously.

8. After the injection is complete, use either thumb or finger of one hand (8a, 8b) or a flat surface (8c) to activate the needle protection system. The system is fully activated when a ?click? is heard. Discard the syringe with needle appropriately.

8a

8b

8c

Any unused product or waste material should be disposed of in accordance with local requirements.