Xeplion 50 mg prolonged-release injectable suspension

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Xeplion 25 mg prolonged-release injectable suspension

Xeplion 50 mg prolonged-release injectable suspension

Xeplion 75 mg prolonged-release injectable suspension

Xeplion 100 mg prolonged-release injectable suspension

Xeplion 150 mg prolonged-release injectable suspension

Paliperidone

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, ask your doctor, pharmacist or nurse.

• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

1. What Xeplion is and what it is used for

2. What you need to know before using Xeplion

3. How to use Xeplion

4. Possible side effects

5. How to store Xeplion

6. Contents of the pack and other information

1. What Xeplion is and what it is used for

Xeplion contains the active substance paliperidone, which belongs to the class of antipsychotic medicines. It is used as maintenance treatment for the symptoms of schizophrenia in adult patients who have been stabilized on paliperidone or risperidone.

If you have previously responded to paliperidone or risperidone and have mild or moderate symptoms, your doctor may start 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 not normally present. For example, a person with schizophrenia may hear voices or see things that do not exist (called hallucinations), have false beliefs (called delusions), or have abnormally high levels of distrust toward others. Negative refers to the absence of behaviours or feelings that are normally present. For example, a person with schizophrenia may become withdrawn and unresponsive to emotional stimuli, or may have difficulty speaking in a clear and logical manner. People with this disorder may also feel depressed, anxious, guilty, or tense.

Xeplion can help relieve the symptoms of your illness and help prevent them from returning.

2. What you need to know before using Xeplion

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 medicine, including risperidone.

Warnings and precautions

Talk to 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 that you discuss with your doctor if you have any of the following conditions, which could worsen during treatment with this medicine:

• if you have Parkinson's disease

• if you have ever been diagnosed with a condition whose symptoms include high body 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 have previously had low levels of white blood cells in the blood (which may or may not have been caused by other medicines)

• if you are diabetic or have a tendency towards diabetes

• if you have had breast cancer or a tumor in the pituitary gland of the brain

• if you have heart disease or are receiving treatment for heart conditions that may make you more prone to a drop in blood pressure

• if you have low blood pressure when standing up or getting up suddenly

• if you have epilepsy

• if you have kidney problems

• if you have liver problems

• if you have prolonged and/or painful erection

• if you have difficulty regulating body temperature or are overheated

• if you have abnormally high levels of the hormone prolactin in the blood or if you have a tumor that may be prolactin-dependent

• if you or someone in your family has a history of blood clots, as antipsychotics have been associated with blood clot formation.

If you have any of these conditions, please consult your doctor, as a dose adjustment or monitoring may be necessary.

Because, very rarely, patients treated with this medicine have developed a dangerously low number of a type of white blood cells needed to fight infections, your doctor may check your white blood cell count.

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

This medicine may cause weight gain. Significant weight gain may negatively affect your health. Your doctor will regularly monitor your weight.

Diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed in patients treated with this medicine. Your doctor should check for signs of increased blood sugar. In patients with pre-existing diabetes mellitus, blood sugar should be monitored regularly.

Because this medicine may reduce the urge to vomit, it may mask the body's normal response to the ingestion of toxic substances or other medical conditions.

During eye surgery for lens clouding (cataracts), the pupil (the black circle in the center of the eye) may not dilate as needed. In addition, the iris (the colored part of the eye) may become floppy during surgery, which may cause eye damage. If you are considering eye surgery, make sure to inform your ophthalmologist that you are taking this medicine.

Children and adolescents

Do not use this medicine in individuals under 18 years of age.

Using Xeplion with other medicines

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Taking this medicine together with carbamazepine (an antiepileptic and mood stabilizer) may require a change in the dose of this medicine.

Because this medicine acts mainly in the brain, interactions with other medicines that also act on the brain may increase side effects such as drowsiness or other brain effects, such as with other psychiatric medicines, opioids, antihistamines, and sleeping medicines.

Because this medicine may lower blood pressure, you should be cautious when using it with other medicines that also 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) indicating that it takes longer for an electrical impulse to travel through a certain part of the heart (known as "QT interval prolongation"). Other medicines that have this effect include some medicines used to treat heart rhythm or infections, as well as other antipsychotics.

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

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

Xeplion and alcohol

Alcohol should be avoided.

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 medicine. You should 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 during the third trimester of pregnancy (last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. 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, you should not breastfeed while using this medicine.

Driving and using machines

While being treated with this medicine, dizziness, extreme tiredness, and vision problems may occur (see section 4). This should be taken into account when maximum attention is required, e.g., when driving or operating machinery.

Xeplion contains sodium

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

3. How to use Xeplion

Your doctor or other healthcare professional will administer this medicine to you. Your doctor will tell you when the next injection should be given. It is important not to miss any of the scheduled doses. If you are unable to attend your appointment, make sure to contact your doctor immediately to arrange another appointment as soon as possible.

You will receive the first injection (150 mg) and the second injection (100 mg) of this medicine in the upper arm, approximately one week apart. After that, 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 injectable risperidone to this medicine, you will receive the first injection of this medicine (between 25 mg and 150 mg) in the upper arm or buttocks at your next scheduled injection. After that, you will receive an injection (between 25 mg and 150 mg) in the upper arm or buttocks once a month.

Depending on your symptoms, your doctor may increase or decrease the amount of medicine you receive to a different dose level at the time of your scheduled monthly injection.

Patients with kidney problems

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

Elderly patients

Your doctor may reduce the dose of this medicine if your kidney function is reduced.

If you receive more Xeplion than you should

You will receive this medicine under medical supervision; therefore, it is unlikely that you will receive an overdose.

Patients who have received an overdose of paliperidone may experience the following symptoms: drowsiness or sedation, rapid heartbeat, low blood pressure, abnormalities in the electrocardiogram (electrical tracing of the heart), 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 medicine will be lost. You should not stop using this medicine unless instructed by your doctor, as your symptoms may return.

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

4. Possible adverse effects

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

Tell your doctor immediately if:

• you develop blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg), which may travel through 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 mental status 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 develop fever, muscle stiffness, sweating, or decreased level of consciousness (a disorder known as "Neuroleptic Malignant Syndrome"). Immediate medical treatment may be required.

• you are male and experience a prolonged or painful erection. This is known as priapism. Immediate medical treatment may be needed.

• you experience involuntary rhythmic movements of the tongue, mouth, or face. Discontinuation of paliperidone may be necessary.

• you develop 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"). Even if you have previously tolerated oral risperidone or oral paliperidone, allergic reactions have occasionally occurred after receiving paliperidone injections.

• you are scheduled for eye surgery, make sure to inform your ophthalmologist that you are taking this medicine. During cataract surgery, the iris (the colored part of the eye) may become floppy during the procedure (known as "floppy iris syndrome"), which could lead to eye damage.

• you have a dangerously low number of a type of white blood cells necessary to fight blood infections.

The following adverse effects may occur:

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

• difficulty falling or staying asleep.

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

• symptoms of common cold, urinary tract infection, feeling as if you have the flu

• Xeplion may increase levels of a hormone called "prolactin" detectable in blood tests (which may or may not cause symptoms). When symptoms of elevated prolactin occur, they may include (in men) breast swelling, difficulty achieving or maintaining erections, or other sexual dysfunction; (in women) breast discomfort, milk secretion from the breasts, loss of menstrual periods, or other menstrual cycle problems.

• increased blood sugar, weight gain, weight loss, decreased appetite

• irritability, depression, anxiety

• parkinsonism: This condition may include slow or altered movement, a sensation of muscle stiffness or tightness (causing jerky movements), and sometimes a feeling of "freezing" of movement that then restarts. Other signs of parkinsonism include shuffling slow gait, resting tremor, increased saliva and/or drooling, and loss of facial expressiveness

• restlessness, drowsiness, or reduced alertness

• dystonia: A disorder involving involuntary, slow, or sustained muscle contractions. Although any part of the body may be affected (and may result in abnormal postures), dystonia frequently affects facial muscles, including abnormal eye, mouth, tongue, or jaw movements

• dizziness

• dyskinesia: This disorder involves involuntary muscle movements and may include repetitive, spasmodic, or twisting movements, or spasms

• tremor (agitation)

• headache

• rapid heartbeat

• increased blood pressure

• cough, nasal congestion

• abdominal pain, vomiting, nausea, constipation, diarrhea, indigestion, toothache

• increased liver transaminases in blood

• bone or muscle pain, back pain, joint pain

• absence of menstruation

• milk secretion from the breasts

• fever, weakness, fatigue (tiredness)

• a reaction at the injection site, including itching, pain, or swelling.

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

• pneumonia, chest infection (bronchitis), respiratory tract infection, nasal infection, bladder infection, ear infection, fungal nail infection, tonsillitis, skin infection

• decreased number of white blood cells, decreased number of a type of white blood cells that help fight infections, decreased platelets (blood cells that help 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 reduced body weight

• increased blood triglycerides (fat), increased blood cholesterol

• sleep disorder, euphoria (mania), decreased sexual desire, nervousness, nightmares

• tardive dyskinesia (involuntary spasms or spasmodic movements of the face, tongue, or other body parts). Inform your doctor immediately if you experience involuntary rhythmic movements of the tongue, mouth, or face. Discontinuation of this medicine may be necessary.

• fainting, restlessness causing movement of body parts, dizziness upon standing, attention disturbance, speech problems, loss or changes in taste, decreased skin sensitivity to pain or touch, tingling, prickling, or numbness of the skin

• blurred vision, eye infection or "red eye," dry eyes

• sensation of spinning (vertigo), ringing in the ears, ear pain

• interruption of conduction between upper and lower parts of the heart, abnormal electrical activity of the heart, QT interval prolongation in the heart, rapid heartbeat upon standing, slow heartbeat, abnormalities in the heart's electrical tracing (electrocardiogram or ECG), sensation of fluttering or pounding in the chest (palpitations)

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

• shortness of breath, respiratory congestion, wheezing, sore throat, nosebleeds

• abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth

• excess gas or flatulence

• increased GGT (a liver enzyme called gamma-glutamyltransferase) in blood, increased liver enzymes in blood

• hives (or "urticaria"), itching, rash, hair loss, eczema, dry skin, skin redness, acne

• increased CPK (creatine phosphokinase) in blood, an enzyme sometimes released during muscle breakdown

• muscle spasms, joint stiffness, muscle weakness, neck pain

• urinary incontinence (loss of bladder control), frequent urination, painful urination

• erectile dysfunction, ejaculation disorder, absence of menstrual periods or other menstrual cycle problems (women), breast development in men, sexual dysfunction, breast pain

• swelling of the face, mouth, eyes, or lips, body swelling, arms or legs swelling

• increased body temperature

• change in walking pattern

• chest pain, chest discomfort, feeling of uneasiness

• hardening of the skin

• falls.

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

• eye infection

• skin inflammation caused by mites, subcutaneous abscess

• increased eosinophils (a type of white blood cell) in blood

• inappropriate secretion of the hormone controlling urine volume

• sugar in urine

• potentially life-threatening complications of uncontrolled diabetes

• decreased blood sugar

• excessive water intake

• lack of movement or response while awake (catatonia)

• confusion

• sleepwalking

• absence of emotions

• inability to achieve orgasm

• neuroleptic malignant syndrome (confusion, decreased or loss of consciousness, high fever, severe muscle rigidity), brain blood vessel disorders, including sudden loss of blood supply to the brain (stroke or "mini" stroke), unresponsiveness to stimuli, loss of consciousness, decreased level of consciousness, seizures (epileptic fits), balance disorder

• abnormal coordination

• glaucoma (increased pressure in the eyeball)

• eye movement disorders, eye rolling, light sensitivity of the eyes, increased tearing, eye redness

• atrial fibrillation (abnormal heart rhythm), irregular heartbeat

• blood clots in the veins, especially in the legs (symptoms include leg swelling, pain, and redness). If you experience any of these symptoms, seek medical help immediately.

• flushing

• difficulty breathing during sleep (sleep apnea)

• pulmonary congestion

• crackling lung sounds

• pancreatitis, tongue swelling, fecal incontinence, very hard stools

• cracked lips

• drug-related skin rash, skin thickening, dandruff

• muscle fiber breakdown and muscle pain (rhabdomyolysis)

• joint swelling

• inability to urinate

• breast discomfort, enlargement of breast glands, breast growth

• vaginal discharge

• very low body temperature, chills, feeling of thirst

• medication withdrawal symptoms

• pus accumulation due to infection at the injection site, deep skin infection, cyst at the injection site, bruising at the injection site.

Frequency not known: cannot be estimated from available data

• dangerously low number of white blood cells necessary to fight infections

• severe allergic reaction characterized by fever, swelling of the mouth, face, lips, or tongue, breathing difficulty, itching, skin rash, and sometimes low blood pressure

• dangerously excessive water intake

• sleep-related eating disorder

• coma due to uncontrolled diabetes

• head agitation

• blood clots in the lungs causing chest pain and breathing difficulty. If you experience any of these symptoms, see a doctor immediately.

• decreased oxygen in parts of the body (due to reduced blood flow)

• rapid, shallow breathing, aspiration pneumonia (pneumonia caused by inhaling food), voice disorder

• intestinal obstruction, absence of intestinal movement causing obstruction

• yellowing of the skin and eyes (jaundice)

• severe allergic reaction with swelling that may affect the throat, causing breathing difficulty

• skin discoloration, scaly and itchy skin or scalp

• abnormal posture

• newborn babies of mothers treated with Xeplion during pregnancy may experience adverse effects from the medicine and/or withdrawal symptoms, such as irritability, weak or sustained muscle contractions, agitation, drowsiness, breathing problems, or feeding difficulties

• priapism (a prolonged erection that may require surgical treatment)

• decreased body temperature

• dead skin cells at the injection site and ulceration at the injection site.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the national reporting system detailed in Appendix V.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Xeplion

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

Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.

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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Xeplion

The active substance is paliperidone.

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

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

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

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

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

The other components are:

Polysorbate 20

Polyethylene glycol 4000

Monohydrate citric acid

Disodium hydrogen phosphate anhydrous

Sodium dihydrogen phosphate monohydrate

Sodium hydroxide (for pH adjustment)

Water for injections

Appearance of the product and contents of the pack

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

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

Initiation pack:

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

Only certain 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

More information about this medicinal product can be obtained by contacting the local representative of the Marketing Authorisation Holder.

Belgium/Belgium/Belgium Janssen-Cilag NV Tel/Tel: +32 14 64 94 11	Lithuania UAB “JOHNSON & JOHNSON” Tel: +370 5 278 68 88
Bulgaria “JOHNSON & JOHNSON” EOOD Tel: +359 2 489 94 00	Luxembourg/Luxembourg Janssen-Cilag NV Tél/Tel: +32 14 64 94 11
Czech Republic Janssen-Cilag s.r.o. Tel: +420 227 012 227	Hungary Janssen-Cilag Kft. Tel.: +36 1 884 2858
Denmark Janssen-Cilag A/S Tlf: +45 45 94 82 82	Malta AM MANGION LTD. Tel: +356 2397 6000
Germany Janssen-Cilag GmbH Tel: +49 2137-955-955	Netherlands Janssen-Cilag B.V. Tel: +31 76 711 1111
Estonia UAB “JOHNSON & JOHNSON” Estonia branch Tel.: +372 617 7410	Norway Janssen-Cilag AS Tlf: +47 24 12 65 00
Greece Janssen-Cilag Pharmaceutical S.A. Tel: +30 210 80 90 000	Austria Janssen-Cilag Pharma GmbH Tel: +43 1 610 300
Spain Janssen-Cilag, S.A. Tel: +34 91 722 81 00	Poland Janssen-Cilag Polska Sp. z o.o. Tel.: +48 22 237 60 00
France Janssen-Cilag Tel: 0 800 25 50 75 / +33 1 55 00 40 03	Portugal Janssen-Cilag Farmacêutica, Lda. Tel: +351 214 368 600
Croatia Johnson & Johnson S.E. d.o.o. Tel: +385 1 6610 700	Romania Johnson & Johnson România SRL Tel: +40 21 207 1800
Ireland Janssen Sciences Ireland UC Tel: +353 1 800 709 122	Slovenia Johnson & Johnson d.o.o. Tel: +386 1 401 18 00
Iceland Janssen-Cilag AB C/o Vistor hf Sími: +354 535 7000	Slovakia Johnson & Johnson s.r.o. Tel: +421 232 408 400
Italy Janssen-Cilag SpA Tel: +39 02 2510 1	Finland Janssen-Cilag Oy Puh/Tel: +358 207 531 300
Cyprus Varnavas Hadjipanagis Ltd Tel: +357 22 207 700	Sweden Janssen-Cilag AB Tel: +46 8 626 50 00
Latvia UAB “JOHNSON & JOHNSON” Latvia branch Tel: +371 6789 3561	United Kingdom Janssen-Cilag Ltd. Tel: +44 1 494 567 444

Date of the most recent review of this leaflet:

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

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

The injectable suspension is for single use only. It should be visually inspected for any extraneous particulate matter prior to administration. Do not use the product if the syringe is not visually free from extraneous 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 and one 23-gauge 1-inch [25.4 mm x 0.64 mm] needle) for intramuscular injection. Xeplion is also available as a Treatment Initiation Kit containing two pre-filled syringes (150 mg + 100 mg) and two additional safety needles.

1. Gauge 22 x 11/2” (Gray-colored needle)

2. Gauge 23 x 1” (Blue-colored needle)

3. Pre-filled syringe

4. Needle

5. Needle cap

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

1. Select the appropriate needle.

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

If a patient is being switched from long-acting injectable risperidone to Xeplion, the first injection of Xeplion (dose range 25 mg to 150 mg) may be administered into either the DELTOID or GLUTEAL muscle, using the appropriate needle for the injection site, at the time of the next scheduled injection.

Subsequently, monthly maintenance injections may be administered into either the DELTOID or GLUTEAL muscle using the appropriate needle for the injection site.

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

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

1. While holding the syringe in an upright position, remove the rubber tip cap with a twisting motion.

1. Open the safety needle blister pack halfway. Hold the needle cap using the plastic paper of the opened pouch. Attach the safety needle to the syringe's luer connector with a simple clockwise twisting motion.

1. Pull the cap straight off to separate it from the needle. Do not twist the cap, as the needle could detach from the syringe.

1. Position the syringe with the needle attached in a vertical position to remove air. Remove air from the syringe by carefully pushing the plunger forward.

1. Inject the entire contents slowly and deeply into the selected deltoid or gluteal muscle of the patient. The product must not be administered intravascularly or subcutaneously.

2. After completing the injection, use the thumb or another finger of the hand (8a, 8b), or a flat surface (8c) to activate the needle protection system. The system is fully activated when a click is heard. Dispose of the syringe with the needle properly.

8a

8b

8c

Disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations.