Paliperidone +pharma

Package leaflet: Information for the user

Paliperidone +pharma, 25 mg, prolonged-release injectable suspension
in pre-filled syringe
Paliperidone +pharma, 50 mg, prolonged-release injectable suspension
in pre-filled syringe
Paliperidone +pharma, 75 mg, prolonged-release injectable suspension
in pre-filled syringe
Paliperidone +pharma, 100 mg, prolonged-release injectable suspension
in pre-filled syringe
Paliperidone +pharma, 150 mg, prolonged-release injectable suspension
in pre-filled syringe
Starter pack
Paliperidone +pharma, 100 mg + 150 mg, prolonged-release injectable suspension
in pre-filled syringe
Paliperidonum
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Paliperidone +pharma is and what it is used for
2. What you need to know before you use Paliperidone +pharma
3. How to use Paliperidone +pharma
4. Possible side effects
5. How to store Paliperidone +pharma
6. Contents of the pack and other information

1. What Paliperidone +pharma is and what it is used for

Paliperidone +pharma contains the active substance paliperidone, which belongs to a group of medicines called antipsychotics. It is used for the maintenance treatment of symptoms of schizophrenia in adult patients who have been stabilised on paliperidone or risperidone therapy.
For patients who previously responded to paliperidone or risperidone and whose current psychotic symptoms are mild to moderate, a doctor may initiate treatment with Paliperidone +pharma without prior stabilisation with paliperidone or risperidone.
Schizophrenia is a disorder with "positive" and "negative" symptoms. Positive symptoms refer to the presence of symptoms that normally do not occur. For example, a person with schizophrenia may hear voices or see things that are not there (hallucinations), believe things that are not true (delusions), or be excessively suspicious of others. Negative symptoms refer to the absence of normal behaviours or emotions. For example, a person with schizophrenia may appear withdrawn, emotionally flat, and unresponsive, or may have difficulty speaking in a clear and logical way. People with this condition may also experience depression, anxiety, feelings of guilt, or tension.
Paliperidone +pharma helps to reduce the symptoms of the illness and prevent their recurrence.

2. Important information before using Paliperidone +pharma

When not to use Paliperidone +pharma

• if the patient is allergic to paliperidone or any of the other ingredients of this medicine (listed in section 6)
• if the patient is allergic to another antipsychotic medicine, including the substance risperidone.

Warnings and precautions
Before starting treatment with Paliperidone +pharma, discuss this with your doctor, pharmacist, or
nurse.
The use of paliperidone has not been studied in elderly patients with dementia. However, in such
patients treated with other similar types of medicines, there may be an increased risk of stroke or
death (see section 4 "Possible side effects").
All medicines can cause side effects. Some side effects of this medicine may worsen symptoms of other medical conditions. Therefore, it is important to discuss with your doctor any of the following conditions that could potentially worsen during treatment with this medicine:

• if the patient has Parkinson's disease
• if the patient has ever been diagnosed with a condition characterized by symptoms such as high fever and muscle stiffness (also known as neuroleptic malignant syndrome)
• if the patient has ever experienced involuntary movements of the tongue or facial muscles (tardive dyskinesia)
• if the patient has had a low white blood cell count in the past (whether or not caused by other medicines)
• if the patient has diabetes or is predisposed to developing diabetes
• if the patient has breast cancer or a pituitary gland tumor
• if the patient has heart disease or is being treated for heart disease that may predispose to low blood pressure
• if the patient experiences low blood pressure upon sudden change to standing or sitting position
• if the patient has epilepsy
• if the patient has kidney function disorders
• if the patient has liver function disorders
• if the patient experiences prolonged and/or painful erection
• if the patient has problems with body temperature regulation or overheating
• if the patient has abnormally increased levels of prolactin hormone in the blood or suspected prolactin-dependent tumor
• if the patient or a family member has a history of blood clots in blood vessels, as antipsychotic medicines are associated with their development

If the patient meets any of the above criteria, they should consult their doctor, who may adjust the dose or monitor the patient periodically.
The treating doctor may order a white blood cell count test, as very rarely, dangerously low levels of a certain type of white blood cells necessary for fighting infections have been observed in patients taking paliperidone.
Even if the patient previously tolerated oral paliperidone or risperidone well, allergic reactions may rarely occur after injections of Paliperidone +pharma. Seek immediate medical help if the patient develops rash, throat swelling, itching, or difficulty breathing, as these may be symptoms of a severe allergic reaction.
This medicine may cause weight gain. Significant weight gain may negatively affect the patient's health. The treating doctor will regularly monitor the patient's body weight.
The treating doctor will check for symptoms of elevated blood sugar levels, as new-onset diabetes or worsening of pre-existing diabetes has been reported in patients taking this medicine. Patients with pre-existing diabetes should have their blood glucose levels monitored regularly.
Since this medicine may reduce the vomiting reflex, there is a risk that it may mask the body's normal response to ingestion of toxic substances or other medical conditions.
During cataract surgery, the pupil (black circle in the center of the eye) may not dilate sufficiently. Also, the iris of the eye (colored part) may be floppy during surgery, which could lead to eye damage. If the patient is scheduled for eye surgery, inform the ophthalmologist about taking this medicine.

Children and adolescents
This medicine is not intended for use in individuals under 18 years of age.

Paliperidone +pharma and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Taking this medicine together with carbamazepine (an antiepileptic and mood-stabilizing medicine) may require adjustment of the dose of this medicine.
Since this medicine acts mainly on the brain, interactions with other medicines that also affect the brain, such as other psychiatric medicines, opioids, antihistamines, and sleeping medicines, may increase side effects such as drowsiness or other brain-related effects.
This medicine may lower blood pressure; therefore, caution is advised when using it together with other medicines that lower blood pressure.
This medicine may weaken the effect of medicines used in Parkinson's disease and restless legs syndrome (e.g., levodopa).
This medicine may cause abnormalities in the electrocardiogram (ECG), manifesting as prolongation of the time it takes for an electrical impulse to pass through a certain part of the heart (known as "QT interval prolongation"). Other medicines with this effect include those used to regulate heart rhythm or treat infections, as well as other antipsychotic medicines.
If the patient is prone to seizures, this medicine may increase the risk of their occurrence. Other medicines with this effect include certain antidepressants or antimicrobials, as well as other antipsychotics.
Caution is advised when using Paliperidone +pharma together with medicines that increase central nervous system activity (psychostimulants, such as methylphenidate).

Paliperidone +pharma and alcohol
Alcohol consumption should be avoided.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
This medicine should not be used during pregnancy unless discussed with a doctor. Newborns whose mothers took paliperidone during the third trimester (last 3 months of pregnancy) may experience the following symptoms: tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If such symptoms are observed in your child, contact your doctor.
This medicine may pass from the mother's body into breast milk and harm the infant. Therefore, breastfeeding must not be performed while taking this medicine.

Driving and operating machinery
During treatment with this medicine, dizziness, extreme fatigue, and visual disturbances may occur (see section 4). These effects should be taken into account in situations requiring full alertness, such as driving or operating machinery.

Paliperidone +pharma contains sodium and polysorbate
The medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".
The medicine contains 12 mg of polysorbate per ml, equivalent to 12 mg/ml. Polysorbates may cause allergic reactions. Inform the doctor if the patient has known allergic reactions.

3. How to use Paliperidone +pharma

The medicine is administered by a doctor or other medical personnel. It will be injected intramuscularly. Your doctor will inform you when the next injection should be given. It is important not to miss a scheduled dose. If you are unable to keep the scheduled appointment, you must inform your doctor immediately so that a new appointment can be arranged as soon as possible.

The first (150 mg) and second (100 mg) injections of this medicine will be given into the upper arm, approximately one week apart. After that, an injection will be given once a month (at a dose ranging from 25 mg to 150 mg) into the upper arm or buttock.

If your doctor decides to switch treatment from long-acting risperidone injections to this medicine, the first injection of this medicine (at a dose ranging from 25 mg to 150 mg) will be administered into the upper arm or buttock on the day of your next scheduled injection. After that, monthly injections (at a dose ranging from 25 mg to 150 mg) will be given into the upper arm or buttock.

Depending on the symptoms experienced by the patient, the doctor may increase or decrease the administered dose by one level during the scheduled monthly injection.

Patients with renal impairment
The doctor will adjust the dose of the medicine based on kidney function. If the patient has mild renal impairment, the doctor may reduce the dose. This medicine should not be used in patients with moderate or severe renal impairment.

Elderly patients
The doctor may reduce the dose if the patient has impaired kidney function.

Overdose of Paliperidone +pharma
This medicine will be administered under medical supervision, so overdose is unlikely.
In patients who have received an excessive dose of paliperidone, the following symptoms may occur:
drowsiness and sedation, increased heart rate, low blood pressure, abnormal ECG (electrocardiogram) findings, or slowed or abnormal muscle movements of the face, body, arms, or legs.

Stopping treatment with Paliperidone +pharma
If the patient stops receiving the injections, the medicine will no longer work. Do not discontinue treatment unless instructed by the doctor, as symptoms of the illness may return.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should immediately inform your doctor if:

• the patient develops 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 such symptoms occur, seek immediate medical help.
• the patient with dementia experiences a sudden change in mental status or sudden weakness, or facial, arm or leg numbness, especially on one side, or speech disturbances, even if they last only a short time. These symptoms may indicate a stroke.
• the patient develops fever, muscle stiffness, sweating or decreased level of consciousness (a condition called "neuroleptic malignant syndrome"). Immediate treatment may be necessary.
• the male patient experiences prolonged or painful erection. This condition is known as "priapism". Immediate treatment may be necessary.
• involuntary rhythmic movements of the tongue, mouth or face occur. Discontinuation of paliperidone treatment may be necessary.
• the patient develops a severe allergic reaction characterised by: fever, swelling of the lips, face, tongue or throat, breathing difficulties, itching, skin rash, and sometimes low blood pressure (known as "anaphylactic reaction"). Even if the patient previously tolerated risperidone or paliperidone taken orally, allergic reactions may rarely occur after paliperidone injections.
• the patient has a planned eye surgery, the ophthalmologist should be informed about taking this medicine. During cataract removal, floppy iris syndrome may occur, which may lead to eye damage.
• the patient has a dangerously low number of certain white blood cells essential for fighting infections.

The following side effects may occur:
Very common (may occur in more than 1 in 10 patients)

• difficulty falling asleep or waking up

Common (may occur in less than 1 in 10 patients)

• cold symptoms, urinary tract infection, flu-like symptoms

• Paliperidone +pharma may increase the level of the hormone prolactin in the blood (this may, but does not necessarily, cause symptoms). If symptoms of increased prolactin occur, they may include in men: breast swelling, difficulty achieving or maintaining erection or other sexual disturbances. In women, they may include: breast discomfort, milk leakage from the breasts, absence of menstrual bleeding or other menstrual cycle disturbances.

• high blood sugar levels, weight gain, weight loss, decreased appetite

• irritability, depression, anxiety

• parkinsonism: this condition may include slow or abnormal movements, feeling of stiffness or muscle tension (causing jerky, abrupt movements of the patient), and sometimes even a feeling of "freezing" of movements followed by sudden release. Other symptoms of parkinsonism include:
  slow shuffling gait, resting tremor, increased salivation/drooling, and lack of
  emotional expression on the face

• psychomotor restlessness, feeling of drowsiness or reduced alertness

• dystonia: this condition involves slow or sustained involuntary muscle contractions. Although it may affect any part of the body (possibly resulting in abnormal body posture), dystonia most commonly affects facial muscles, including abnormal eye, mouth, tongue or jaw movements

• dizziness

• dyskinesia: this condition involves involuntary muscle movements and may present as repetitive, spasmodic or twisting movements or jerks

• tremor

• headache

• rapid heartbeat

• high blood pressure

• cough, stuffy nose

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

• increased liver enzyme activity in blood

• bone or muscle pain, back pain, joint pain

• absence of menstruation

• fever, weakness, fatigue

• injection site reaction, including itching, pain or swelling

Uncommon (may occur in less than 1 in 100 patients)

• pneumonia, bronchitis, respiratory tract infections, sinus infection, bladder infection, ear infection, fungal nail infection, tonsillitis, skin infection
• decreased number of white blood cells, decreased number of certain white blood cells protecting against infections, anaemia
• allergic reaction
• occurrence or worsening of pre-existing diabetes, increased blood insulin levels (hormone regulating blood sugar levels)
• increased appetite
• loss of appetite leading to malnutrition and low body weight
• high blood triglyceride (fats) levels, increased blood cholesterol levels
• sleep disturbances, elevated mood (mania), decreased libido, nervousness, nightmares
• tardive dyskinesia (twitching or jerking, uncontrolled movements of the face, tongue or other body parts). Inform your doctor immediately if involuntary rhythmic movements of the tongue, mouth or face occur. Discontinuation of this medicine may be necessary.
• fainting, need to move body parts, dizziness upon standing, difficulty concentrating, speech difficulties, loss or altered sense of taste, reduced sensitivity to pain and touch on the skin, tingling, prickling or numbness of the skin
• blurred vision, eye infection or conjunctivitis, dry eyes
• feeling of dizziness, ringing in the ears, ear pain
• heart conduction block, abnormal conduction of electrical impulses in the heart, QT interval prolongation on ECG, rapid heartbeat upon standing, slow heart rate, abnormal ECG recording, palpitations (awareness of heartbeats)
• low blood pressure, low blood pressure upon standing (as a result, some patients taking this medicine may faint, feel dizzy or lose consciousness when standing up suddenly)
• shortness of breath, sore throat, nosebleed
• abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth
• excessive passing of gas
• increased GGTP enzyme activity (liver enzyme - gamma-glutamyl transferase) in blood, increased liver enzyme activity in blood
• hives, itching, rash, hair loss, skin rash, dry skin, redness of the skin, acne, subcutaneous abscess
• increased CPK (creatine phosphokinase) activity in blood, an enzyme sometimes released from damaged muscles
• muscle cramps, joint stiffness, muscle weakness
• urinary incontinence, frequent urination, painful urination
• erectile dysfunction, ejaculation disorders, absence of menstruation or other menstrual cycle disturbances (in women), breast enlargement in men, sexual disturbances, breast pain, galactorrhea
• swelling of the face, lips, eyes or mouth, body swelling, swelling of upper or lower limbs
• increased body temperature
• change in gait
• chest pain, chest discomfort, malaise
• skin hardening
• falls

Rare (may occur in less than 1 in 1000 patients)

• eye infection
• skin inflammation caused by mites, scaly, itchy skin of the head or other body parts
• increased number of eosinophils (a type of white blood cells) in blood
• decreased number of platelets (blood cells responsible for stopping bleeding)
• tremulous head movements
• abnormal secretion of the hormone regulating urine output
• glucose in urine
• life-threatening complications of untreated diabetes
• low blood sugar levels
• excessive thirst
• lack of movement and response to stimuli in a patient who is not sleeping (catatonia)
• disorientation
• sleepwalking
• lack of emotion
• inability to achieve orgasm
• neuroleptic malignant syndrome (disorientation, decreased or loss of consciousness, high fever and severe muscle rigidity), cerebrovascular disorders including sudden interruption of blood flow to the brain (stroke or "mini" stroke), lack of response to stimuli, loss of consciousness, low level of consciousness, seizures, balance disturbances
• abnormal motor coordination
• glaucoma (increased pressure in the eyeball)
• eye movement disorders, rotational eye movements, light sensitivity, excessive tearing, redness of the eyes
• atrial fibrillation (irregular heartbeat), irregular heart rhythm
• pulmonary embolism causing chest pain and breathing difficulties. If such symptoms occur, seek immediate medical help.
• blood clots in veins, especially in the lower limbs (symptoms include swelling, pain and redness of the lower limbs). If such symptoms occur, seek immediate medical help.
• facial flushing
• breathing disturbances during sleep (sleep apnoea)
• pulmonary congestion, respiratory tract hyperaemia
• crackling sounds in the lungs, wheezing
• pancreatitis, tongue swelling, faecal incontinence, very hard stool
• intestinal obstruction
• chapped lips
• skin rash related to medicine use, skin thickening, psoriasis
• muscle fibre breakdown and muscle pain (rhabdomyolysis)
• joint swelling
• inability to pass urine
• breast discomfort, enlargement of breast glands, breast enlargement
• vaginal discharge
• priapism (prolonged erection which may require surgical intervention)
• very low body temperature, chills, feeling of thirst
• withdrawal symptoms
• abscess due to infection at injection site, deep skin infection, cyst at injection site, bruising at injection site

Frequency not known (frequency cannot be estimated from available data)

• dangerously low number of certain white blood cells responsible for fighting infections
• severe allergic reaction characterised by fever, swelling of lips, face, tongue or throat, shortness of breath, itching, skin rash, and sometimes low blood pressure
• dangerously excessive water drinking
• eating disorders related to sleep
• coma due to uncontrolled diabetes
• reduced oxygenation of various body parts (due to reduced blood flow)
• rapid, shallow breathing, aspiration pneumonia, voice disturbances
• absence of intestinal peristalsis leading to obstruction
• yellowing of the skin and eyes (jaundice)
• severe or life-threatening blistering rash with skin peeling, which may appear in the mouth, nose, eyes, genital areas and around these areas and may also spread to other body parts (Stevens-Johnson syndrome or toxic epidermal necrolysis)
• severe allergic reaction with swelling which may involve the larynx and lead to breathing difficulties
• skin depigmentation
• abnormal body posture
• in newborns whose mothers used paliperidone during pregnancy, adverse effects of the medicine and (or) withdrawal symptoms may occur, such as: irritability, slow or sustained muscle contractions, tremor, drowsiness, breathing difficulties and feeding problems
• low body temperature
• necrosis at injection site and ulcer at injection site

Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting side effects helps to provide more information on the safety of the medicine.

5. How to store Paliperidone +pharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the prefilled syringe and carton after "EXP:". The expiry date refers to the last day of the stated month.
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Paliperidone +pharma contains

• The active substance is paliperidone.

Paliperidone +pharma, 25 mg
Each pre-filled syringe contains paliperidone palmitate equivalent to 25 mg of paliperidone.
Paliperidone +pharma, 50 mg
Each pre-filled syringe contains paliperidone palmitate equivalent to 50 mg of paliperidone.
Paliperidone +pharma, 75 mg
Each pre-filled syringe contains paliperidone palmitate equivalent to 75 mg of paliperidone.
Paliperidone +pharma, 100 mg
Each pre-filled syringe contains paliperidone palmitate equivalent to 100 mg of paliperidone.
Paliperidone +pharma, 150 mg
Each pre-filled syringe contains paliperidone palmitate equivalent to 150 mg of paliperidone.
Starting treatment pack
Each pre-filled syringe contains paliperidone palmitate equivalent to 100 mg of paliperidone.
Each pre-filled syringe contains paliperidone palmitate equivalent to 150 mg of paliperidone.

• Other ingredients are: polysorbate 20, macrogol 4000, citric acid monohydrate, disodium phosphate, sodium dihydrogen phosphate monohydrate, sodium hydroxide (for pH adjustment), water for injections.

What Paliperidone +pharma looks like and contents of the pack
Paliperidone +pharma is a white or almost white injectable suspension in a pre-filled syringe (injectable suspension).
Each single pack contains:

• 1 pre-filled syringe (clear glass, type I) with a plunger, lock, and needle cap, together with a 22G 1½ inch needle with safety device and a 23G 1 inch needle with safety device. All in a cardboard box.

Each starting treatment pack contains:

• 1 pack of Paliperidone +pharma, 150 mg: 1 pre-filled syringe and 2 needles (for administration on day 1 of treatment)
• 1 pack of Paliperidone +pharma, 100 mg: 1 pre-filled syringe and 2 needles (for administration on day 8 of treatment)

Not all pack sizes may be marketed.
Marketing Authorisation Holder
+pharma arzneimittel gmbh
Hafnerstrasse 211
8054 Graz
Austria
Manufacturer/Importer
Universal Farma, S.L.
Polígono Industrial Miralcampo
C/ El Tejido 2
19200 Azuqueca de Henares – Guadalajara
Spain
Pharmascience International Limited
1st Floor Jacovides Tower
81-83 Griva Digeni Avenue
1090 Nicosia
Cyprus
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria Paliperidon Genericon 25 mg, 50 mg, 75 mg, 100 mg, 150 mg Depot-
Injektionssuspension in einer Fertigspritze
Paliperidon Genericon Starterpackung 150 mg + 100 mg Depot-Injektionssuspension in
einer Fertigspritze
Poland Paliperidone +pharma
Sweden Paliperidone Genericon
For further information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
+pharma Polska sp. z o.o.
ul. Podgórska 34
31-536 Kraków, Poland
tel.: +48 12 262 32 36
e-mail: [email protected]

Information intended solely for medical personnel or healthcare professionals and should be read in conjunction with the full product information (Summary of Product Characteristics).

The suspension for injection is intended for single use only. Before administration, inspect visually for the presence of foreign particles in the suspension. If foreign particles are observed in the prefilled syringe, do not use the medicinal product.

The package contains one prefilled syringe and two safety needles [22G 1½ inch (38.1 mm x 0.72 mm) and 23G 1 inch (25.4 mm x 0.64 mm)] for intramuscular administration. The medicinal product Paliperidone +pharma is also available in a starter pack containing two prefilled syringes (150 mg + 100 mg) and four safety needles.

1. Shake the prefilled syringe vigorously for at least 10 seconds to ensure homogeneity of the suspension.

2. Select the appropriate needle.

The first initiation dose of the medicinal product Paliperidone +pharma (150 mg) must be administered on day 1 of treatment into the DELTOID MUSCLE using the needle intended for the DELTOID MUSCLE.
The second initiation dose of the medicinal product Paliperidone +pharma (100 mg) should be administered one week later (day 8), also into the DELTOID MUSCLE using the needle intended for the DELTOID MUSCLE.
When switching from long-acting risperidone injections to the medicinal product Paliperidone +pharma, the first injection of Paliperidone +pharma (at a dose between 25 mg and 150 mg) may be administered into either the DELTOID MUSCLE or the GLUTEAL MUSCLE using the appropriate needle on the day of the next scheduled injection.
Subsequently, monthly maintenance doses may be administered into either the DELTOID MUSCLE or the GLUTEAL MUSCLE using the appropriate needle.

For intramuscular injections into the DELTOID MUSCLE in patients with body weight <90 kg, use the 1 inch, 23G (25.4 mm x 0.64 mm) needle (blue hub). If the patient's body weight is ≥90 kg, use the 1½ inch, 22G (38.1 mm x 0.72 mm) needle (grey hub).
For intramuscular injections into the GLUTEAL MUSCLE, use the 1½ inch, 22G (38.1 mm x 0.72 mm) needle (grey hub).

3. Hold the prefilled syringe with the tip pointing upward. Gently twist and remove the rubber stopper from the tip of the prefilled syringe.

4. Peel off the outer layer of the safety needle blister package. Grasp the base of the needle, not the safety mechanism. Attach the needle to the "luer" lock connector of the prefilled syringe by pressing and turning it gently clockwise.

5. Pull the protective needle shield away from the needle at the angle shown, moving it toward the body of the prefilled syringe.

6. Remove the needle cap straight off without twisting, as twisting may loosen the needle from the prefilled syringe.

7. Hold the prefilled syringe with attached needle in an upright vertical position to remove air. Expel air from the syringe by gently pressing the plunger forward.

8. Administer the entire content of the prefilled syringe slowly and deeply via intramuscular injection into the selected deltoid or gluteal muscle of the patient. Do not administer intravenously or subcutaneously.

9. After completing the injection, use either the fingers of one hand (9a) or a flat surface (9b) to activate the needle safety mechanism. A clicking sound indicates successful activation and secure locking of the needle safety system. Dispose of the prefilled syringe with attached needle appropriately.

9a

9b

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