Risperdal Consta 50 mg powder and solvent for prolonged-release suspension for intramuscular injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Risperdal Consta 50 mg powder and solvent for prolonged-release suspension for injection

risperidone

Read this 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 or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Package leaflet contents

1. What Risperdal Consta is and what it is used for
2. What you need to know before using Risperdal Consta
3. How to use Risperdal Consta
4. Possible side effects
5. Storage of Risperdal Consta
6. Contents of the pack and other information

1. What Risperdal Consta is and what it is used for

Risperdal Consta belongs to a group of medicines called "antipsychotics".

Risperdal Consta is used for the maintenance treatment of schizophrenia, which is characterized by seeing, hearing, or feeling things that are not present, believing things that are not true, or unusually feeling distrustful or confused.

Risperdal Consta is intended for patients who are currently being treated with oral antipsychotics (e.g., tablets, capsules).

Risperdal Consta can help reduce the symptoms of your illness and help prevent them from returning.

2. What you need to know before using Risperdal Consta

Do not use Risperdal Consta

• If you are allergic to risperidone or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• If you have never taken Risperdal in any form before, you must start with oral Risperdal before beginning treatment with Risperdal Consta.

Consult your doctor or pharmacist before using Risperdal Consta if:

• You have a heart condition, for example an irregular heartbeat, or if you are prone to low blood pressure, or if you are taking medicines for blood pressure. Risperdal Consta may lower blood pressure. Your dose may need to be adjusted.
• You know you have risk factors that make you prone to stroke, such as high blood pressure (hypertension), cardiovascular disorders, or cerebral circulation disorders.
• You have ever experienced involuntary movements of the tongue, mouth, or face.
• You have ever had symptoms including fever, muscle stiffness, sweating, or decreased level of consciousness (also known as Neuroleptic Malignant Syndrome).
• You have Parkinson's disease or dementia.
• You have previously had low levels of white blood cells in your blood (which may or may not have been caused by other medicines).
• You are diabetic.
• You have epilepsy.
• You are male and have ever had a prolonged or painful erection.
• You have difficulty regulating body temperature or feel excessive heat.
• You have kidney problems.
• You have liver problems.
• You have abnormally high levels of the hormone called prolactin in your blood, or if you have a tumor that may be prolactin-dependent.
• You or someone in your family has a history of blood clots, as medicines like this have been associated with blood clot formation.

If you are unsure whether any of the above applies to you, speak with your doctor or pharmacist before using Risperdal or Risperdal Consta.

Because a dangerously low number of a type of white blood cell necessary to fight infections has been observed very rarely in patients treated with Risperdal Consta, your doctor may check your white blood cell count.

Allergic reactions may rarely occur after receiving injections of Risperdal Consta, even if you have previously tolerated oral risperidone. Seek immediate medical attention if you experience hives, throat swelling, itching, or breathing difficulties, as these may be symptoms of a serious allergic reaction.

Risperdal Consta may cause weight gain. Significant weight gain may negatively affect your health. Your doctor will regularly monitor your weight.

Because diabetes mellitus has been observed or pre-existing diabetes mellitus has worsened in patients taking Risperdal, your doctor should check for signs of elevated blood sugar. In patients with pre-existing diabetes mellitus, blood sugar should be monitored regularly.

Risperdal Consta frequently increases levels of a hormone called "prolactin." This may cause adverse effects such as menstrual disorders or fertility problems in women, or breast enlargement in men (see Possible side effects). If these adverse effects occur, assessment of prolactin levels in the blood is recommended.

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 could cause eye damage. If you are considering eye surgery, make sure to inform your ophthalmologist that you are taking this medicine.

Elderly patients with dementia

Risperdal Consta is not used in elderly patients with dementia.

If you or your caregiver notice a sudden change in your mental state, or sudden onset of weakness or numbness in the face, arms, or legs—especially on one side—or slurred speech, even if temporary, seek immediate medical treatment. These may be signs of a stroke.

Patients with kidney or liver problems

Although oral risperidone has been studied, Risperdal Consta has not been studied in patients with kidney or liver problems. Risperdal Consta should be administered with caution in this patient group.

Using Risperdal Consta with other medicines

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

It is especially important that you speak with your doctor or pharmacist if you are taking any of the following:

• Medicines that act on the brain used to calm you down (benzodiazepines) or certain pain medicines (opioids), allergy medicines (some antihistamines), as risperidone may increase the sedative effect of all these.
• Medicines capable of altering the electrical activity of your heart, such as those used for malaria, heart rhythm disorders, allergies (antihistamines), some antidepressants, or other medicines for mental disorders.
• Medicines that may cause a decrease in heartbeats.
• Medicines that may cause low potassium levels in the blood (such as certain diuretics).
• Medicines for Parkinson's disease (such as levodopa).
• Medicines that increase central nervous system activity (psychostimulants, such as methylphenidate).
• Medicines for high blood pressure. Risperdal Consta may lower blood pressure.
• Diuretics used for heart problems or to treat swelling in certain body parts due to fluid retention (such as furosemide or chlorothiazide). Risperdal Consta, taken alone or with furosemide, may increase the risk of stroke or death in elderly patients with dementia.

The following medicines may reduce the effect of risperidone:

• Rifampicin (a medicine used to treat certain infections).
• Carbamazepine, phenytoin (medicines used to treat epilepsy).
• Phenobarbital.

If you start or stop taking these medicines, you may require a different dose of risperidone.

The following medicines may increase the effect of risperidone:

• Quinidine (a medicine used to treat certain types of heart problems).
• Antidepressants such as paroxetine, fluoxetine, tricyclic antidepressants.
• Medicines known as beta-blockers (used to treat high blood pressure).
• Phenothiazines (such as medicines used to treat psychosis or to calm).
• Cimetidine, ranitidine (medicines used to treat stomach acid).
• Itraconazole and ketoconazole (medicines used to treat fungal infections).
• Some medicines used to treat HIV/AIDS, such as ritonavir.
• Verapamil, a medicine used to treat high blood pressure and/or abnormal heart rhythm.
• Sertraline and fluvoxamine, medicines used to treat depression and other psychiatric disorders.

If you start or stop taking these medicines, you may require a different dose of risperidone.

If you are unsure whether any of the above applies to you, speak with your doctor or pharmacist before using Risperdal Consta.

Use of Risperdal Consta with food, drinks, and alcohol

You should avoid consuming alcohol while using Risperdal Consta.

Pregnancy, breastfeeding, and fertility

• 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. Your doctor will decide whether you can use it.
• The following symptoms may occur in newborn babies whose mothers have been treated with Risperdal Consta during the last trimester of pregnancy (last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, restlessness, breathing difficulties, and feeding problems. If your baby develops any of these symptoms, contact your doctor.
• Risperdal Consta may increase levels of a hormone called "prolactin," which could affect your fertility (see Possible side effects).

Driving and using machines

Dizziness, fatigue, and vision problems have been observed during treatment with Risperdal Consta. Do not drive or operate tools or machinery without first consulting your doctor.

Risperdal Consta contains sodium

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

3. How to use Risperdal Consta

Follow exactly the instructions for administration of this medicine given by your doctor. If in doubt, consult your doctor or pharmacist again.

Risperdal Consta is administered by intramuscular injection into the arm or buttock every two weeks by a healthcare professional. Injections should alternate between the left and right sides and must not be given intravenously.

Recommended dose is as follows:

Adults

Initial dose

If your daily oral risperidone dose (e.g., tablets) was 4 milligrams or less during the previous two weeks, your starting dose should be 25 milligrams of Risperdal Consta.

If your daily oral risperidone dose (e.g., tablets) was more than 4 milligrams during the previous two weeks, you may be given 37.5 milligrams of Risperdal Consta as the starting dose.

If you are currently being treated with another oral antipsychotic other than risperidone, your starting dose of Risperdal Consta will depend on your current treatment. Your doctor will choose either Risperdal Consta 25 mg or 37.5 mg.

Your doctor will decide whether this dose of Risperdal Consta is suitable for you.

Maintenance dose

• The usual dose is a 25-milligram injection every two weeks.
• A higher dose of 37.5 or 50 mg may be required. Your doctor will decide which dose of Risperdal Consta is most appropriate for you.
• Your doctor may prescribe oral Risperdal during the first three weeks after the first injection.

If you use more Risperdal Consta than you should

• People who have used more Risperdal Consta than they should have experienced the following symptoms: drowsiness, fatigue, abnormal body movements, difficulty standing and walking, dizziness due to lowered blood pressure, and abnormal heartbeats. Cases of abnormalities in the heart's electrical conduction and seizures have been reported.
• Contact your doctor, pharmacist, or call the Toxicology Information Service immediately at telephone number 91.562.04.20, indicating the medicine and the amount taken.

It is recommended to carry the medicine packaging and package leaflet to the healthcare professional.

If you stop using Risperdal Consta

The effects of this medicine will be lost. You should not stop using this medicine unless instructed by your doctor, as your symptoms may return. Make sure you receive your injections every two weeks. If you are unable to attend your appointments, contact your doctor immediately to schedule another appointment.

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

Use in children and adolescents

Risperdal Consta must not be given to children and adolescents under 18 years of age.

4. Possible adverse effects

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

Immediately inform your doctor if you experience any of the following uncommon adverse effects (may affect up to 1 in 100 patients):

• You have dementia and experience a sudden change in your mental state or sudden weakness or numbness of the face, arms or legs, especially on one side, or have difficulty speaking even for a short period of time. These may be signs of a stroke.
• You develop tardive dyskinesia (involuntary spasms or twitching movements of 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. Discontinuation of Risperdal Consta may be necessary.

Immediately inform your doctor if you experience any of the following rare adverse effects (may affect up to 1 in 1,000 patients):

• 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 immediate medical advice.
• You develop fever, muscle stiffness, sweating, or decreased level of consciousness (a condition known as "Neuroleptic Malignant Syndrome"). Immediate medical treatment may be required.
• You are a man and experience a prolonged or painful erection. This is known as priapism. Immediate medical treatment may be required.
• You experience a severe allergic reaction characterized by fever, swelling of the mouth, face, lips or tongue, difficulty breathing, itching, skin rash or low blood pressure. Even if you previously tolerated oral risperidone, severe allergic reactions may rarely occur after receiving Risperdal Consta injections.

Other adverse effects may also occur:

Very common adverse effects (may affect more than 1 in 10 people)

• Symptoms of the common cold
• Difficulty falling or staying asleep
• Depression, anxiety
• Parkinsonism: This condition may include: slow or impaired movement, sensation of muscle stiffness or tightness (resulting in jerky movements), and sometimes a "freezing" sensation in movement that later resumes. Other signs of parkinsonism include shuffling gait, resting tremor, increased saliva and/or drooling, and reduced facial expression.
• Headache.

Common adverse effects (may affect up to 1 in 10 people)

• Pneumonia, chest infection (bronchitis), sinusitis
• Urinary tract infection, feeling as if you have the flu, anemia
• Increased levels of a hormone called "prolactin" detected in blood tests (which may or may not cause symptoms). Symptoms of elevated prolactin rarely occur and in men may include breast enlargement, difficulty achieving or maintaining erections, decreased sexual desire or other sexual dysfunctions. In women, symptoms may include breast discomfort, milk secretion from the breasts, missed menstrual periods or other menstrual cycle problems or fertility issues
• Increased blood sugar, weight gain, increased appetite, weight loss, decreased appetite
• Sleep disturbances, irritability, decreased sexual desire, restlessness, feeling drowsy or less alert
• Dystonia: A condition involving involuntary, slow or sustained muscle contractions. Although any part of the body may be affected (and may lead to abnormal postures), dystonia frequently affects facial muscles, including abnormal eye, mouth, tongue or jaw movements
• Dizziness
• Dyskinesia: A condition involving involuntary muscle movements, which may include repetitive, spasmodic or twisting movements or spasms
• Tremor (shakiness)
• Blurred vision
• Rapid heartbeat
• Low blood pressure, chest pain, increased blood pressure
• Shortness of breath, sore throat, cough, nasal congestion
• Abdominal pain, abdominal discomfort, vomiting, nausea, stomach or intestinal infection, constipation, diarrhea, indigestion, dry mouth, toothache
• Skin rash
• Muscle spasms, bone or muscle pain, back pain, joint pain
• Urinary incontinence (loss of bladder control)
• Erectile dysfunction
• Absence of menstrual periods
• Milk secretion from the breasts
• Swelling of the body, arms or legs, fever, weakness, fatigue (tiredness)
• Pain
• Injection site reaction, including itching, pain or swelling
• Increased liver transaminases in blood, increased GGT (a liver enzyme called gamma-glutamyltransferase) in blood
• Falls.

Uncommon adverse effects (may affect up to 1 in 100 people)

• Respiratory tract infection, bladder infection, ear infection, eye infection, tonsillitis, fungal nail infection, skin infection, localized infection in a single skin area or body part, viral infection, skin inflammation caused by mites, subcutaneous abscess

• Decreased number of white blood cells, decreased platelets (blood cells that help stop bleeding), decreased red blood cells

• Allergic reaction

• Sugar in urine, diabetes or worsening of diabetes

• Loss of appetite leading to malnutrition and reduced body weight

• Increased triglycerides in blood (fat), increased blood cholesterol

• Euphoria (mania), confusion, inability to achieve orgasm, nervousness, nightmares

• Loss of consciousness, seizures (epileptic fits), fainting

• Restlessness causing body movements, balance disorder, abnormal coordination, dizziness upon standing, attention disturbance, speech problems, loss or alteration of taste, decreased skin sensitivity to pain or touch, tingling, prickling or numbness of the skin

• Eye infection or "red eye", dry eyes, increased tearing, eye redness

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

• Atrial fibrillation (abnormal heart rhythm), interruption of conduction between upper and lower parts of the heart, abnormal electrical activity of the heart, QT interval prolongation on the heart, slow heartbeat, abnormal electrical conduction of the heart (electrocardiogram or ECG), sensation of fluttering or pounding in the chest (palpitations)

• Low blood pressure upon standing (as a result, some people taking Risperdal Consta may feel weakness, dizziness or loss of consciousness when standing up or sitting down suddenly)

• Rapid, shallow breathing, respiratory congestion, gasping, nosebleeds

• Fecal incontinence, difficulty swallowing, excess gas or flatulence

• Itching, hair loss, eczema, dry skin, skin redness, skin discoloration, acne, scaly or itchy scalp or skin

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

• Joint stiffness, joint swelling, muscle weakness, neck pain

• Frequent urination, inability to urinate, painful urination

• Ejaculation disorders, delayed menstruation, absence of menstrual periods or other menstrual cycle problems (in women), breast development in men, sexual dysfunction, breast pain, breast discomfort, vaginal discharge

• Swelling of the face, mouth, eyes or lips

• Chills, increased body temperature

• Change in walking pattern

• Thirst sensation, feeling unwell, chest discomfort, feeling "under the weather"

• Skin hardening

• Increased liver enzymes in blood

• Pain due to the procedure.

Rare adverse effects (may affect up to 1 in 1,000 people)

• Decrease in a type of white blood cells that help fight infections
• Inappropriate secretion of a hormone that controls urine volume
• Low blood sugar level
• Excessive water intake
• Sleepwalking
• Sleep-related eating disorder
• Lack of movement or response while awake (catatonia)
• Absence of emotions
• Decreased level of consciousness
• Head agitation
• Eye movement problems, eye rolling, light sensitivity of the eyes
• Eye problems during cataract surgery. During cataract surgery, a condition called intraoperative floppy iris syndrome (IFIS) may occur if you are taking or have taken Risperdal Consta. If you need cataract surgery, make sure to inform your ophthalmologist if you are taking or have taken this medicine
• Irregular heartbeat
• Dangerously low number of a type of white blood cells needed to fight infections in the blood, increased eosinophils (a type of white blood cell) in blood
• Breathing difficulty during sleep (sleep apnea)
• Pneumonia caused by aspiration of food, lung congestion, crackling lung sounds, voice disorder, respiratory tract disorder
• Pancreatitis, intestinal obstruction
• Very hard stools
• Drug-related skin rash
• Hives (or "urticaria"), skin thickening, dandruff, skin disorder, skin lesion
• Muscle fiber breakdown and muscle pain (rhabdomyolysis)
• Abnormal posture
• Breast enlargement, milk secretion from the breasts
• Decreased body temperature, feeling unwell
• Yellowing of the skin and eyes (jaundice)
• Dangerously excessive water intake
• Increased insulin (a hormone that controls blood sugar levels) in blood
• Problems with blood vessels in the brain
• No response to stimuli
• Coma due to uncontrolled diabetes
• Sudden loss of vision or blindness
• Glaucoma (increased pressure in the eyeball), crusts on the eyelid margin
• Flushing, tongue swelling
• Cracked lips
• Enlargement of mammary glands
• Decreased body temperature, coldness in arms and legs
• Medication withdrawal symptoms.

Very rare adverse effects (may affect up to 1 in 10,000 people)

• Life-threatening complications of uncontrolled diabetes
• Severe allergic reaction with swelling, which may affect the throat causing breathing difficulty
• Lack of movement in intestinal muscles leading to obstruction.

Frequency not known: cannot be estimated from available data

• Severe or life-threatening blistering and peeling skin rash, which may start around the mouth, nose, eyes, genitals and spread to other body areas (Stevens-Johnson Syndrome or toxic epidermal necrolysis).

The following adverse effect has been reported with the use of another medicine called paliperidone, which is very similar to risperidone; therefore, it may also occur with Risperdal Consta: rapid heartbeat upon standing.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Risperdal Consta

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.

Store in a refrigerator (between 2°C and 8°C). If refrigeration is not available, the container may be stored below 25°C for a maximum of 7 days before administration. Administer within 6 hours after reconstitution (if stored at 25°C or lower).

Keep in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Risperdal Consta

The active substance is risperidone.

Each Risperdal Consta powder and solvent for prolonged-release injection suspension contains 50 milligrams of risperidone.

The other components are:

Powder

poly-(d,l-lactide-co-glycolide).

Solvent (solution):

Polysorbate 20, Sodium carboxymethylcellulose, Disodium hydrogen phosphate dihydrate, Anhydrous citric acid, Sodium chloride, Sodium hydroxide, Water for injection.

Appearance of Risperdal Consta and contents of the pack

• One small vial containing the powder (this powder contains the active substance, risperidone). One pre-filled syringe containing 2 ml of clear, colourless liquid which is added to the powder to form a prolonged-release suspension for injection.
• One vial adapter for reconstitution.
• Two Terumo SurGuard® 3 needles for intramuscular injection (one 21G UTW safety needle, 1 inch (0.8 mm × 25 mm) with needle safety shield for administration into the deltoid, and one 20G TW safety needle, 2 inches (0.9 mm × 51 mm) with needle safety shield for administration into the gluteal muscle).

Risperdal Consta is available in packs containing 1 to 5 unit packs.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Janssen-Cilag, S.A.

Paseo del Club Deportivo 1, Edificio 16

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Janssen Pharmaceutica, N.V.

Turnhoutseweg, 30

B-2340, Beerse

Belgium

This medicinal product has been authorised in the EEA Member States under the following names:

Austria: RISPERDAL CONSTA

Belgium: RISPERDAL CONSTA

Cyprus: RISPERDAL CONSTA

Czech Republic: RISPERDAL CONSTA

Denmark: RISPERDAL CONSTA

Estonia: RISPOLEPT CONSTA

Finland: RISPERDAL CONSTA

France: RISPERDAL CONSTA LP

Germany: RISPERDAL CONSTA 25mg, 37.5mg, 50mg

Greece: RISPERDAL CONSTA

Hungary: RISPERDAL CONSTA

Iceland: RISPERDAL CONSTA

Ireland: RISPERDAL CONSTA

Italy: RISPERDAL

Lithuania: RISPOLEPT CONSTA

Latvia: RISPOLEPT CONSTA

Liechtenstein: RISPERDAL CONSTA

Luxembourg: RISPERDAL CONSTA

Malta: RISPERDAL CONSTA

Netherlands: RISPERDAL CONSTA

Norway: RISPERDAL CONSTA

Poland: RISPOLEPT CONSTA

Portugal: RISPERDAL CONSTA

Romania: RISPOLEPT CONSTA

Slovakia: RISPERDAL CONSTA

Slovenia: RISPERDAL CONSTA

Spain: RISPERDAL CONSTA

Sweden: RISPERDAL CONSTA

United Kingdom: RISPERDAL CONSTA

This leaflet was last revised in: April 2021.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es

IMPORTANT INFORMATION FOR HEALTHCARE PROFESSIONALS

Important information

RISPERDAL CONSTA requires careful attention at each step of the "Instructions for Use" to help ensure successful administration.

Use of supplied components

The components in the pack are specifically designed for use with RISPERDAL CONSTA. RISPERDAL CONSTA must only be reconstituted with the solvent provided in the pack.

Do not substitute ANY of the pack components.

Do not store the suspension after reconstitution

Administer the dose as soon as possible after reconstitution to avoid sedimentation.

Correct dosing

The entire contents of the vial must be administered to ensure the correct dose of RISPERDAL CONSTA is delivered.

Do not reuse. Medical devices require materials with specific characteristics to function properly. These characteristics have been verified for single use only. Any attempt to reprocess the device for subsequent reuse may adversely affect the device's integrity or lead to impaired performance.

Pack components

Step 1	Assemble the components
Remove the dose container from the refrigerator	Attach the vial adapter to the vial
Wait 30 minutes Remove the dose container from the refrigerator and allow it to reach room temperature for at least 30 minutes before reconstitution. Do not heat by any other means.	Remove the vial cap Remove the colored cap from the vial. Clean the top of the grey stopper with an alcohol swab. Allow it to air dry. Do not remove the grey rubber stopper.	Prepare the vial adapter Hold the sterile blister pack as shown. Peel off the paper backing. Do not remove the vial adapter from the blister pack. Do not touch the tip of the piercing pin at any time. This may cause contamination.	Attach the vial adapter to the vial Place the vial on a hard surface and hold it by the base. Center the vial adapter over the grey rubber stopper. Press the vial adapter straight down until it snaps securely into place on the vial. Do not place the vial adapter at an angle, as this may result in loss of solvent during transfer to the vial.

Attach the pre-filled syringe to the vial adapter

Remove the sterile blister Keep the vial upright to prevent spillage. Hold the base of the vial and pull off the sterile blister. Do not shake. Do not touch the exposed, open luer (cone) on the vial adapter. This may result in contamination.	Use the correct gripping area Hold the syringe by the white ring on the tip. Do not hold the syringe by the glass during assembly.	Remove the cap Holding the white ring, break off the white cap. Do not twist or cut the white cap. Do not touch the syringe tip. This may result in contamination. The broken cap can be discarded.	Attach the syringe to the vial adapter Hold the vial adapter by the rim to keep it steady. Hold the syringe by the white ring and insert the tip into the luer (cone) opening of the vial adapter. Do not hold the syringe by the glass barrel. This may cause the white ring to loosen or detach. Connect the syringe to the vial adapter with a firm clockwise twisting motion until tight. Do not over-tighten. Over-tightening may cause the syringe tip to break.
Step 2	Reconstitute the microspheres
Inject solvent Inject the entire amount of solvent from the syringe into the vial.	Suspend the microspheres in the solvent Continue pressing down on the plunger with your thumb and shake vigorously, as shown, for at least 10 seconds. Inspect the suspension. When properly mixed, the suspension will appear uniform, thick, and milky in color. The microspheres will be visible in the liquid. Proceed immediately to the next step to prevent sedimentation of the suspension.	Transfer the suspension to the syringe Completely invert the vial. Slowly pull the plunger rod down to draw all the contents from the vial into the syringe.	Remove the vial adapter Hold the syringe by the white ring and unscrew it from the vial adapter. Cut the vial label along the perforated area. Place the detached label on the syringe for identification. Dispose of both the vial and the vial adapter properly (see section 5 of this leaflet).

Step 3	Attach the needle
Select the appropriate needle Select the needle according to the injection site (gluteal or deltoid).	Attach the needle Open the blister pack at the partially peeled area and use it to hold the base of the needle, as shown. Holding the white ring of the syringe, attach the syringe to the luer (cone) of the needle with a firm clockwise rotating motion until securely fastened. Do not touch the opening of the luer (cone) of the needle. This may cause contamination.	Resuspend the microspheres Completely remove the blister pack. Just before injection, shake the syringe vigorously again in case any sedimentation has occurred.
Step 4	Inject the dose
Remove the transparent needle cap Move the needle safety device toward the syringe as shown. Then, hold the white ring of the syringe and carefully remove the transparent needle cap. Do not twist the transparent needle cap, as this may dislodge the luer (cone) connection.	Remove air bubbles Hold the syringe upright and gently tap it to allow air bubbles to rise to the top. Slowly and carefully press the plunger rod to expel the air.	Inject Immediately inject the entire contents of the syringe intramuscularly (IM) into the patient's gluteal or deltoid muscle. The gluteal injection should be administered into the upper outer quadrant of the buttock. Do not administer intravenously.	Protect the needle in the safety device Using one hand, place the needle safety device at a 45-degree angle onto a flat, hard surface. Press down firmly and quickly until the needle is completely enclosed within the safety device. To avoid needlestick injury: Do not use both hands. Do not disengage or deliberately misuse the needle safety device. Do not attempt to straighten or reattach the safety device if the needle is bent or damaged.	Dispose of needles properly Ensure that the needle safety device is fully engaged. Dispose of it in a sharps container. Also dispose of the needle provided in the dose packaging that was not used (see section 5 of this leaflet).