Pegasys

Package leaflet: Information for the user

Pegasys 180 micrograms solution for injection

peginterferon alfa-2a
Please read 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Pegasys is and what it is used for

Pegasys contains the active substance peginterferon alfa-2a, a long-acting interferon.
Interferon is a protein that modifies the immune system’s response (the body's defence system), helping it fight infections and serious diseases. Pegasys is used for the treatment of chronic hepatitis B or C in adults. It is also used for the treatment of chronic hepatitis B in children and adolescents aged 3 years and above, and for chronic hepatitis C in children and adolescents aged 5 years and above who have not been previously treated. Both chronic hepatitis B and C are viral infections of the liver.
Chronic hepatitis B: Pegasys is usually used alone.
Chronic hepatitis C: Pegasys is used in combination with other medicines for the treatment of chronic hepatitis C (CHC).
Also consult the package leaflets of any other medicines used in combination with Pegasys.

2. What you need to know before using Pegasys

Do not use Pegasys

• if you are allergic to peginterferon alfa-2a, to any interferon, or to any of the other ingredients of this medicine (listed in section 6);
• if you have ever had a heart attack or have been hospitalized due to severe chest pain in the last 6 months;
• if you have so-called autoimmune hepatitis;
• if you have advanced liver disease and your liver is not functioning properly (e.g. your skin has turned yellow);
• if the patient is a child under 3 years of age;
• if the patient is a child who has previously had severe psychiatric disorders, such as severe depression or suicidal thoughts;
• if you have been infected with both the hepatitis C virus and the human immunodeficiency virus (HIV) and your liver is not functioning properly (e.g. your skin has turned yellow);
• if you are being treated with telbivudine, a medicine used to treat hepatitis B virus infection (see section “Other medicines and Pegasys”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pegasys:

• if you have had a serious mental or neurological disorder;
• if you have had depression or symptoms associated with depression (e.g. feelings of sadness, hopelessness, etc.);
• if you are an adult with a history of substance abuse (e.g. alcohol or drugs);
• if you have psoriasis, as this condition may worsen during treatment with Pegasys;
• if you have a liver problem other than hepatitis B or C;
• if you have diabetes or high blood pressure, your doctor may recommend an eye examination;
• if you know you suffer from VKH syndrome;
• if you have a thyroid disorder that is not well controlled with medication;
• if you have had anemia;
• if you have undergone an organ transplant (liver or kidney) or are scheduled to undergo one in the near future;
• if you also have an HIV (human immunodeficiency virus) infection and are being treated with anti-HIV drugs;
• if you previously discontinued hepatitis C therapy due to anemia or low blood cell counts.

When starting treatment with Pegasys, inform your doctor, nurse, or pharmacist:

• if you develop symptoms associated with depression (e.g. feelings of sadness, hopelessness, etc.) (see section 4).
• if you notice any changes in vision.
• if you develop symptoms of cold or other respiratory infections (such as cough, fever, or difficulty breathing).
• if you suspect you have an infection (e.g. pneumonia), as you may temporarily have an increased risk of infections while taking Pegasys.
• if you develop signs of bleeding or unusual bruising, contact your doctor immediately.
• if you develop signs of a severe allergic reaction (such as difficulty breathing, wheezing, or hives) while taking the medicine, seek urgent medical attention.
• if you develop symptoms of Vogt-Koyanagi-Harada syndrome; a group of disorders including neck stiffness, headache, loss of skin and hair pigmentation, vision problems (such as blurred vision), and/or hearing changes (such as ringing in the ears).

During treatment, your doctor will perform regular blood tests to monitor changes in white blood cells (cells that fight infections), red blood cells (cells that carry oxygen), platelets (cells involved in blood clotting), liver function, blood glucose (blood sugar levels), or other laboratory values.
Dental and gum disorders, which may lead to tooth loss, have been reported in patients treated with Pegasys in combination with ribavirin. In addition, dry mouth may have a harmful effect on teeth and oral mucosa during prolonged treatment with Pegasys and ribavirin. You should brush your teeth thoroughly twice daily and attend regular dental check-ups. Furthermore, some patients may experience vomiting. In such cases, make sure to rinse your mouth thoroughly after vomiting.

Children and adolescents
Pegasys may only be used in children and adolescents aged 5 years and older with chronic hepatitis C, or in children and adolescents aged 3 years and older with chronic hepatitis B. Pegasys must not be administered to children under 3 years of age because it contains benzyl alcohol and may cause toxic or allergic reactions in these children.

• If the child has a psychiatric disorder, or has had one in the past, discuss this with the doctor, who will monitor the child for signs or symptoms of depression (see section 4).
• During treatment with Pegasys, the child may experience slowed growth and development (see section 4).

Other medicines and Pegasys
Do not use Pegasys if you are taking telbivudine (see section “Do not use Pegasys”) because the combination of these medicines increases the risk of developing peripheral neuropathy (numbness, tingling, and/or burning sensations in the arms and/or legs). Therefore, the combination of Pegasys with telbivudine is contraindicated. Inform your doctor or pharmacist if you are being treated with telbivudine.
Inform your doctor if you are taking medicines for asthma, as the dose of your asthma medicine may need to be adjusted.
If you are also infected with HIV: inform your doctor if you are receiving anti-HIV therapy. Lactic acidosis and worsening liver function are adverse effects associated with highly active antiretroviral therapy (HAART), a treatment for HIV. If you are receiving HAART, adding Pegasys plus ribavirin may increase the risk of lactic acidosis or liver failure. Your doctor will monitor you for signs and symptoms of these conditions. Patients treated with zidovudine in combination with ribavirin and alpha interferons have an increased risk of developing anemia. Patients treated with azathioprine in combination with ribavirin and peginterferon have an increased risk of developing severe blood disorders. Make sure to also read the package leaflet of ribavirin.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
When Pegasys is used in combination with ribavirin, both male and female patients must take special precautions during sexual activity if there is any possibility of pregnancy, as ribavirin can be highly harmful to the fetus:

• if you are a woman of childbearing potential taking Pegasys in combination with ribavirin, you must have a negative pregnancy test before starting treatment, every month during treatment, and for 4 months after completing treatment. You must use an effective contraceptive method during treatment and for 4 months after completing treatment. This can be discussed with your doctor;
• if you are a man taking Pegasys in combination with ribavirin, avoid sexual intercourse with pregnant women unless you use a condom. This reduces the likelihood of ribavirin being transferred to the woman’s body. If your female partner is not currently pregnant but is of childbearing potential, she must have a pregnancy test every month during treatment and for 7 months after completing treatment. You and your partner must use an effective contraceptive method during treatment and for 7 months after completing treatment. This can be discussed with your doctor.

Consult your doctor or pharmacist before taking any medicine. It is not known whether this product passes into breast milk. Therefore, do not breastfeed while taking Pegasys. Regarding combination therapy with ribavirin, consider the information contained in the package leaflets of medicines containing ribavirin.
Also consult the package leaflets of any other medicines used in combination with Pegasys.

Driving and using machines
If you feel drowsy, tired, or confused while taking Pegasys, do not drive or operate machinery.

Pegasys contains benzyl alcohol, polysorbate 80, and sodium
This medicine contains 10 mg of benzyl alcohol per vial, equivalent to 10 mg/mL.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with a risk of serious adverse effects, including breathing problems (gasping syndrome), in young children.
Pegasys must not be given to premature infants, newborns, or children under 3 years of age.
Consult your doctor or pharmacist if you are pregnant or breastfeeding, or if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).
This medicine contains 0.05 mg of polysorbate 80 per vial, equivalent to 0.05 mg/mL.
Polysorbates may cause allergic reactions. Inform your doctor if you or your child has known allergies.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to use Pegasys

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Dosage of Pegasys
Your doctor will determine the exact dose of Pegasys and will tell you how often to take it. If
necessary, the dose may be adjusted during treatment. Do not exceed the recommended dose.
Pegasys is used alone only if, for any reason, you cannot take ribavirin.
Pegasys, used alone or in combination with ribavirin, is generally administered at a dose of 180 micrograms once weekly.
The duration of combination therapy varies from 4 to 18 months, depending on the characteristics of the virus infecting you, your response to treatment, and whether you have been previously treated.
Discuss this with your doctor and follow the recommended treatment duration.
Pegasys injection is normally given at bedtime.
Use in children and adolescents
Your doctor will determine the exact dose of Pegasys for the child and will tell you how often to administer it. The usual dose of Pegasys is based on the child's height and weight. If necessary, the dose may be adjusted during treatment. The use of pre-filled Pegasys syringes is recommended for children and adolescents, as they allow dose adjustment. Do not exceed the recommended doses.
The duration of combination therapy in children with chronic hepatitis C varies from 6 to 12 months and depends on the type of virus causing the child’s infection and the response to therapy.
In chronic hepatitis B, the duration of treatment with Pegasys is 48 weeks. Check with your doctor and follow the recommended treatment duration. Pegasys injection is usually given before going to bed.
Pegasys is intended for subcutaneous use (under the skin). Therefore, Pegasys is injected with a short needle into the subcutaneous fatty tissue of the abdomen or thigh. If you are administering the injection yourself, you will be trained on how to self-inject. Detailed instructions are provided at the end of this leaflet (see section “How to administer Pegasys”).
Use Pegasys exactly as shown to you by your doctor, for the duration prescribed by your doctor.
If you feel that the effect of Pegasys is too strong or too weak, consult your doctor or pharmacist.
Combination therapy with ribavirin in chronic hepatitis C
If you are receiving combination therapy with Pegasys and ribavirin, follow the dosing regimen recommended by your doctor.
Combination therapy with other medicines in chronic hepatitis C
If you are receiving combination therapy with Pegasys, follow the dosing regimen recommended by your doctor and also consult the package leaflets of any other medicines used in combination with Pegasys.
If you use more Pegasys than you should
Contact your doctor or pharmacist as soon as possible.
If you forget to take Pegasys
If you realize you have missed an injection 1 or 2 days after the scheduled time, inject the recommended dose as soon as possible. Then take the next dose according to the recommended schedule.
If you realize you have missed an injection 3 to 5 days after the scheduled time, take the recommended dose as soon as possible. Then take subsequent doses at 5-day intervals until you return to your regular weekly day.
For example: You normally inject Pegasys on Monday. On Friday, you remember that you missed the Monday injection (4 days late). You should inject the missed dose immediately (on Friday) and then administer the next injection on Wednesday (5 days after Friday). The following injection will be on Monday, 5 days after Wednesday. You are now back on your regular schedule and should continue injections every Monday.
If you realize you have missed an injection 6 days after the scheduled time, wait and inject the dose on the next scheduled day.
Contact your doctor or pharmacist if you need help managing a missed dose of Pegasys.
Do not take a double dose to make up for a forgotten dose.
If you have any questions about the use of Pegasys, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Some patients become depressed during treatment with Pegasys, either alone or in combination with ribavirin, and in some cases suicidal thoughts or aggressive behaviour (sometimes directed towards other people, such as thoughts of threatening the lives of others) may occur. Some patients have died by suicide. Seek urgent medical help if you notice signs of depression, suicidal thoughts or changes in your behaviour. Ask a family member or friend to help you promptly identify any signs of depression or changes in your behaviour.

Growth and development (children and adolescents):
Some children and adolescents treated with Pegasys for chronic hepatitis B for 48 weeks did not grow or gain weight as expected for their age. It is not yet known whether they will reach the expected adult height and weight after completion of therapy.
With up to one year of treatment with Pegasys in combination with ribavirin in children and adolescents with chronic hepatitis C, growth and weight gain may be less than expected. Although many children reach the expected height within two years after completing treatment, and most of the remaining children within six years after treatment ends, treatment with Pegasys may still affect final adult height.

Inform your doctor immediately if you notice any of the following side effects: severe chest pain; persistent cough; irregular heartbeat; difficulty breathing; confusion; depression; severe stomach ache; blood in the stool (or black, tarry stools); severe nosebleeds; fever or chills; vision problems. These side effects may be serious and you may need urgent medical attention.

Very common side effects with the combination of Pegasys and ribavirine (may affect more than 1 in 10 people) are:
Metabolism and nutrition disorders: loss of appetite
Psychiatric and nervous system disorders: depression (feeling down, feeling uncomfortable with oneself or feeling hopeless), anxiety, inability to sleep, headache, difficulty concentrating and dizziness
Respiratory disorders: cough, shortness of breath
Gastrointestinal disorders: diarrhoea, nausea, abdominal pain
Skin disorders: hair loss and skin reactions (including itching, dermatitis and dry skin)
Musculoskeletal disorders: joint and muscle pain
General disorders: fever, weakness, fatigue, tremors and chills, pain, irritation at the injection site, irritability (mood swings).

Common side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 10 people) are:
Infections: fungal, viral and bacterial infections. Upper respiratory tract infections, bronchitis, oral fungal infections (fungal infections), and herpes (a common recurring viral infection affecting the lips and mouth)
Blood disorders: decreased platelet count (affecting blood clotting), anaemia (decrease in red blood cells) and swollen lymph glands
Endocrine disorders: increased or decreased thyroid function
Psychiatric and nervous system disorders: mood changes, aggression, irritability, decreased sexual desire, poor memory, fainting, muscle weakness, migraine, numbness, tingling, burning sensation, tremor, taste disturbances, nightmares, drowsiness
Eye disorders: blurred vision, eye pain, eye inflammation and dry eyes
Ear disorders: ear pain
Cardiac and vascular disorders: rapid heartbeat, palpitations, swelling of extremities, hot flushes
Respiratory disorders: shortness of breath during activity, nosebleeds, inflammation of the nose and throat, nasal and sinus infections (infections of the air-filled spaces in the bones of the head and face), runny nose, sore throat
Gastrointestinal disorders: vomiting, indigestion, difficulty swallowing, mouth ulcers, bleeding gums, inflammation of the tongue and mouth, flatulence (excessive air or gas), dry mouth and weight loss
Skin disorders: skin rash, increased sweating, psoriasis, urticaria, eczema, photosensitivity, night sweats
Musculoskeletal disorders: back pain, joint inflammation, muscle weakness, bone pain, neck pain, muscle pain, muscle cramps
Reproductive system disorders: impotence (inability to maintain an erection)
General disorders: chest pain, flu-like illness, malaise (feeling unwell), hot flushes, thirst.

Uncommon side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 100 people) are:
Infections: lung infection, skin infections
Benign and malignant tumours: liver tumour
Immune system disorders: sarcoidosis (areas of inflamed tissue developing throughout the body), thyroid inflammation
Endocrine disorders: diabetes (high blood sugar levels)
Metabolism and nutrition disorders: dehydration
Psychiatric and nervous system disorders: suicidal thoughts, hallucinations, peripheral neuropathy (nerve disorder affecting the extremities)
Eye disorders: retinal haemorrhage (bleeding at the back of the eye)
Ear disorders: hearing loss
Cardiac and vascular disorders: high blood pressure
Respiratory disorders: wheezing
Gastrointestinal disorders: gastrointestinal bleeding
Liver disorders: impaired liver function.

Rare side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 1,000 people) are:
Infections: heart infection, outer ear infection
Blood disorders: severe reduction in red blood cells, white blood cells and platelets
Immune system disorders: severe allergic reactions, systemic lupus erythematosus (a disease in which the body attacks its own cells), rheumatoid arthritis (an autoimmune disease)
Endocrine disorders: diabetic ketoacidosis, a complication of uncontrolled diabetes
Psychiatric and nervous system disorders: suicide, psychotic disorders (severe personality disturbances and deterioration of normal social functioning), coma (a deep and prolonged state of unconsciousness), seizures, facial paralysis (weakness of facial muscles)
Eye disorders: inflammation and swelling of the optic nerve, retinal inflammation, corneal ulceration
Cardiac disorders: heart attack, heart failure, chest pain, rapid heartbeat, heart rhythm disturbances or inflammation of the lining of the heart and heart muscle
Vascular disorders: cerebral haemorrhage and blood vessel inflammation
Respiratory disorders: interstitial pneumonia (lung inflammation including fatal outcomes), blood clots in the lungs
Gastrointestinal disorders: stomach ulcer, pancreatitis (inflammation of the pancreas)
Liver disorders: liver failure, bile duct inflammation, fatty liver
Musculoskeletal disorders: muscle inflammation
Renal disorders: kidney failure
Injury or poisoning: overdose of substances.

Very rare side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 10,000 people) are:
Blood disorders: aplastic anaemia (failure of the bone marrow to produce red blood cells, white blood cells and platelets)
Immune system disorders: idiopathic or thrombotic thrombocytopenic purpura (increased bruising, bleeding, reduced platelet count, anaemia and extreme weakness)
Eye disorders: loss of vision
Skin disorders: toxic epidermal necrolysis/Stevens-Johnson syndrome/erythema multiforme (a range of skin rashes with varying severity, including death, which may be associated with blisters in the mouth, nose, eyes and other mucous membranes and peeling of the affected skin area), angioedema (swelling of the skin and mucosa).

Side effects with unknown frequency:
Blood disorders: pure red cell aplasia (a severe form of anaemia in which red blood cell production is reduced or stopped); may lead to symptoms such as profound fatigue and lack of energy
Immune system disorders: Vogt-Koyanagi-Harada disease – a rare condition characterised by loss of vision, hearing and skin pigmentation; rejection of liver and kidney transplants
Psychiatric and nervous system disorders: mania (episodes of abnormally elevated mood) and bipolar disorders (episodes of abnormally elevated mood alternating with sadness and despair); thoughts of threatening others' lives, stroke
Eye disorders: rare form of fluid accumulation under the retina causing retinal detachment
Cardiac and vascular disorders: peripheral ischaemia (inadequate blood supply to the extremities)
Gastrointestinal disorders: ischaemic colitis (inadequate blood supply to the intestine), change in tongue colour
Musculoskeletal disorders: severe muscle damage and pain.
Pulmonary arterial hypertension – a disease causing severe narrowing of the blood vessels in the lungs, leading to increased pressure in the vessels carrying blood from the heart to the lungs. This may occur particularly in patients with risk factors such as HIV infection or severe liver problems (cirrhosis). This side effect may develop at various times during treatment, usually several months after starting Pegasys therapy.

When Pegasys is used alone in patients with hepatitis B or C, some of these side effects occur less frequently.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pegasys

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C - 8 °C). Do not freeze. Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that the vial or its packaging is damaged, if the solution is cloudy or contains floating particles, or if the medicine shows any discoloration other than colourless to pale yellow.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pegasys contains

• The active substance is peginterferon alfa-2a. Each vial contains a 1.0 mL solution with 180 micrograms of peginterferon alfa-2a.
• The excipients are sodium chloride, polysorbate 80, benzyl alcohol, sodium acetate, acetic acid, and water for injections.

Description of the appearance of Pegasys and contents of the pack
Pegasys is a solution for injection supplied in a vial (1 mL), available in packs containing 1 or 4 single-dose vials. Not all pack sizes may be marketed.
Marketing Authorization Holder
pharmaand GmbH
Taborstrasse 1
1020 Wien
Austria
Manufacturer
Loba biotech GmbH
Fehrgasse 7
2401 Fischamend
Austria
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .
How to administer Pegasys
The following instructions explain how to self-inject or administer an injection to a child using the contents of a single-dose vial of Pegasys. Read the instructions carefully and follow them step by step. Your doctor or a healthcare professional will instruct you on how to administer the injections.
Preparation
Wash your hands thoroughly before use.
Gather all necessary materials before starting:
Included in the pack:

• one vial of Pegasys solution for injection. Not included in the pack:
• one 1 mL syringe
• one long needle for drawing Pegasys from the vial
• one short needle for subcutaneous injection
• cotton wool for cleaning
• a small dressing or sterile gauze
• an adhesive plaster
• a container for disposal of waste materials.

Measuring the dose of Pegasys

• Remove the protective cap from the Pegasys vial (1) .

• Clean the rubber stopper of the vial with cotton wool. You may keep the cotton wool to clean the skin area where you will inject Pegasys.
• Remove the syringe from its packaging. Do not touch the tip of the syringe.
• Take the long needle and firmly attach it to the tip of the syringe (2) .

• Remove the needle cover without touching the needle and hold the syringe with the attached needle.
• Insert the needle through the rubber stopper of the Pegasys vial (3) .

• Hold the vial and syringe together in one hand and invert the vial and syringe (4) .

With the syringe pointing upwards, ensure the tip of the needle is immersed in the Pegasys solution.
The other hand will be free to operate the plunger.

• Slowly pull back the plunger to draw into the syringe a volume slightly greater than the dose prescribed by your doctor.
• While keeping the syringe with the needle attached in the vial and pointing upwards, detach the syringe from the long needle, leaving the needle in the vial, without touching the tip of the syringe.
• Take the short needle and firmly attach it to the tip of the syringe (5) .

• Remove the needle cover.
• Check for air bubbles in the syringe. If you see any bubbles, gently pull back the plunger slightly. To remove air bubbles, hold the syringe with the needle pointing upwards. Gently tap the syringe to move the bubbles to the top. Slowly push the plunger down until the correct dose remains. Replace the needle cover and place the syringe horizontally until you are ready to use it.
• Allow the solution to reach room temperature before injection, or warm the syringe in your hands.
• Visually inspect the solution before administration: do not use if discolored or if particles are present. You are now ready to administer the injection.

Injecting the solution

• Select an injection site on the abdomen or thigh (avoiding the navel or waistline). Change the injection site each time.
• Clean and disinfect the skin with cotton wool at the injection site.
• Wait until the area is completely dry.
• Remove the needle cover.
• With one hand, pinch a fold of loose skin. With the other hand, hold the syringe like a pencil.
• Insert the needle fully into the raised skin at an angle between 45° and 90° (6) .

• Inject the solution by slowly and completely pushing the plunger down.
• Remove the needle from the skin.
• Press the injection site with a small dressing or sterile gauze, if needed, for a few seconds.

Do not massage the injection site. If bleeding occurs, cover with an adhesive plaster.
Disposal of used injection materials
The syringe, needle, and all materials used for the injection are for single use only and must be disposed of after the injection. Dispose of the syringe and needle safely in a closed container. Ask your doctor, hospital, or pharmacist for an appropriate disposal container.

Package leaflet: information for the user

Pegasys 90 micrograms injectable solution in pre-filled syringe, 135 micrograms injectable solution in pre-filled syringe, 180 micrograms injectable solution in pre-filled syringe

peginterferon alfa-2a
Please read 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Pegasys is and what it is used for

Pegasys contains the active substance peginterferon alfa-2a, a long-acting interferon.
Interferon is a protein that modifies the immune system's response (the body's defence system), helping it fight infections and serious diseases, and block the growth of cancer cells.
Pegasys is used for the treatment of polycythaemia vera or essential thrombocythaemia in adults.
Polycythaemia vera and essential thrombocythaemia are rare types of cancer in which the bone marrow produces too many red blood cells, white blood cells, and platelets (cells that help the blood to clot).
Polycythaemia vera and essential thrombocythaemia: Pegasys is used alone.
Pegasys is also used for the treatment of chronic hepatitis B or C in adults. It is also used for the treatment of chronic hepatitis B in children and adolescents aged 3 years and older, and chronic hepatitis C in children and adolescents aged 5 years and older who have not been previously treated. Both chronic hepatitis B and C are viral infections of the liver.
Chronic hepatitis B: Pegasys is usually used alone.
Chronic hepatitis C: Pegasys is used in combination with other medicines for the treatment of chronic hepatitis C (CHC).
Please also consult the package leaflets of any other medicines used in combination with Pegasys.

2. What you need to know before using Pegasys

Do not use Pegasys

• if you are allergic to peginterferon alfa-2a, to any interferon, or to any of the other ingredients of this medicine (listed in section 6);
• if you have ever had a heart attack or have been hospitalized due to severe chest pain in the last 6 months;
• if you have or have ever had an autoimmune disease (such as rheumatoid arthritis, psoriasis, or inflammatory bowel disease);
• if you have a thyroid disorder that is not controlled by medication;
• if you have advanced liver disease and your liver does not function properly (e.g., your skin has turned yellow);
• if the patient is a child under 3 years of age;
• if the patient is a child who has previously had severe psychiatric disorders, such as severe depression or suicidal thoughts;
• if you are infected with both hepatitis C virus and human immunodeficiency virus (HIV) and your liver does not function properly (e.g., your skin has turned yellow);
• if you are being treated with telbivudine, a medicine used to treat hepatitis B virus infection (see section "Other medicines and Pegasys").

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pegasys:

• if you have had a serious mental or neurological disorder;
• if you have ever had depression or symptoms associated with depression (e.g., feelings of sadness, hopelessness, etc.);
• if you are an adult who has or has had a history of substance abuse (alcohol or drugs);
• if you have psoriasis, as this condition may worsen during treatment with Pegasys;
• if you have a liver problem other than hepatitis B or C;
• if you have diabetes or high blood pressure, your doctor may require an eye examination;
• if you know you have VKH syndrome;
• if you have a thyroid disorder not well controlled by medication;
• if you have had anaemia;
• if you have undergone or are scheduled to undergo an organ transplant (liver or kidney) in the near future;
• if you also have an HIV (human immunodeficiency virus) infection and are being treated with anti-HIV drugs;
• if you previously discontinued hepatitis C therapy due to anaemia or low blood cell counts.

While starting treatment with Pegasys, inform your doctor, nurse, or pharmacist:

• if you develop symptoms associated with depression (e.g., feelings of sadness, hopelessness, etc.) (see section 4);
• if you notice any changes in vision;
• if you develop symptoms of cold or other respiratory infections (such as cough, fever, or difficulty breathing);
• if you suspect you have an infection (e.g., pneumonia), as you may temporarily have an increased risk of infections while taking Pegasys;
• if you develop signs of bleeding or unusual bruising, consult your doctor immediately;
• if you develop signs of a severe allergic reaction (such as difficulty breathing, wheezing, or hives) while taking the medicine, seek urgent medical attention;
• if you develop symptoms of Vogt-Koyanagi-Harada (VKH) syndrome; a group of disorders including neck stiffness, headache, loss of skin and hair pigmentation, vision disturbances (such as blurred vision), and/or hearing changes (such as ringing in the ears).

During treatment, your doctor will regularly perform blood tests to monitor changes in white blood cells (cells that fight infection), red blood cells (cells that carry oxygen), platelets (cells involved in blood clotting), liver function, blood glucose (blood sugar levels), or other laboratory values.

Dental and gum disorders, which may lead to tooth loss, have been reported in patients treated with Pegasys in combination with ribavirin. In addition, dry mouth may have a harmful effect on teeth and oral mucosa during prolonged treatment with Pegasys and ribavirin. You should brush your teeth thoroughly twice daily and attend regular dental check-ups. Furthermore, some patients may experience vomiting. In such cases, make sure to rinse your mouth thoroughly after vomiting.

Children and adolescents
Indication for polycythaemia vera and essential thrombocythaemia:
Pegasys must not be given to children or adolescents, as there is no information available on the use of Pegasys in this age group for these indications.

Indication for chronic hepatitis B and C:
Pegasys may only be used in children and adolescents with chronic hepatitis C aged 5 years and older, or in children and adolescents with chronic hepatitis B aged 3 years and older. Pegasys must not be given to children under 3 years of age because it contains benzyl alcohol, which may cause toxic or allergic reactions in these children.

• If the child has or has had a psychiatric disorder, discuss this with the doctor, who will monitor the child for signs or symptoms of depression (see section 4).
• During treatment with Pegasys, the child may experience slowed growth and development (see section 4).

Other medicines and Pegasys
Do not use Pegasys if you are taking telbivudine (see section "Do not use Pegasys"), as the combination of these medicines increases the risk of developing peripheral neuropathy (numbness, tingling, and/or burning sensations in the arms and/or legs). Therefore, the combination of Pegasys with telbivudine is contraindicated. Inform your doctor or pharmacist if you are being treated with telbivudine.

Inform your doctor if you are taking medicines for asthma, as your asthma medication dose may need to be adjusted.

If you are also infected with HIV: inform your doctor if you are receiving anti-HIV therapy. Lactic acidosis and worsening of liver function are adverse effects associated with highly active antiretroviral therapy (HAART), a treatment for HIV. If you are receiving HAART, adding Pegasys plus ribavirin may increase the risk of lactic acidosis or liver failure. Your doctor will monitor you for signs and symptoms of these conditions. Patients treated with zidovudine in combination with ribavirin and alpha interferons have an increased risk of developing anaemia. Patients treated with azathioprine in combination with ribavirin and peginterferon have an increased risk of developing severe blood disorders. Be sure to also read the ribavirin package leaflet.

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

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

When Pegasys is used in combination with ribavirin, both male and female patients must take special precautions during sexual activity if there is any chance of pregnancy, because ribavirin can be very harmful to the unborn child:

• if you are a woman of childbearing potential taking Pegasys in combination with ribavirin, you must have a negative pregnancy test before starting treatment, every month during treatment, and for 4 months after completing treatment. You must use an effective contraceptive method during treatment and for 4 months after completing treatment. This can be discussed with your doctor;
• if you are a man taking Pegasys in combination with ribavirin, avoid sexual intercourse with pregnant women unless you use a condom. This reduces the likelihood of ribavirin being transferred to the woman's body. If your female partner is not pregnant but is of childbearing potential, she must have a pregnancy test every month during treatment and for 7 months after completing treatment. You and your partner must use an effective contraceptive method during treatment and for 7 months after completing treatment. This can be discussed with your doctor.

Ask your doctor or pharmacist for advice before taking any medicine. It is not known whether this product passes into breast milk. Therefore, do not breastfeed while taking Pegasys. Regarding combination therapy with ribavirin, refer to the information contained in the package leaflets of medicines containing ribavirin.

Also consult the package leaflets of any other medicines used in combination with Pegasys.

Driving and using machines
If you feel drowsy, tired, or confused while taking Pegasys, do not drive or operate machinery.

Pegasys contains benzyl alcohol, polysorbate 80, and sodium
This medicine contains 5 mg of benzyl alcohol per pre-filled syringe, equivalent to 10 mg/mL.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with the risk of serious adverse effects, including breathing problems (gasping syndrome), in young children.
Pegasys must not be given to premature infants, newborns, or children under 3 years of age.
Consult your doctor or pharmacist if you are pregnant or breastfeeding, or if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).
This medicine contains 0.025 mg of polysorbate 80 per pre-filled syringe, equivalent to 0.05 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have known allergies.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to use Pegasys

Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist.

Dosage of Pegasys

Your doctor will determine the exact dose of Pegasys and tell you how often to take it. If necessary, the dose may be adjusted during treatment. Do not exceed the recommended dose.

Polycythaemia vera and essential thrombocythaemia – in adults

For the treatment of polycythaemia vera and essential thrombocythaemia, Pegasys is administered alone at an initial recommended dose of 45 micrograms once weekly by subcutaneous injection. This dose is usually gradually increased by monthly increments of 45 micrograms up to a maximum of 180 micrograms once weekly by subcutaneous injection.

Your doctor may adjust the dose and/or increase the dosing interval.

Hepatitis B and C – in adults

Pegasys is used alone only if, for any reason, you cannot take ribavirin.

Pegasys, used alone or in combination with ribavirin, is generally administered at a dose of 180 micrograms once weekly. See also the following sections regarding combination therapies.

The duration of combination therapy varies from 4 to 18 months depending on the characteristics of the virus infecting you, your response to treatment, and whether you have been previously treated.

Discuss this with your doctor and follow the recommended treatment duration.

Pegasys injection should normally be given at bedtime.

Use in children and adolescents

Hepatitis B (from age 3 years) and hepatitis C (from age 5 years)

Your doctor will determine the exact dose of Pegasys for the child and tell you how often to administer it. The usual dose of Pegasys, when given in combination with ribavirin, is based on the child's height and weight. If necessary, the dose may be adjusted during treatment. Use of Pegasys pre-filled syringes is recommended for children and adolescents, as they allow dose adjustment. Do not exceed the recommended doses.

The duration of combination therapy in children with chronic hepatitis C varies from 6 to 12 months and depends on the type of virus that caused the child’s infection and the response to therapy.

In chronic hepatitis B, the duration of treatment with Pegasys is 48 weeks. Confirm with your doctor and follow the recommended treatment duration. Pegasys injection is usually given before going to bed.

Pegasys is intended for subcutaneous use (under the skin). Therefore, Pegasys is injected with a short needle into the subcutaneous fatty tissue of the abdomen or thigh. If you are administering the injection yourself, you will be instructed on how to self-inject. Detailed instructions are provided at the end of this leaflet (see section “How to administer Pegasys”).

Use Pegasys exactly as instructed by your doctor, for the duration prescribed.

If you feel that the effect of Pegasys is too strong or too weak, consult your doctor or pharmacist.

Combination therapy with ribavirin in chronic hepatitis C (all patients aged 5 years and older)

When undergoing combination therapy with Pegasys and ribavirin, follow the dosing regimen recommended by your doctor.

Combination therapy with other medicines in chronic hepatitis C (all patients aged 5 years and older)

When undergoing combination therapy with Pegasys, follow the dosing regimen recommended by your doctor and also consult the package leaflets of any other medicines used in combination with Pegasys.

If you use more Pegasys than you should

Contact your doctor or pharmacist as soon as possible.

If you forget to take Pegasys

If you realize you have missed the injection 1 or 2 days after the scheduled time, inject the recommended dose as soon as possible. Take the next dose according to the regular schedule.

If you realize you have missed the injection 3 to 5 days after the scheduled time, take the recommended dose as soon as possible. Then take subsequent doses at 5-day intervals until you return to your originally scheduled day of the week.

For example: You normally inject Pegasys on Monday. On Friday, you remember you missed Monday’s injection (4 days late). You should inject the missed dose immediately (on Friday) and administer the next dose on Wednesday (5 days after Friday). The following dose will be on Monday, 5 days after Wednesday. You are now back on your regular schedule and should continue weekly injections every Monday.

If you realize you have missed the injection 6 days after the scheduled time, wait and inject the dose on the next scheduled day.

Contact your doctor or pharmacist if you need help managing a missed dose of Pegasys.

Do not take a double dose to make up for a forgotten dose.

If you have any questions about the use of Pegasys, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Pegasys can cause side effects, although not everyone gets them.
Some patients become depressed during treatment with Pegasys alone or in combination with ribavirin, and in some cases suicidal thoughts or aggressive behaviour (sometimes directed towards other people, such as thoughts of threatening others' lives) may occur. Some patients have died by suicide. Seek urgent medical help if you notice the onset of depression, suicidal thoughts, or changes in your behaviour. Ask a family member or friend to help you promptly identify any signs of depression or changes in your behaviour.

Growth and development (children and adolescents):
Some children and adolescents treated with Pegasys for chronic hepatitis B for 48 weeks did not grow or gain weight as expected for their age. It is not yet known whether they will eventually reach the expected adult height and weight after completing therapy.
With up to one year of treatment with Pegasys in combination with ribavirin, some children and adolescents with chronic hepatitis C do not grow or gain weight as expected. Although many children catch up to their expected height within two years after completing treatment, and most of the remaining children within six years after treatment completion, treatment with Pegasys may still affect final adult height.

Contact your doctor immediately if you notice any of the following side effects: severe chest pain; persistent cough; irregular heartbeat; difficulty breathing; confusion; depression; severe stomach ache; blood in the stool (or black, tarry stools); severe nosebleeds; fever or chills; vision problems. These side effects can be serious and you may need urgent medical attention.

Very common side effects with the combination of Pegasys and ribavirin (may affect more than 1 in 10 people) are:
Metabolic disorders: loss of appetite
Psychiatric disorders and nervous system disorders: depression (feeling down, uncomfortable with oneself, or hopeless), anxiety, difficulty sleeping, headache, difficulty concentrating, dizziness
Respiratory disorders: cough, shortness of breath
Gastrointestinal disorders: diarrhoea, nausea, abdominal pain
Skin disorders: hair loss, skin reactions (including itching, dermatitis, dry skin)
Musculoskeletal disorders: joint and muscle pain
Systemic disorders: fever, weakness, fatigue, tremors and chills, pain, irritation at the injection site, irritability (mood swings).

Common side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 10 people) are:
Infections: fungal, viral, and bacterial infections. Upper respiratory tract infections, bronchitis, oral fungal infections (mycosis), and herpes (a common recurring viral infection affecting the lips and mouth)
Blood disorders: reduced platelet count (affecting blood clotting), anaemia (reduced red blood cell count), swollen lymph glands
Endocrine disorders: increased or decreased thyroid function
Psychiatric and nervous system disorders: mood changes, aggression, irritability, reduced sex drive, poor memory, fainting, muscle weakness, migraine, numbness, tingling, burning sensations, tremor, taste disturbances, nightmares, drowsiness
Eye disorders: blurred vision, eye pain, eye inflammation, dry eyes
Ear disorders: ear pain
Cardiac and vascular disorders: rapid heartbeat, palpitations, swelling of extremities, hot flushes
Respiratory disorders: shortness of breath during activity, nosebleeds, inflammation of the nose and throat, nasal and paranasal sinus infections (air-filled spaces in the bones of the head and face), runny nose, sore throat
Gastrointestinal disorders: vomiting, indigestion, difficulty swallowing, mouth ulcers, bleeding gums, inflammation of the tongue and mouth, flatulence (excessive air or gas), dry mouth, weight loss
Skin disorders: skin rash, increased sweating, psoriasis, hives, eczema, photosensitivity (sensitivity to sunlight), night sweats
Musculoskeletal disorders: back pain, joint inflammation, muscle weakness, bone pain, neck pain, muscle pain, muscle cramps
Reproductive system disorders: impotence (inability to maintain an erection)
Systemic disorders: chest pain, influenza-like illness, malaise (feeling unwell), lethargy, hot flushes, thirst.

Uncommon side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 100 people) are:
Infections: lung infection, skin infections
Benign and malignant tumours: liver tumour
Immune system disorders: sarcoidosis (areas of inflamed tissue developing throughout the body), thyroid inflammation
Endocrine disorders: diabetes (high blood sugar levels)
Metabolic disorders: dehydration
Psychiatric and nervous system disorders: suicidal thoughts, hallucinations, peripheral neuropathy (nerve disorder affecting the extremities)
Eye disorders: retinal haemorrhage (bleeding at the back of the eye)
Ear disorders: hearing loss
Cardiac and vascular disorders: high blood pressure
Respiratory disorders: wheezing
Gastrointestinal disorders: gastrointestinal bleeding
Liver disorders: impaired liver function.

Rare side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 1,000 people) are:
Infections: heart infection, outer ear infection
Blood disorders: severe reduction in red blood cells, white blood cells, and platelets
Immune system disorders: severe allergic reactions, systemic lupus erythematosus (a disease in which the body attacks its own cells), rheumatoid arthritis (an autoimmune disease)
Endocrine disorders: diabetic ketoacidosis, a complication of uncontrolled diabetes
Psychiatric and nervous system disorders: suicide, psychotic disorders (severe personality disturbances and deterioration of normal social functioning), coma (prolonged deep unconsciousness), seizures, facial paralysis (weakness of facial muscles)
Eye disorders: inflammation and swelling of the optic nerve, retinal inflammation, corneal ulceration
Cardiac disorders: heart attack, heart failure, chest pain, rapid heartbeat, heart rhythm abnormalities, or inflammation of the lining of the heart and heart muscle
Vascular disorders: cerebral haemorrhage and blood vessel inflammation
Respiratory disorders: interstitial pneumonia (lung inflammation, including fatal outcomes), blood clots in the lungs
Gastrointestinal disorders: stomach ulcer, pancreatitis (inflammation of the pancreas)
Liver disorders: liver failure, bile duct inflammation, fatty liver
Musculoskeletal disorders: muscle inflammation
Renal disorders: kidney failure
Injury or poisoning: overdose of substances.

Very rare side effects with the combination of Pegasys and ribavirin (may affect up to 1 in 10,000 people) are:
Blood disorders: aplastic anaemia (failure of bone marrow to produce red blood cells, white blood cells, and platelets)
Immune system disorders: idiopathic or thrombotic thrombocytopenic purpura (increased bruising, bleeding, reduced platelet count, anaemia, and extreme weakness)
Eye disorders: loss of vision
Skin disorders: toxic epidermal necrolysis/Stevens-Johnson syndrome/multiform erythema (a range of skin rashes with varying severity, including death, which may be associated with blisters in the mouth, nose, eyes, and other mucous membranes, and skin detachment), angioedema (swelling of the skin and mucosa).

Side effects with unknown frequency:
Blood disorders: pure red cell aplasia (a severe form of anaemia in which red blood cell production is reduced or stopped); may lead to symptoms such as profound fatigue and lack of energy
Immune system disorders: Vogt-Koyanagi-Harada disease – a rare condition characterised by loss of vision, hearing, and skin pigmentation; rejection of liver and kidney transplants
Psychiatric and nervous system disorders: mania (episodes of abnormally elevated mood), bipolar disorders (episodes of abnormally elevated mood alternating with sadness and despair); thoughts of threatening others' lives, stroke
Eye disorders: rare form of retinal detachment with fluid in the retina
Cardiac and vascular disorders: peripheral ischaemia (inadequate blood supply to the extremities)
Gastrointestinal disorders: ischaemic colitis (inadequate blood supply to the intestine), change in tongue colour
Musculoskeletal disorders: severe muscle damage and pain.

Pulmonary arterial hypertension – a disease causing severe narrowing of the blood vessels in the lungs, leading to increased pressure in the vessels carrying blood from the heart to the lungs. This may occur particularly in patients with risk factors such as HIV infection or severe liver problems (cirrhosis). This side effect may develop at various times during treatment, usually several months after starting Pegasys therapy.

When Pegasys is used alone in patients with hepatitis B or C, some of these side effects occur less frequently.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pegasys

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that the packaging of the syringe or needle is damaged, if the solution is cloudy or contains floating particles, or if the medicine has changed colour and is not colourless to pale yellow.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Pegasys contains

• The active substance is peginterferon alfa-2a. Each pre-filled syringe contains 0.5 mL of solution and 90.135 or 180 micrograms of peginterferon alfa-2a.
• The excipients are sodium chloride, polysorbate 80, benzyl alcohol, sodium acetate, acetic acid and water for injections.

Description of the appearance of Pegasys and package contents
Pegasys is a solution for injection supplied in a pre-filled syringe (0.5 mL) with a separate injection needle.
Pegasys 90 micrograms solution for injection in pre-filled syringe
The syringe is marked with graduations corresponding to 90 micrograms (mcg), 65 mcg, 45 mcg, 30 mcg, 20 mcg and 10 mcg. It is available in packs containing 1 pre-filled syringe.
Pegasys 135 micrograms solution for injection in pre-filled syringe
The syringe is marked with graduations corresponding to 135 micrograms (mcg), 90 mcg and 45 mcg. It is available in packs containing 1, 4 or a multiple pack of 12 (2 packs of 6) pre-filled syringes.
Not all pack sizes may be marketed.
Pegasys 180 micrograms solution for injection in pre-filled syringe
The syringe is marked with graduations corresponding to 180 micrograms (mcg), 135 mcg and 90 mcg. It is available in packs containing 1, 4 or a multiple pack of 12 (2 packs of 6) pre-filled syringes.
Not all pack sizes may be marketed.
Marketing Authorization Holder
pharmaand GmbH
Taborstrasse 1
1020 Wien
Austria
Manufacturer
Loba biotech GmbH
Fehrgasse 7
2401 Fischamend
Austria
More detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu .
How to administer Pegasys
The following instructions explain how to self-inject or administer the contents of a Pegasys pre-filled syringe to a child. Read the instructions carefully and follow them step by step. Your doctor or a member of their staff will instruct you on how to administer the injections.
Preparation
Wash your hands thoroughly before use.
Gather all necessary materials before starting:
Included in the package:

• one pre-filled syringe of Pegasys
• one injection needle. Not included in the package:
• cotton for cleaning
• a small dressing or sterile gauze
• an adhesive plaster
• a container for disposal of waste materials.

Preparing the syringe and injection needle

• Remove the protective cap covering the back of the needle (1-2) .

• Remove the rubber cap from the syringe (3) . Do not touch the tip of the syringe.

• Firmly attach the needle to the tip of the syringe (4) .

• Remove the needle cap (5) .

• To remove air bubbles from the syringe, hold the syringe with the needle pointing upwards. Gently tap the syringe to bring any air bubbles to the top. Slowly push the plunger to the correct dose, until the end of the plunger reaches the syringe mark corresponding to the required dose. Replace the needle cap and place the syringe horizontally until ready for use.
• Allow the solution to reach room temperature before injection or warm the syringe between your hands.
• Visually inspect the solution before administration: do not use if discolored or if particles are present.

You are now ready to administer the injection.
Injecting the solution

• Choose an injection site on the abdomen or thigh (avoiding the navel or waistline). Change the injection site each time.
• Clean and disinfect the skin with cotton at the injection site.
• Wait until the area is completely dry.
• Remove the needle cap.
• With one hand, pinch a fold of skin. With the other hand, hold the syringe like a pencil.
• Insert the needle fully into the raised skin at an angle between 45° and 90° (6) .

• Inject the solution by slowly and completely pushing the plunger down from the graduation mark corresponding to the appropriate dose.
• Remove the needle from the skin.
• Press the injection site with a small dressing or sterile gauze, if needed, for a few seconds.

Do not massage the injection site. If bleeding occurs, cover with an adhesive plaster.
Disposal of used injection materials
The syringe, needle and all materials used for the injection are for single use only and must be disposed of after the injection. Dispose of the syringe and needle safely in a closed container. Ask your doctor, hospital or pharmacist for an appropriate disposal container.