Pegasys 135 micrograms solution for injection in pre-filledsyringe

Pegasys is a long-acting interferon. Interferon is a protein that modifies the response of the body's immune system to help fight infections and severe diseases. Pegasys is used for the treatment of chronic hepatitis B or C, which are viral infections of the liver.

Chronic Hepatitis B: Pegasys is usually used alone.
Chronic Hepatitis C: Pegasys is best used for this treatment in combination with ribavirin. If you receive combination therapy of Pegasys and ribavirin, you should also read the ribavirin package leaflet.
Pegasys is used alone only if you cannot take ribavirin for any reason.

Do not use Pegasys:

• if you are allergic to peginterferon-alfa-2a, to any interferon or any of the other ingredients of Pegasys.
• if you have ever had a heart attack or suffer from other heart disease.
• if you have, so called autoimmune hepatitis.
• if you have advanced liver disease (e.g. your skin has become yellow).
• if the patient is a child less than 3 years old.
• if you are being treated with telbivudine (see ?Taking other medicines?).

Take special care with Pegasys:

Tell your doctor:

• if you are planning on becoming pregnant, discuss this with your doctor before starting to use Pegasys (see Pregnancy).
• if you have psoriasis, it may get worse during treatment with Pegasys.
• if you have a problem with your liver other than hepatitis B or C.
• if you have diabetes or high blood pressure, your doctor may ask you to have an eye examination.
• if you notice a change in your vision.
• when receiving Pegasys, you may temporarily have a greater risk of getting an infection. Check with your doctor if you think you are getting an infection (such as pneumonia).
• if you develop symptoms associated with a cold or other respiratory infection (such as cough, fever or any difficulty in breathing).
• if you develop any signs of bleeding or unusual bruising, check with your doctor immediately.
• if you develop signs of a severe allergic reaction (such as difficulty in breathing, wheezing or hives) while on this medication, seek medical help immediately.
• if you have thyroid disease that is not well controlled with medicines.
• if you have had a severe nervous or mental disorder.
• if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, dejection etc) while on treatment with Pegasys (see section 4).
• if you have ever had anaemia.
• if you are coinfected with HIV and treated with anti HIV medicinal products.
• if you have been withdrawn from previous therapy for Hepatitis C because of anaemia or low blood count.

Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Pegasys and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and membranes of the mouth during long-term treatment with the combination of Pegasys with ribavirin. You should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly afterwards.

Taking other medicines:
Tell your doctor if you are taking medicines for asthma, because the dose for your asthma medicine may need to be changed.
Patients who also have HIV infection. Tell your doctor if you are taking anti-HIV therapy. Lactic acidosis and worsening liver function are side effects associated with Highly Active Anti-Retroviral Therapy (HAART) an HIV treatment. If you are receiving HAART, the addition of Pegasys + ribavirin may increase your risk of lactic acidosis or liver failure. Your doctor will monitor you for signs and symptoms of these conditions. Patients receiving zidovudine in combination with ribavirin and alpha interferons are at increased risk of developing anaemia. Patients receiving azathioprin in combination with ribavirin and peginterferon are at increased risk of developing severe blood disorders. Please be sure to read the ribavirin Patient Leaflet also.
Do not use Pegasys if you are taking telbivudine (see ?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. Tell your doctor or pharmacist if you are being treated with telbivudine.

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed.

Pregnancy:
Ask your doctor or pharmacist for advice before taking any medicine.
In studies in pregnant animal, interferons have sometimes caused miscarriage. The effect on human pregnancy is not known.
When Pegasys is used in combination with ribavirin, both male and female patients must take special precautions in their sexual activity if there is any chance for pregnancy to occur as ribavirin can be very damaging to an unborn baby:

• if you are a woman of childbearing age who is taking Pegasys in combination with ribavirin, youmust have a negative pregnancy test before treatment, each month during therapy and for the 4 months after treatment is stopped. You and your partner must each use an effective contraceptive during the time you are taking the treatment and for 4 months after stopping treatment. This can be discussed with your doctor.
• if you are a man who is taking Pegasys in combination with ribavirin, do not have sex with apregnant woman unless you use a condom. This will lessen the chance for ribavirin to be left in the woman?s body. If your female partner is not pregnant now but is of childbearing age, she must be

tested for pregnancy each month during treatment and for the 7 months after treatment has stopped. You and your partner must each use an effective contraceptive during the time you are taking the treatment and for 7 months after stopping treatment. This can be discussed with your doctor.

Breast-feeding:
Ask your doctor or pharmacist for advice before taking any medicine. It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you are taking Pegasys. In combination therapy with ribavirin, take notice of the respective informing texts of ribavirin containing medicinal products.

Driving and using machines:
Do not drive or use machinery if you feel drowsy, tired, or confused while taking Pegasys.

Important information about some of the ingredients of Pegasys:

Must not be given to premature babies or neonates. May cause toxic reactions and allergic reactions in infants and children up to 3 years old.

Always take Pegasys as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. Your doctor has prescribed Pegasys specifically for you and your current condition; do not share this medicine with anyone else.

Pegasys dosing
Your doctor has determined the exact dose of Pegasys, and will tell you how often to use it. If necessary, the dose may be changed during treatment. Do not exceed the recommended dose.

Pegasys given alone or in combination with ribavirin is usually given at a dose of 180 micrograms once a week.
The duration of combination treatment varies from 4 to 18 months depending on the type of virus you are infected with, on treatment response and whether you have been treated before. Please check with your doctor and follow the recommended duration of treatment. Pegasys injection is normally taken at bedtime.

Pegasys is intended for subcutaneous use (under the skin). This means that Pegasys is injected with a short needle into the fatty tissue under the skin in the abdomen or thigh. If you are injecting this medicine yourself, you will be instructed how to give the injection. Detailed instructions are provided at the end of this leaflet (see ?How to self-inject Pegasys?).

Use Pegasys exactly as described by your doctor, for as long as prescribed by your doctor If you have the impression that the effect of Pegasys is too strong or too weak, talk to your doctor or pharmacist.

Combination therapy with ribavirin in chronic hepatitis C
In the case of combination therapy with Pegasys and ribavirin, please follow the dosing regimen recommended by your doctor.

-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 realise you missed your injection 1 or 2 days after it was scheduled, you should inject your recommended dose as soon as possible. Take your next injection on the regularly scheduled day. If you realise you missed your injection 3 to 5 days after it was scheduled, you should take your injection at the recommended dose as soon as possible. Take your next doses at 5 day intervals until you return to your regularly scheduled day of the week.

As an example: Your regular weekly Pegasys injection is on Monday. You remember on Friday that you forgot to take your injection on Monday (4 days late).You should inject your regularly scheduled dose immediately on Friday and take your next injection on Wednesday (5 days after your Friday dose). Your next injection will be on the Monday, 5 days later after the Wednesday injection. You are now back on your regularly scheduled day and should continue your injections every Monday.
If you realise you missed your injection 6 days after it was scheduled, you should wait and take your dose on the next day, your regularly scheduled day.
Contact your doctor or pharmacist if you need any help determining how to manage a missed dose of Pegasys.

Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist

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

Some people get depressed when taking Pegasys alone or in combination treatment with ribavirin, and in some cases people have had suicidal thoughts or aggressive behaviour (sometimes directed against others such as thoughts about threatening the life of the others). Some patients have actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend to help you stay alert to signs of depression or changes in your behaviour.

During treatment your doctor will take blood samples regularly to check for changes in your white blood cells (cells that fight infection), red blood cells (cells that carry oxygen), platelets (blood clotting cells), liver function or changes in other laboratory values.

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

Very common side effects with the combination of Pegasys and ribavirin (occurring in more than 10 out of 100 patients) are:

Metabolic disorders: Loss of appetite
Psychiatric disorders: feeling depressed (feeling low, feeling bad about yourself or feeling hopeless), anxiety, inability to sleep
Nervous system disorders: Headache, difficulty concentrating and dizziness
Respiratory disorders: cough, shortness of breath
Gastrointestinal disorders: diarrhoea, nausea, abdominal pain
Skin disorders: loss of hair, and skin reactions (including itching, dermatitis and dry skin). Musculoskeletal disorders: pain in joints and muscles
General disorders: fever, weakness, tiredness, shaking, chills, pain, injection site irritation and irritability (getting easily upset)

Common side effects with the combination of Pegasys and ribavirin occurring in more than 1 out of 100 patients:

Infections: Fungal, viral and bacterial infections. Upper respiratory infection, bronchitis, fungal infection of the mouth and herpes (a common recurring viral infection affecting the lips, mouth) Blood disorders: Low platelet count (affecting the clotting ability), anaemia (low red cell count) and enlarged lymph glands.
Endocrine disorders: overactive and underactive thyroid gland

Psychiatric disorders: Mood /emotion changes, aggression, nervousness, decreased sexual desire Nervous system disorders: Poor memory, fainting, decreased muscle strength, migraine, numbness, tingling, burning sensation, tremor, changes in the sense of taste, nightmares, sleepiness Eye Disorders: Blurry vision, eye pain, eye inflammation and dry eyes.
Ear disorders: Sensation of room spinning, ear pain
Cardiac disorders: Rapid heart rate, pulsation of the heart beats, swelling in the extremities. Vascular disorders: Flushing
Respiratory disorders: shortness of breath with activity, nose bleeds, nose and throat inflammation, infections of the nose and sinuses (air-filled spaces found in the bones of the head and face), runny nose, sore throat.

Gastrointestinal disorders: Vomiting, indigestion, difficulty swallowing, mouth ulceration, bleeding gums, inflammation of tongue and mouth, flatulence (excess amount of air or gases), dry mouth and loss of weight.
Skin disorders: Rash, increased sweating, psoriasis, hives, eczema, 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)
General disorders: Chest pain, flu-like illness, malaise (not feeling well), lethargy, hot flushes, thirst

Uncommon side effects with the combination of Pegasys and ribavirin occurring in more than 1 out of 1000 patients:

Infections: Lung infection, skin infections
Neoplasms benign and malignant disorders: Liver tumour
Immune disorders: sarcoidosis (areas of inflamed tissue occurring throughout the body), inflammation of the thyroid
Endocrine disorders: Diabetes (high blood sugar)
Metabolic disorders: Dehydration
Psychiatric disorders: Thoughts of suicide, hallucinations (severe problems with personality and deterioration in normal social functioning)
Nervous system disorders: Peripheral neuropathy (disorder of the nerves affecting the extremities) Eye disorders: Bleeding in the retina (back of the eye)
Ear disorders: Hearing loss
Vascular disorder: High blood pressure
Respiratory disorders: Wheezing
Gastrointestinal disorders: gastrointestinal bleeding
Liver disorders: Poor functioning of the liver

Rare side effects with the combination of Pegasys and ribavirin occurring in more than 1 in 10,000 patients:

Infections: Infection of the heart, infection of the external ear
Blood disorders: severe reduction in red blood cells, white blood cells and platelet
Immune system disorders: Severe allergic reaction, systemic lupus erythematosus (an illness where the body attacks its own cells), rheumatoid arthritis (an autoimmune disease)
Endocrine disorders: Diabetic ketoacidosis, a compilation of uncontrolled diabetes Psychiatric disorders: Suicide, psychotic disorders (severe problems with personality and deterioration in normal social functioning)
Nervous system disorders: Coma (a deep prolonged unconsciousness), seizures, facial palsy (weakness of the facial muscle)
Eye disorders: Inflammation and swelling of the optic nerve, inflammation of the retina, ulceration of the cornea
Cardiac disorders: Heart attack, heart failure, heart pain, rapid heart rhythm, rhythm disorders or inflammation of the lining of the heart and cardiac muscle.
Vascular disorders: Bleeding in the brain and inflammation in the vessels.

Respiratory disorders: Interstitial pneumonia (inflammation of the lungs including fatal outcome), blood clots in the lung
Gastrointestinal disorders: stomach ulcer, inflammation of the pancreas
Liver disorders: Liver failure, bile duct inflammation, fatty liver
Musculoskeletal disorders: Inflammation of the muscles
Renal disorders: renal failure
Injury or poisoning: Substance overdose

Very rare side effects with the combination of Pegasys and ribavirin occurring in less than 1 in 10,000 patients:

Blood disorders: aplastic anaemia (failure of the bone marrow to produce red blood cells, white blood cells and platelets). Pure red cell aplasia (a severe form of anemia where red blood cell production is decreased or stopped) has been very rarely reported; it can result in symptoms such as feeling very tired with no energy.
Immune System disorders: Idiopathic (or thrombotic) thrombocytopenic purpura (increased bruising, bleeding, decreased platelets, anaemia and extreme weakness)
Eye disorders: Loss of vision
Skin disorders: Toxic epidermal necrolysis/Stevens Johnson Syndrome/ erythema multiforme (a spectrum of rashes with varying degrees of severity including death which may be associated with blisters in the mouth, nose, eyes and other mucosal membranes and sloughing of the affected area of the skin), angioedema (swelling in the skin and mucosa).

Adverse events with unknown frequency:

Nervous system: Stroke
Eye disorders: Rare form of retinal detachment with fluid in the retina.
Gastrointestinal disorders: Ischaemic colitis (insufficient blood supply to the bowels). Musculoskeletal disorders: Serious muscle damage and pain.

When Pegasys is used alone in hepatitis B or C patients, some of these effects are less likely to occur. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Pegasys after the expiry date which is 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 carton in order to protect from light.

Do not use Pegasys if the syringe or needle packaging is damaged, if the solution is cloudy or if it has floating particles or if the medicine is any colour besides colourless to light yellow.

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

What Pegasys contains

• The active substance is peginterferon alfa-2a (conjugation of recombinant interferon alfa-2a with bis-[monomethoxy polyethylene glycol] of a molecular mass, Mn, of 40 000), 135 micrograms in a pre-filled syringe.
• The other ingredients are sodium chloride, polysorbate 80, benzyl alcohol, sodium acetate, acetic acid and water for injections.

What Pegasys looks like and contents of the pack

Pegasys is presented as a solution for injection in a pre-filled syringe (0.5 ml) with a separate injection needle available in packs containing 1, 4 or 12 pre-filled syringes.

Marketing Authorisation Holder and Manufacturer

Roche Registration Limited
6 Falcon Way
Shire Park
Welwyn Garden City
AL7 1TW
United Kingdom

Roche Pharma AG
Emil-Barell-Str.1
D-79639 Grenzach-Wyhlen
Germany

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

LuxembourgLuxemburg Voirsiehe BelgiqueBelgien BelgiëBelgiqueBelgien N.V. Roche S.A. TélTel 32 0 2 525 82 11

359 2 818 44 44 Magyarország Roche Magyarország Kft. Tel 36 - 23 446 800

Malta See United Kingdom eská republika Roche s. r. o. Tel 420 - 2 20382111

Danmark Roche as Tlf 45 - 36 39 99 99 Nederland Roche Nederland B.V. Tel 31 0 348 438050

Deutschland Roche Pharma AG Tel 49 0 7624 140 Norge Roche Norge AS Tlf 47 - 22 78 90 00

Eesti Roche Eesti OÜ Tel 372 - 6 177 380 Österreich Roche Austria GmbH Tel 43 0 1 27739

Roche Hellas A.E. 30 210 61 66 100 Polska Roche Polska Sp.z o.o. Tel 48 - 22 345 18 88

España Roche Farma S.A. Tel 34 - 91 324 81 00 Portugal Roche Farmacêutica Química, Lda Tel 351 - 21 425 70 00

France Roche Tél 33 0 1 46 40 50 00 România Roche România S.R.L. Tel 40 21 206 47 01

Ireland Roche Products Ireland Ltd. Tel 353 0 1 469 0700 Slovenija Roche farmacevtska druba d.o.o. Tel 386 - 1 360 26 00

Slovenská republika Roche Slovensko, s.r.o. Tel 421 - 2 52638201 Ísland Roche as co Icepharma hf Simi 354 540 8000

Italia Roche S.p.A. Tel 39 - 039 2471 SuomiFinland Roche Oy PuhTel 358 0 10 554 500

K .. . 357 - 22 76 62 76 Sverige Roche AB Tel 46 0 8 726 1200

Latvija Roche Latvija SIA Tel 371 - 6 7 039831 United Kingdom Roche Products Ltd. Tel 44 0 1707 366000

Lietuva

UAB ?Roche Lietuva?
Tel: +370 5 2546799

This leaflet was last approved in

HOW TO SELF- INJECT PEGASYS

The following instructions explain how to use Pegasys pre-filled syringes to inject yourself. Please read the instructions carefully and follow them step by step. Your doctor or his/her assistant will instruct you on how to give the injections.

Getting ready

Wash your hands carefully before handling any of the items.

Collect the necessary items before beginning:
Included in the pack:

• a pre-filled syringe of Pegasys
• an injection needle

Not included in the pack:

• a cleansing swab
• small bandage or sterile gauze
• an adhesive bandage
• a container for the waste material

Preparing the syringe and needle for injection

Remove the protective cap that covers the back of the needle 1-2.

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

Place the needle firmly on the tip of the syringe 4.

Remove the needle guard from the syringe needle 5.

To remove air bubbles from the syringe, hold the syringe with the needle pointing up. Tap the syringe gently to bring the bubbles to the top. Push the plunger up slowly to the correct dose. Replace the needle guard and place the syringe in a horizontal position until ready for use. Allow the solution to reach room temperature before injection or warm the syringe between your palms. Visually inspect the solution prior to administration do not use if it is discoloured or if particles are present.

You are now ready to inject the dose.

Injecting the solution

Select the injection site in the abdomen or thigh except your navel or waistline. Change your injection site each time. Clean and disinfect the skin where the injection is to be made with a cleansing swab. Wait for the area to dry. Remove the needle guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a pencil. Insert the needle all the way into the pinched skin at an angle of 45 to 90 6.

Inject the solution by gently pushing the plunger all the way down. Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if necessary for several seconds.

Do not massage the injection site. If there is bleeding, cover with an adhesive bandage.

Disposal of the injection materials

The syringe, needle and all injection materials are intended for single use and must be discarded after the injection. Dispose of the syringe and needle safely in a closed container. Ask your doctor, hospital or pharmacist for an appropriate container.