Herceptin 150 mg powder for concentrate for solution forinfusion

Herceptin contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates their growth. When Herceptin binds to HER2 it stops the growth of such cells and causes them to die.

Your doctor may prescribe Herceptin for the treatment of breast and gastric cancer when:

• You have early breast cancer, with high levels of a protein called HER2..
• You have metastatic breast cancer (i.e. breast cancer that has spread beyond the original tumour) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapy agents paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful. It is also used in combination with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (i.e. cancer that is sensitive to the presence of female sex hormones)
• You have metastatic gastric cancer with high levels of HER2, when it is in combination with the other cancer medicines capecitabine or 5-flououracil and cisplatin.

Do not use Herceptin

• If you are allergic to trastuzumab, to murine (mouse) proteins, or to any of the other ingredients.
• If you have severe breathing problems at rest due to your cancer or if you need oxygen treatment.

Tell your doctor before you use Herceptin

Your doctor will closely supervise your therapy. You should tell your doctor before you use Herceptin:

• If you have had heart failure, coronary artery disease, heart valve disease (heart murmers) or high blood pressure. Talk to your doctor about this because Herceptin can cause heart failure.
• If you suffer from breathlessness. Herceptin can cause breathing difficulties, especially when it is first given. This could be more serious if you are already breathless. Very rarely, patients with severe breathing difficulties before treatment have died when they were given Herceptin.
• If you have ever had chemotherapy with a medicine called doxorubicin or a medicine related to doxorubicin (your doctor can advise you here). These medicinal products can damage heart muscle and increase the risk of heart problems with Herceptin.

If you receive Herceptin with paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient informationackage leaflets for these products

Treatment with Herceptin may affect the heart. Therefore, your heart function will be checked before and during the treatment with Herceptin. If you develop any signs of heart failure (i.e., inadequate pumping of blood by the heart), you may have to stop Herceptin.

Taking other medicines:
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

It may take up to 6 months for Herceptin to be removed from the body. Therefore you should tell your doctor or pharmacist that you have had Herceptin if you start any new medication in the 6 months after stopping treatment

Use in children and adolescents

At present, Herceptin is not recommended for anyone under the age of 18 years because there is not enough information in this age group.

Pregnancy and breast-feeding
Before starting treatment, you must tell your doctor if you are pregnant, if you think you are pregnant or if you intend to become pregnant. You should use effective contraception during treatment with Herceptin and for at least 6 months after treatment has concluded. In rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby within the womb has been observed in pregnant women receiving Herceptin. Your doctor will advise you of the risks and benefits of taking Herceptin during pregnancy.

Do not breast-feed your baby during Herceptin therapy and for 6 months after the last dose of Herceptin.

Ask your doctor or pharmacist for advice before taking any medicine

Driving and using machines
We do not know whether Herceptin could affect your ability to drive a car or operate machines. However, if you experience symptoms, such as chills or fever, during an infusion of Herceptin (see section 4), you should not drive or use machines until these symptoms disappear.

Herceptin is given as an intravenous infusion (?drip?) directly into your veins. The first dose of your treatment is given over 90 minutes and you will be observed by a health professional while it is being given in case you have any side effects. If the first dose is well tolerated the next doses may be given over 30 minutes (see section 2 under ?Tell your doctor before you use Herceptin?).

Before starting the treatment your doctor will determine the amount of HER2 in your tumour. Only patients with a large amount of HER2 will be treated with Herceptin. Your doctor will prescribe a dose and treatment regimen that is right for you . The dose of Herceptin depends on your body weight. The number of infusions you receive will depend on how you respond to the treatment. Your doctor will discuss this with you.

For early breast cancer, metastatic breast cancer and metastatic gastric cancer, Herceptin is given every 3 weeks. Herceptin may also be given once a week for metastatic breast cancer.

Like all medicines, Herceptin can cause side effects, although not everybody gets them. Some of these side effects may be serious and may lead to hospitalisation.

During a Herceptin infusion, chills, fever and other flu like symptoms may occur. These are very common (affects more than 1 user in 10). Other infusion-related symptoms are: feeling sick (nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, wheezing, high or low blood pressure, heart rhythm disturbances (palpitations, heart fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these symptoms can be serious and some patients have died (see 2. under ?Tell your doctor before you use Herceptin?).

These effects mainly occur with the first infusion (?drip? into your vein) and during the first few hours after the start of the infusion. They are usually temporary. You will be observed by a health care professional during the infusion and for at least six hours after the start of the first infusion and for two hours after the start of other infusions. If you develop a reaction, they will slow down or stop the infusion and may give you treatment to counteract the side effects. The infusion may be continued after the symptoms improve.

Occasionally, symptoms start later than six hours after the infusion begins. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then get worse later

Other side effects can occur at any time during treatment with Herceptin, not just related to an infusion. Heart problems can sometimes occur during treatment and occasionally after treatment has stopped and can be serious. They include weakening of the heart muscle possibly leading to heart failure, inflammation (i.e. swollen, red, hot, and in pain) of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as:

• breathlessness (including breathlessness at night),
• cough,
• fluid retention (swelling) in the legs or arms,
• palpitations (heart fluttering or irregular heart beat).

Your doctor will monitor your heart regularly during treatment but you should tell your doctor immediately if you notice any of the above symptoms.

If you experience any of the above symptoms after treatment with Herceptin has been stopped, you should consult your doctor and inform him/ her that you have previously been treated with Herceptin.

Very common side effects of Herceptin(affects more than 1 user in 10) :

• diarrhoea,
• weakness,
• skin rashes,
• chest pain,
• abdominal pain,
• joint pain,
• febrile neutropenia
• and muscle pain.

Other common side effects of Herceptin (affects 1 to 10 users in 100):

• allergic reactions ?itchiness
• abnormal blood counts (anaemia, low ?dry mouth and skin platelet count and low white blood count)
• constipation ?dry or watery eyes
• heartburn (dyspepsia) ?sweating
• infections including bladder and skin ?feeling weak and unwell infections
• shingles ?anxiety
• inflammation of the breast ?depression
• inflammation of the pancreas or liver ?abnormal thinking
• kidney disorders ?dizziness
• increased muscle tone /tension (hypertonia) ?loss of appetite
• tremor ?weight loss
• numbness or tingling of the fingers and toes ?altered taste
• nail disorders ?asthma
• hair loss ?lung disorders
• inability to sleep (insomnia)?back pain
• sleepiness (somnolence) ?neck pain
• nose bleeds ? bone pain
• bruising ?acne
• haemorrhoids ?leg cramps

Other rare side effects of Herceptin, (affects 1 to 10 users in 10,000) are:

• Weakness
• Inflammation/scarring of the lungs
• Jaundice

Other side effects that have been reported with Herceptin use (frequency cannot be estimated from the available data):

• Abnormally low clotting factor
• Anaphylactic reactions
• High potassium levels
• Swelling of the brain
• Swelling /bleeding at the back of the eyes
• Shock
• Swelling of the lining of the heart
• Slow heart rate
• Abnormal heart rhythm
• Respiratory distress
• Respiratory Failure
• Acute accumulation of fluid in the lungs
• Acute narrowing of the airways
• Abnormally low oxygen levels in the blood
• Swelling of the throat
• Difficulty in breathing when lying flat
• Liver damage/failure
• Swelling of the face,lips and throat
• rash (itchy, bumpy)
• Kidney damage/ failure
• Abnormally low levels of fluid around baby in womb

Some of the side effects you experience may be due to your underlying breast cancer. If you receive Herceptin in combination with chemotherapy, some of them may also be due to the chemotherapy.

If you experience any of the side effects mentioned in this leaflet or notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use this medicine after the expiry date which is stated on the outer carton and on the vial label after EXP.

Store in a refrigerator (2°C ? 8°C).

Infusion solutions should be used immediately after dilution. Do not use Herceptin if you notice any particulate matter or discoloration prior to administration.

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 Herceptin contains

• The active substance is trastuzumab. Each vial contains 150 mg trastuzumab that has to be dissolved in 7.2 ml of water for injection. The resulting solution contains approximately 21 mg/ml trastuzumab.
• The other ingredient(s) are L-histidine hydrochloride, L-histidine, ?,?-trehalose dihydrate, polysorbate 20.

What Herceptin looks like and contents of the pack

Herceptin is a powder for concentrate for solution for infusion, that is supplied in a glass vial with a rubber stopper containing 150 mg of trastuzumab. The powder is a white to pale yellow pellet. Each carton contains 1 vial of powder..

Marketing Authorisation Holder

Roche Registration Limited
6 Falcon Way

Shire Park
Welwyn Garden City
AL7 1TW
United Kingdom

Manufacturer

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

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

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This leaflet was last approved in

The following information is intended for medical or healthcare professionals only

Always keep this medicine in the closed original pack at a temperature of 2ºC ? 8 ºC in a refrigerator. A vial of Herceptin reconstituted with water for injections (not supplied) is stable for 48 hours at 2ºC ? 8 ºC after reconstitution and must not be frozen.

Appropriate aseptic technique should be used. Each vial of Herceptin is reconstituted with 7.2 ml of water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields a 7.4 ml solution for single-dose use, containing approximately 21 mg/ml trastuzumab. A volume overage of 4 % ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Herceptin should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted Herceptin may result in problems with the amount of Herceptin that can be withdrawn from the vial.

Instructions for Reconstitution:
1) Using a sterile syringe, slowly inject 7.2 ml of water for injections in the vial containing the lyophilised Herceptin, directing the stream into the lyophilised cake.
2) Swirl vial gently to aid reconstitution. DO NOT SHAKE!

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed for approximately 5 minutes. The reconstituted Herceptin results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.

Determine the volume of the solution required:

• based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose of 2 mg trastuzumab/kg body weight:

Volume (ml) = Body weight(kg) xdose(4mg/kg for loading or2mg/kg for maintenance)21 (mg/ml, concentration of reconstituted solution)

• based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly dose of 6 mg trastuzumab/kg body weight:

Volume (ml) = Body weight(kg) xdose(8mg/kg for loading or 6 mg/kg for maintenance)21 (mg/ml, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial and added to a polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 ml of 0.9 % sodium chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to mix the solution in order to avoid foaming. Parenteral solutions should be inspected visually for particulates and discoloration prior to administration. Once the infusion is prepared it should be administered immediately. If diluted aseptically, it may be stored for 24 hours (do not store above 30°C).