Patient leaflet - Zercepac 60 mg powder for concentrate for solution for infusion

1. What Zercepac is and what it is used for

Zercepac 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 receptor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates their growth. When Zercepac binds to HER2 it stops the growth of such cells and causes them to die.

Your doctor may prescribe Zercepac 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 (breast cancer that has spread
beyond the original tumour) with high levels of HER2. Zercepac may be prescribed in combination with the chemotherapy medicine 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 (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.

2. What you need to know before you are given Zercepac

Do not use Zercepac if

you are allergic to trastuzumab, to murine (mouse) proteins, or to
any of the other ingredients of this medicine (listed in section 6).
you have severe breathing problems at rest due to your cancer or if
you need oxygen treatment.

Warnings and precautions

Your doctor will closely supervise your therapy.

Heart checks

Treatment with Zercepac alone or with a taxane may affect the heart, especially if you have ever used an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer). The effects may be moderate to severe and could cause death. Therefore, your heart function will be checked before, during (every three months) and after (up to two to five years) treatment with Zercepac. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your heart function may be checked more frequently (every six to eight weeks), you may receive treatment for heart failure or you may have to stop Zercepac treatment.

Talk to your doctor, pharmacist or nurse before you are given Zercepac if:

you have had heart failure, coronary artery disease, heart valve
disease (heart murmurs), high blood pressure, taken any high blood pressure medicine or are currently taking any high blood pressure medicine.
you have ever had or are currently using a medicine called
doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle and increase the risk of heart problems with Zercepac.
you suffer from breathlessness., especially if you are currently using
a taxane. Zercepac 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 Zercepac.
you have ever had any other treatment for cancer.

If you receive Zercepac with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient information

leaflets for these products.

Children and adolescents

Zercepac is not recommended for anyone under the age of 18 years.

Other medicines and Zercepac

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or may take any other medicines.

It may take up to 7 months for Zercepac to be removed from the body. Therefore you should tell your doctor, pharmacist or nurse that you have had Zercepac if you start any new medicine in the 7 months after stopping treatment.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before taking this medicine.
You should use effective contraception during treatment with
Zercepac and for at least 7 months after treatment has ended.
Your doctor will advise you of the risks and benefits of taking
Zercepac during pregnancy. 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 Zercepac. This condition may be harmful to your baby in the womb and has been associated with the lungs not developing fully resulting in foetal death.

Do not breast-feed your baby during Zercepac therapy and for 7 months after the last dose of Zercepac as Zercepac may pass to your baby through your breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Zercepac may affect your ability to drive a car or operate machines. If during treatment you experience symptoms, such as dizziness, sleepiness, chills or fever, you should not drive or use machines until these symptoms disappear.

Sodium

Zercepac contains less than 1 mmol of sodium per dose, i.e. it is essentially sodium-free.

Polysorbate 20

Zercepac contains 0.24 mg of polysorbate 20 in each 60 mg vial, which is equivalent to 0.08 mg/mL (after reconstitution with 3.0 mL sterile water for injection).

Zercepac contains 0.6 mg of polysorbate 20 in each 150 mg vial, which is equivalent to 0.083 mg/mL (after reconstitution with 7.2 mL sterile water for injection).

Zercepac contains 1.7 mg of polysorbate 20 in each 420 mg vial, which is equivalent to 0.085 mg/mL (after reconstitution with 20.0 mL sterile water for injection).

Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

3. How Zercepac is given

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 Zercepac. Zercepac should only be given by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is right for you. The dose of Zercepac depends on your body weight.

Zercepac intravenous formulation 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 “Warnings and precautions”). The number of infusions you receive will depend on how you respond to the treatment. Your doctor will discuss this with you.

In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Zercepac (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

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

If you stop using Zercepac

Do not stop using this medicine without talking to your doctor first. All doses should be taken at the right time every week or every three weeks (depending on your dosing schedule). This helps your medicine work as well as it can.

It may take up to 7 months for Zercepac to be removed from your body. Therefore your doctor may decide to continue to check your heart functions, even after you finish treatment.

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

4. Possible side effects

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

Serious side effects

During a Zercepac infusion, chills, fever and other flu like symptoms may occur. These are very common (may affect more than 1 in 10 people). Other infusion-related symptoms are: feeling sick (nausea),

The following information is intended for medical or healthcare professionals only

Zercepac is provided in sterile, preservative-free, non-pyrogenic, single use vials.

Always keep this medicine in the closed original pack at a temperature of 2ºC - 8ºC in a refrigerator.

Since the medicinal product does not contain any anti-microbial preservative or bacteriostatic agents, appropriate aseptic technique should be used for reconstitution and dilution procedures. Care must be taken to ensure the sterility of prepared solutions.

A vial of Zercepac aseptically reconstituted with sterile water for injections (not supplied) is chemically and physically stable for 48 hours at 2ºC - 8ºC after reconstitution and must not be frozen.

After aseptic dilution in polyethylene or polypropylene bags containing sodium chloride 9 mg/mL (0.9%) solution for injection, chemical and physical stability of Zercepac has been demonstrated for up to 84 days at 2°C - 8°C, 7 days at 23°C - 27°C and 24 hours at 30°C.

From a microbiological point of view, the reconstituted solution and Zercepac infusion solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.

Aseptic preparation, handling and storage:

The infusion preparation should be:

performed by trained personnel in accordance with good practice rules especially with respect to the aseptic preparation of parenteral products.
prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
followed by adequate storage of the prepared solution for intravenous infusion to ensure maintenance of the aseptic conditions. Instructions for aseptic reconstitution:
Using a sterile syringe, slowly inject the appropriate volume
(as noted below) of sterile water for injections (not supplied) in the vial containing the lyophilised Zercepac, directing the stream into the lyophilised cake. Use of other reconstitution solvents should be avoided.
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 Zercepac results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.

Zercepac 60 mg powder for concentrate for solution for infusion Reconstitution of the 60 mg vial with 3.0 mL of sterile water for injections yields a 3.1 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 8% ensures that the labelled dose of 60 mg can be withdrawn from each vial.

Zercepac 150 mg powder for concentrate for solution for infusion Reconstitution of the 150 mg vial with 7.2 mL of sterile water for injections yields a 7.5 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 5% ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Zercepac 420 mg powder for concentrate for solution for infusion Reconstitution of the 420 mg vial with 20.0 mL of sterile water for injection yields a 20.6 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 3% ensures that the labelled dose of 420 mg can be withdrawn from each vial.

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

Instructions for aseptic dilution of the reconstituted solution 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) x dose (4 mg/kg for loading or 2 mg/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) x dose (8 mg/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 using a sterile needle and syringe and added to a polyethylene or polypropylene infusion bag containing 250 mL of 9 mg/ml (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.

vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, 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 section 2 under “Warnings and precautions”).

These effects mainly occur with the first intravenous 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 serious side effects can occur at any time during treatment with Zercepac, not just related to an infusion. Tell a doctor or nurse straight away, if you notice any of the following side effects:

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 (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) (see section 2. Heart checks).

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

Tumour lysis syndrome (a group of metabolic complications
occurring after cancer treatment characterized by high blood levels of potassium and phosphate, and low blood levels of calcium). Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion), heart problems (fluttering of the heart or a faster or slower heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet.

If you experience any of the above symptoms when your treatment with Zercepac has finished, you should see your doctor and tell them that you have previously been treated with Zercepac.

Other side effects

Very common side effects: may affect more than 1 in 10 people

infections
diarrhoea
constipation
heartburn (dyspepsia)
fatigue
skin rashes
chest pain
abdominal pain
joint pain
low counts of red blood cells and white blood cells (which help fight
infection) sometimes with fever
muscle pain
conjunctivitis
watery eyes
nose bleeds
runny nose
hair loss
tremor
hot flush
dizziness
nail disorders
weight loss
loss of appetite
inability to sleep (insomnia)
altered taste
low platelet count
bruising
numbness or tingling of the fingers and toes, which occasionally
may extend to the rest of the limb
redness, swelling or sores in your mouth and/or throat
pain, swelling, redness or tingling of hands and/or feet
breathlessness
headache
cough
vomiting
nausea

Common side effects: may affect up to 1 in 10 people

allergic reactions
throat infections
bladder and skin infections
inflammation of the breast
inflammation of the liver
kidney disorders
increased muscle tone or tension (hypertonia)
pain in the arms and/or legs
itchy rash
sleepiness (somnolence)
haemorrhoids
itchiness
dry mouth and skin
dry eyes
sweating
feeling weak and unwell
anxiety
depression
asthma
infection of lungs
lung disorders
back pain
neck pain
- bone pain
- acne
- leg cramps

Uncommon side effects: may affect up to 1 in 100 people:

deafness
bumpy rash
wheezing
inflammation or scarring of the lungs

Rare side effects: may affect up to 1 in 1000 people

jaundice
anaphylactic reactions

Side effects of unknown frequency: frequency cannot be estimated from the available data

abnormal or impaired blood clotting
high potassium levels
swelling or bleeding at the back of the eyes
shock
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
difficulty in breathing when lying flat
liver damage
swelling of the face, lips and throat
kidney failure
abnormally low levels of fluid around baby in womb
failure of the lungs of the baby to develop in the womb
abnormal development of the kidneys of the baby in the womb

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

If you get any side effects, talk to your doctor, pharmacist or nurse.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Zercepac

Zercepac will be stored by the health professionals at the hospital or clinic.

Keep this medicine out of the sight and reach 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. The expiry date refers to the last day of that month.
The unopened vial should be stored in a refrigerator (2°C-8°C).
Do not freeze the reconstituted solution.
Infusion solutions should be used immediately after dilution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Do not use Zercepac 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.

6. Contents of the pack and other information

What Zercepac contains

The active substance is trastuzumab. Each vial contains either:

60 mg trastuzumab that has to be dissolved in 3.0 mL of sterile water for injections.
150 mg trastuzumab that has to be dissolved in 7.2 mL of sterile water for injection or
420 mg trastuzumab that has to be dissolved in 20.0 mL of sterile water for injection
The resulting solution contains approximately 21 mg/mL trastuzumab.
The other ingredient(s) are L-histidine hydrochloride monohydrate,
L-histidine, α,α-trehalose dihydrate, polysorbate 20 (E432) (see section 2 “Polysorbate 20”).

What Zercepac looks like and contents of the pack

Zercepac is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass vial with a rubber stopper containing 60 mg, 150 mg or 420 mg of trastuzumab. The powder is a white to pale yellow pellet. Each carton contains 1 vial of powder.

Marketing Authorisation Holder

Accord Healthcare Limited

Sage House, 319 Pinner Road

North Harrow, Middlesex, HA1 4HF

United Kingdom

Manufacturer

Accord Healthcare Polska Sp. z.o.o

ul Lutomierska 50, 95-200 Pabianice

Poland