Ogivri

Package leaflet: Information for the user

Ogivri 150 mg powder for concentrate for solution for infusion, 420 mg powder for concentrate for solution for infusion

trastuzumab
Please read all of this leaflet carefully before you start 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.
• If you get 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 Ogivri is and what it is used for
2. What you need to know before you are given Ogivri
3. How Ogivri is given
4. Possible side effects
5. How to store Ogivri
6. Contents of the pack and other information

1. What Ogivri is and what it is used for

Ogivri contains the active substance trastuzumab, which is a monoclonal antibody.
Monoclonal antibodies bind to specific proteins or antigens. Trastuzumab is designed to bind
selectively to an antigen called human epidermal growth factor receptor 2 (HER2).
HER2 is present in large amounts on the surface of certain tumour cells and stimulates their growth.
When Ogivri binds to HER2, it blocks the growth of these cells and causes their death.
Your doctor may prescribe Ogivri for the treatment of breast and gastric cancer if:

• you have early-stage breast cancer with high levels of a protein called HER2.
• you have metastatic breast cancer (breast cancer that has spread away from the primary tumour) with high levels of HER2. Ogivri may be prescribed in combination with the chemotherapeutic medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer, or it may be prescribed alone when other treatments have proven ineffective. It is also used in combination with medicines called aromatase inhibitors for the treatment of patients with high levels of HER2 and metastatic breast cancer with hormone receptor-positive (cancer that is sensitive to female sex hormones).
• you have metastatic gastric cancer with high levels of HER2, in combination with other anticancer medicines, capecitabine or 5-fluorouracil and cisplatin.

2. What you should know before being given Ogivri

Do not use Ogivri:

• if you are allergic to trastuzumab, mouse (murine) proteins, or any of the excipients in this medicine (listed in section 6).
• if you have severe resting respiratory problems due to your tumour or require oxygen therapy.

Warnings and precautions
Your doctor will closely monitor you during treatment.
Heart checks
Treatment with Ogivri, either alone or in combination with a taxane, may affect the heart,
particularly if you have previously received an anthracycline (taxanes and anthracyclines are two other types of medicines
used to treat tumours).
These effects may range from moderate to severe and may be life-threatening. Your heart function will therefore be checked before, during (every three months), and after (up to two to five years) treatment with Ogivri. If you develop signs of heart failure (i.e. the heart's inability to pump blood adequately), you may require more frequent monitoring of heart function (every six to eight weeks), may be given treatment for heart failure, or may need to stop treatment with Ogivri.
Talk to your doctor, pharmacist, or nurse before being given Ogivri if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, or if you have taken or are currently taking any medicine to treat high blood pressure.
• you have taken or are currently taking a medicine called doxorubicin or epirubicin (medicines used to treat tumours). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems when taking Ogivri.
• you suffer from shortness of breath, especially if you are currently receiving a taxane. Ogivri may cause difficulty breathing, particularly the first time it is administered. This may be more serious if you already have breathing difficulties. Very rarely, patients with severe breathing difficulties before treatment have died after receiving Ogivri.
• you have received other cancer treatments.

If you are receiving Ogivri in combination with any other medicine used to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5­fluorouracil, or cisplatin, you should also read the package leaflet for these medicines.
Children and adolescents
Ogivri is not recommended for individuals under 18 years of age.
Other medicines and Ogivri
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
It may take up to 7 months for Ogivri to be eliminated from your body. Therefore, you must tell your doctor, pharmacist, or nurse that you have been given Ogivri if you start taking any new medicine within 7 months after stopping treatment.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning a pregnancy, inform your doctor, pharmacist, or nurse before taking this medicine.
Pregnancy

• You must use effective contraception during treatment with Ogivri and for at least 7 months after the end of treatment.
• Your doctor will discuss with you the risks and benefits of taking Ogivri during pregnancy. In rare cases, women treated with trastuzumab during pregnancy have experienced reduced levels of amniotic fluid surrounding the developing baby in the womb. This
  condition may be harmful to the unborn baby and has been associated with incomplete lung maturation, which has led to fetal death.
  Breastfeeding
  Do not breastfeed during treatment with Ogivri and for 7 months after the last dose of Ogivri, as the medicine may pass into breast milk.
  Ask your doctor or pharmacist for advice before taking any medicine.
  Driving and using machines
  Ogivri may affect your ability to drive or operate machinery. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, you should not drive or use machinery until these symptoms resolve.
  Ogivri contains sorbitol (E420) and sodium
  Ogivri 150 mg powder for concentrate for solution for infusion
  This medicine contains 115.2 mg of sorbitol per vial.
  Ogivri 420 mg powder for concentrate for solution for infusion
  This medicine contains 322.6 mg of sorbitol per vial.
  Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, this medicine must not be administered to you. Patients with HFI are unable to metabolize fructose, which may cause serious adverse effects.
  Inform your doctor before receiving this medicine if you have HFI or if you can no longer consume sugary drinks or foods because they cause discomfort, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhoea.
  Ogivri contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How Ogivri is administered

Before starting treatment, your doctor will determine the amount of HER2 in the tumour. Only patients with high levels of HER2 will be treated with Ogivri. Ogivri must be administered only by a doctor or a nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you. The dose of Ogivri depends on your body weight.

The first dose of treatment will be given over a period of 90 minutes, and you will be monitored by a healthcare professional during the infusion in case you experience any side effects. If the first dose is well tolerated, subsequent doses may be administered over a period of 30 minutes (see section 2 “Warnings and precautions”). The number of infusions you will receive depends on your response to treatment. Your doctor will discuss this with you.

Ogivri is given as an infusion directly into the vein (intravenous infusion). This intravenous formulation is not intended for subcutaneous administration and must be administered solely via intravenous infusion.

In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Ogivri is administered every 3 weeks. Ogivri may also be administered once a week for the treatment of metastatic breast cancer.

To prevent medication errors, it is important to check the vial labels to ensure that the medicine being prepared and administered is Ogivri (trastuzumab) and not another trastuzumab-containing medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

If you interrupt treatment with Ogivri
Do not stop taking this medicine without first talking to your doctor. All doses must be taken at the correct time, either weekly or every three weeks (depending on your treatment schedule). This helps the medicine work most effectively.

It may take up to 7 months for Ogivri to be eliminated from the body. Therefore, your doctor may decide to continue monitoring heart function even after treatment has ended.

If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of these side effects can be serious and may require hospitalisation.
During infusion of Ogivri, reactions such as chills, fever and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people).
Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), facial or lip swelling, skin rashes and feeling of fatigue. Some of these symptoms may be severe, and some patients have died (see section 2 “Warnings and precautions”).
These effects occur mainly with the first intravenous infusion (“drip” into the vein) and during the first few hours after the start of the infusion. They are usually temporary. You will be monitored by a healthcare 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 subsequent infusions. If you experience a reaction, the infusion will be slowed down or stopped, and you may be given treatment to counteract the side effects. The infusion may be resumed once symptoms have improved.
Occasionally, symptoms may begin more than six hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes symptoms may improve and then worsen again later.

Serious side effects
Other serious side effects may occur at any time during treatment with Ogivri, not only in relation to an infusion. Inform your doctor or nurse immediately if you notice any of the following side effects:

• Heart problems, which may sometimes be serious, can occur during treatment and occasionally after treatment has been stopped. These include weakening of the heart muscle, which may lead to heart failure, inflammation of the lining of the heart, and heart rhythm disorders. These may cause symptoms such as shortness of breath (including at night), cough, fluid retention (swelling) in the legs or arms, and palpitations (rapid or irregular heartbeat) (see Heart monitoring in section 2).
  Your doctor will monitor your heart regularly during and after treatment, but you must inform your doctor immediately if you notice any of the symptoms listed above.

• Tumour lysis syndrome (a group of metabolic complications occurring after anti-tumour treatment, characterised by high levels of potassium and phosphate in the blood and low levels of calcium in the blood). Symptoms may include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (rapid or slow heartbeat), seizures, vomiting or diarrhoea, and tingling around the mouth, hands or feet.
  If you experience any of the above symptoms after completing treatment with Ogivri, you must see a doctor and inform them about your previous treatment with Ogivri.

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

• infections
• diarrhoea
• constipation
• chest burning (dyspepsia)
• fatigue
• skin rash
• chest pain
• abdominal (stomach) pain
• joint pain
• low red and white blood cell counts (which help fight infections), sometimes associated with fever
• muscle pain
• conjunctivitis (itchy, discharging eyes and crusts on eyelids)
• excessive tearing
• nosebleeds
• runny nose
• hair loss
• tremor
• hot flushes
• dizziness
• nail problems
• weight loss
• loss of appetite
• inability to sleep (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling in fingers and toes, occasionally extending to the rest of the limb
• redness, swelling or blisters in the mouth and/or throat
• pain, swelling, redness or numbness in hands and/or feet
• shortness of breath
• headache
• cough
• vomiting
• nausea (feeling unwell)

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

• allergic reactions
• dry mouth and dry skin
• throat infections
• dry eyes
• bladder and skin infections
• sweating
• fatigue and malaise
• sinus inflammation
• anxiety
• liver inflammation
• depression
• kidney disorders
• increased muscle tone or tension (hypertonia)
• asthma
• lung infection
• pain in arms and/or legs
• lung disorders
• itchy skin rash
• back pain
• drowsiness
• neck pain
• haemorrhoids (swelling of blood vessels around the anus)
• bone pain
• itching
• acne
• leg cramps

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

• deafness
• skin rash with wheals
• wheezing
• lung inflammation or scarring (fibrosis)

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

• jaundice (yellowing of the skin and whites of the eyes)
• anaphylactic reactions (severe sudden allergic reactions with symptoms such as rash, itching, breathing difficulties, dizziness or fainting)

Side effects with unknown frequency (frequency cannot be estimated from available data):

• blood clotting abnormalities or changes
• high potassium levels
• swelling or bleeding behind the eyes
• shock (a dangerous drop in blood pressure causing symptoms such as rapid, shallow breathing, cold clammy skin, weak pulse, dizziness, malaise and fainting)
• abnormal heart rhythm
• respiratory distress
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low levels of oxygen in the blood
• difficulty breathing when lying down
• liver damage
• swelling of the face, lips and throat
• kidney failure
• abnormally low levels of fluid around the unborn baby in the womb
• inadequate development of the unborn baby’s lungs
• abnormal development of the unborn baby’s kidneys

Some of the side effects experienced may be due to breast cancer. If you are receiving Ogivri in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.

Reporting of side effects
If you get any side effects, including ones 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 Ogivri

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the vial after “Exp”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Infusion solutions should be used immediately after dilution. Do not use Ogivri if, before administration, you notice particles or any change in colour.
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 Ogivri contains

• The active substance is trastuzumab. Each vial contains: either 150 mg of trastuzumab to be dissolved in 7.2 mL of water for injections, or 420 mg of trastuzumab to be dissolved in 20 mL of water for injections.
• The resulting solution contains approximately 21 mg/mL of trastuzumab.
• The other components are L-histidine hydrochloride, L-histidine, sorbitol (E420 [see section 2 "Ogivri contains sorbitol (E420) and sodium"]), macrogol 3350, hydrochloric acid and sodium hydroxide (for pH adjustment).

Description of the appearance of Ogivri and contents of the pack
Ogivri is a powder for concentrate for solution for intravenous infusion supplied in a glass vial sealed with a rubber stopper containing either 150 mg or 420 mg of trastuzumab. The powder is a white to pale yellow pellet. Each pack contains 1 vial of powder.
Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
Ireland
D13 R20R
Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
Ireland
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Biocon Biologics Belgium BV Biosimilar Collaborations Ireland Limited
Tél/Tel: 0080008250910 Tel: 0080008250910
България Luxembourg/Luxemburg
Biosimilar Collaborations Ireland Limited Biocon Biologics France S.A.S
Тел: 0080008250910 Tél/Tel: 0080008250910
Česká republika Magyarország
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel.: 0080008250910
Danmark Malta
Biocon Biologics Finland OY Biosimilar Collaborations Ireland Limited
Tlf: 0080008250910 Tel.: 0080008250910
Deutschland Nederland
Biocon Biologics Germany GmbH Biocon Biologics France S.A.S
Tel: 0080008250910 Tel: 0080008250910
Eesti Norge
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Tel: 0080008250910 Tlf: +47 800 62 671
Ελλάδα Österreich
Biocon Biologics Greece ΜΟΝΟΠΡΟΣΩΠΗ Biocon Biologics Germany GmbH
Ι.Κ.Ε Tel: 0080008250910
Τηλ.: 0080008250910
España Polska
Biocon Biologics Spain S.L. Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910
France Portugal
Biocon Biologics France S.A.S Biocon Biologics Spain S.L.
Tel: 0080008250910 Tel: 0080008250910
Hrvatska România
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910
Ireland Slovenija
Biosimilar Collaborations Ireland Limited Biosimilar Collaborations Ireland Limited
Tel: 1800 777 794 Tel: 0080008250910
Ísland Slovenská republika
Biocon Biologics Finland OY Biocon Biologics Germany GmbH
Sími: +345 8004316 Tel: 0080008250910
Italia Suomi/Finland
Biocon Biologics Spain S.L. Biocon Biologics Finland OY
Tel: 0080008250910 Puh/Tel: 99980008250910
Κύπρος Sverige
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Τηλ: 0080008250910 Tel: 0080008250910
Latvija
Biosimilar Collaborations Ireland Limited
Tel: 0080008250910
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu .

The following information is intended for healthcare professionals only

To avoid medication administration errors and to ensure that the drug being prepared and administered is Ogivri (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is essential to check the vial label.
Store the medicinal product in its original closed packaging in a refrigerator at 2 °C – 8 °C. A vial of Ogivri reconstituted aseptically with sterile water for injections (not supplied) remains stable for 10 days at 2 °C – 8 °C after reconstitution and must not be frozen.
Ogivri must be handled carefully during the reconstitution process. Excessive foaming occurring during reconstitution or agitation of the reconstituted Ogivri solution may lead to difficulties in withdrawing the intended amount of Ogivri from the vial.

Ogivri 150 mg powder for concentrate for solution for infusion
Follow appropriate aseptic techniques. Each 150 mg vial of Ogivri is reconstituted with 7.2 mL of sterile water for injections (not supplied). Avoid using other solvents for reconstitution. This yields 7.4 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. An overfill of 4% ensures that the intended dose of 150 mg can be withdrawn from the vial.

Ogivri 420 mg powder for concentrate for solution for infusion
Follow appropriate aseptic techniques. Each 420 mg vial of Ogivri is reconstituted with 20 mL of sterile water for injections (not supplied). Avoid using other solvents for reconstitution. This yields 21 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. An overfill of 4.8% ensures that the intended dose of 420 mg can be withdrawn from the vial.

Instructions for Reconstitution

1. Using a sterile syringe, slowly inject the appropriate volume (as indicated above) of water for
   injections into the vial containing Ogivri lyophilisate, directing the stream towards the lyophilized
   powder.
2. Gently rotate the vial to facilitate reconstitution. DO NOT SHAKE!
   Slight foaming during reconstitution is not unusual. Allow the vial to stand in an upright position for
   approximately 5 minutes. Once reconstituted, Ogivri appears as a clear, colourless to pale yellow
   solution, free from visible particles.

Determine the volume of solution required:

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

Body Weight (kg) × dose ( 4 mg/kg for loading dose or 2 mg/kg for maintenance dose)
Volume (mL) =
21 (mg/mL, concentration of reconstituted solution)

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

Body Weight (kg) × dose ( 8 mg/kg for loading dose or 6 mg/kg for maintenance dose)
Volume (mL) =
21 (mg/mL, concentration of reconstituted solution)

Withdraw the required amount of solution from the vial using a sterile needle and syringe and transfer it
into a polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 mL of 9 mg/mL
(0.9%) sodium chloride solution. Do not use glucose-containing solutions. The bag should be gently
inverted to mix the solution, avoiding foam formation. Parenteral solutions should be visually
inspected for particulate matter and discoloration prior to administration. Once prepared, the infusion
should be administered immediately. If aseptically diluted, it may be stored for up to 90 days at 2°C –
8°C and for 24 hours at temperatures not exceeding 30°C.