InfoCons Consumer Protection informs you – Ogivri – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start using this medicine beca use it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse .
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet . See section 4.

ℹ️ 1. What Ogivri is and what it is used for

Ogivri contains the active substance trastuz umab, which is a monoclonal antibody. Monoclonal antibodies attach to specific proteins or antigens. Trastuz umab is designed to bind selectively to an antigen called human epide rmal growth factor recept or 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stim ulates their growth. When Ogivri binds to HER2 it stops the growth of such cells and causes them to die.

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

• You have early breast cancer, with high levels of a protein called HER2.
• Yo u have me tastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Ogivri may be pr escribed in combination with the chemotherap y medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccess ful. It is also used in combination with med icines called aromat ase inhibitors with patients with high levels of HER2 and ho rmone receptor -positive metas tatic breast cancer (cancer that is sensitive to the presence of female sex horm ones).
• You have me tastatic gastr ic cancer with high levels of HER2, when it is in combination with the other cancer medicines capecitabine or 5- fluorouracil and cisplatin.

⚠️ 2. What you need to know before you are given Ogivri

Do not use Ogivri

• if you are allergic to trastuzumab, murine (mouse) proteins, or any of the other ingredients of this medicine (listed in section 6).
• if 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 Ogivri alone or with a taxane m ay affect the hea rt, especially if you have ever used an anthrac ycline (taxanes and anthra cyclines are two other kinds of medicine used to treat cancer).

The effects may be m oderate to severe and could cause death. Therefore, your he art function will be checked before, during (every three months) and af ter (up to two to five years) treatment with Ogivri.

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 m ay have to stop Ogivri treatment.

Talk to your doctor, pharmacist or nur se before you are given Ogivri if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murm urs), high blood pressure, taken any high blood pressure medic ine or are current ly taking any high blood pressure medicine.
• you have ever had or are current ly using a m edicine called doxorub icin or epiru bicin (medicines used to treat cancer). These medicines (or any other anthracycline s) can damage heart muscle and increase the risk of heart problems w ith Ogivri.
• you suffer from breathless ness, especial ly if you are current ly using a taxane. Ogivri can cause breath ing difficultie s, 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 Ogivri.
• you have ever had any o ther treatment for cancer.

If you receive Ogivri wi th any other medicine to treat cancer, such as paclita xel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluor ouracil, or cisplatin you should also read the patient infor mation leaflets for these products.

Children and adolescents

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

Other medicines and Ogivri

Tell your doctor, pharm acist 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 removed from the body. Therefore , you should tell your doctor, pharmacist or nur se that you have had Ogivri if you start any new medicine in the 7 months after stopping treatment.

Pr egnancy and breast -feeding If you are pregnant or breast -feeding , think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before taking this medicine.

Pregnancy

• You should use effective contraception during treatment with Ogivri and for at least 7 months after treatment has ended.
• Your doctor will advise you of the risks and benefits of taking Ogivri 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 trastuzumab . This 51 condition may be harmful to your baby in the womb and has been associated with the lungs not developing fully resulting in foetal death.

Breast -feeding Do not breast -feed your ba by during Ogivri therapy and for 7 months after the last dose of Ogivri as this medicine may pass to your baby through your breast milk. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Ogivri 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.

Ogivri contains sorbitol (E420) and s odium

Ogivri 150 mg powder for concentrate for solution for infusion.

This medicine contains 115.2 mg sorbitol in each vial.

Ogivri 420 mg powder for concentrate for solution for infusion.

This medicine contains 322.6 mg sorbitol in each vial.

Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, you must not r eceive this medicine. Patients with HFI cannot break down fructose, which may cause serious side effects.

You must tell your doctor before receiving this medicine if you have HFI or if you can no longer take sweet foods or drinks because you feel sick, vomit or get unpleasant ef fects such as bloating, stomach cramps or diarrhoea.

Ogivri contains less than 1 mmol sodium (23 mg) per dose , that is to say essentially ‘sodium free ’.

💊 3. H ow Ogivri is given

Before starti ng the treatment your doctor will determine the amount of HER2 in your tum our. Only patients with a large amou nt of HER2 will be treated with Ogivri. Ogivri 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 Ogivri depends on your body weight.

The first dose of your treatment is given over 90 m inutes and you w ill 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 m ay be given over 30 minutes (see section 2 under “ Warnings and precautions”). The number of infusions you receive will depend on how you respond t o the treatment. Your doct or will discuss this with you.

Ogivri is given as an infusion into a vein (intravenous infusion , drip) , this intravenous formulation is not for subcutaneous use and should be given as an intravenous infusion only.

For early breast cancer, metastat ic bre ast cancer and metastatic gastric cancer, Ogivri is given every 3 weeks. Ogivri may also be given once a week for meta static breast cancer.

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

52 If you stop using Ogivri 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 (dependi ng on your dosing schedule). This helps your medicine work as well as it can.

It may take up to 7 months for Ogivri 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, this medicine can cause side effects, although not everybody gets them.

Some of these side effec ts may be serious and may lead to hospitalisation.

During an Ogivri 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), 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), swell ing 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 (“dri p” 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 infusion s. 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.

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

Serious side effects

Other side effects can occur at any time during treatment with Ogivri, not just related to an infusion.

Tell a doctor or nurse straight away, if you notice any of the following side effects:

• Heart proble ms can somet imes 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 of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as breathlessnes s (including breathlessn ess at night), cough, fluid retention (swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see “Heart checks” in section 2) .

Your doctor will monitor your heart regular ly during and after treatment but you shoul d tell your doctor immediately if you notice any of the above sympto ms.

• Tumour lysis syndrome (a group of metabolic complications occurring after cancer treatment characterised 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 o r a faster or slower heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet.

53 If you experience any of the above sympto ms when your treatment with Ogivri has finished, you should see your doctor and tell them that you have previous ly been treated with Ogivri.

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

• infections
• diarrhoea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rashes
• chest pain
• abdominal (stomach) pain
• joint pain
• low counts of red blood cells and white blood cells (which help fight infection) sometimes with fever
• muscle pain
• conjunctivitis (discharge with itching of the eyes and crusty eyelids)
• watery eyes
• nose bleeds
• runny nose
• hair loss
• tremor
• hot flush
• dizziness
• nail disorders
• weight loss
• loss of appetite
• inabili ty to sleep (inso mnia)
• 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 (feeling sick)

Common side effects (may affect up to 1 in 1 0 peo ple)

• allergic reactions
• dry mouth and skin
• throat infections
• dry eyes
• bladder and skin infections
• sweating
• feeling weak and unwell
• inflammation of the breast
• anxiety
• inflammation of the liver 54 • depression
• kidney disord ers
• increased muscle tone or tension (hypertonia)
• asthma
• infection of lungs
• pain in the arms and/or legs
• lung disorders
• itchy rash
• back pain
• sleepiness (somnolence)
• neck pain
• haemorrhoids (swelling of blood vessels around the back passage)
• bone pain
• itchiness
• 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 1 000 people )

• jaundice (yellowing of the skin and the whites of the eyes)
• anaphylactic reactions (serious sudden allergic reaction with symptoms such as rash, itchy skin, difficulty breathing or feeling dizzy or faint) Side effects of not known 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 (a dangerous decrease of blood pressure causing symptoms like rapid, shallow breathing, cold, clammy skin, a rapid, weak pulse, dizziness, weakness and fainting)
• abnormal heart rhythm
• respiratory distr ess
• 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 lungs to develop in the womb
• abnormal kidney development in the womb Some of the side effects you experience may be due to your underl ying breast cancer. If you receive Ogivri in combination with chemotherap y, some of them may also be due to the chemotherap y.

Reporting of side effects

55 If you get any side effects, talk to your doctor, pharm acist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national repor ting system listed in Appendix V . By repor ting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. H ow to store Ogivri

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.

Store in a refrigerator (2 °C – 8 °C).

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use . These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Ogivri contains

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

What Ogivri looks like and contents of the pack

Ogivri is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass vial with a rubber stopper containing either 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

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 56 Dublin D09 C6X8 Ireland For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Biocon Biologics Belgium BV Tél/Tel: 0080008250910 Lietuva Biosimilar Collaborations Ireland Limited Tel: 0080008250910 България Biosimilar Collaborations Ireland Limited Тел: 0080008250910 Luxembourg/Luxemburg Biocon Biologics France S.A.S Tél/Tel: 0080008250910 Česká republika Biocon Biologics Germany GmbH Tel: 0080008250910 Magyarország Biosimilar Collaborations Ireland Limited Tel.: 0080008250910 Danmark Biocon Biologics Finland OY Tlf: 0080008250910 Malta Biosimilar Collaborations Ireland Limited Tel.: 0080008250910 Deutschland Biocon Biologics Germany GmbH Tel: 0080008250910 Nederland Biocon Biologics France S.A.S Tel: 0080008250910 Eesti Biosimilar Collaborations Ireland Limited Tel: 0080008250910 Norge Biocon Biologics Finland OY Tlf: +47 800 62 671 Ελλάδα Biocon Biologics Greece ΜΟΝΟΠΡΟΣΩΠΗ Ι.Κ.Ε Τηλ.: 0080008250910 Österreich Biocon Biologics Germany GmbH Tel: 0080008250910 España Biocon Biologics Spain S.L.

Tel: 0080008250910 Polska Biosimilar Collaborations Ireland Limited Tel: 0 080008250910 France Biocon Biologics France S.A.S Tel: 0080008250910 Portugal Biocon Biologics Spain S.L.

Tel: 0080008250910 Hrvatska Biocon Biologics Germany GmbH Tel: 0080008250910 România Biosimilar Collaborations Ireland Limited Tel: 0080008250910 Ireland Biosimilar Collaborations Ireland Limited Tel: 1800 777 794 Slovenija Biosimilar Collaborations Ireland Limited Tel: 0080008250910 57 Ísland Biocon Biologics Finland OY Sími : +345 8004316 Slovenská republika Biocon Biologics Germany GmbH Tel: 0080008250910 Italia Biocon Biologics Spain S.L .

Tel: 0080008250910 Suomi/Finland Biocon Biologics Finland OY Puh/Tel: 99980008250910 Κύπρος Biosimilar Collaborations Ireland Limited Τηλ: 0080008250910 Sverige Biocon Biologics Finland OY Tel: 0080008250910 Latvija Biosimilar Collaborations Ireland Limited Tel: 0080008250910

This leaflet was last revised i n

Detailed information on this medicine is available on the European Medicines Agency web site: .. http://www.ema.europa. eu ————————————————————————————————————————— 58 The following information is intended for healthcare professio nals only In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Ogivri (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

Alwa ys keep this medicine in the closed original pack at a t emperat ure of 2 ºC – 8 ºC in a refrigerator.

A vial of Ogivri reconstituted with water for injections (not supplied) is stable for 10 days at 2 ºC – 8 ºC after reconstitution and must not be frozen.

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

Ogivri 150 mg powder for concentrate for solution for infusion Appropriate aseptic technique should be used. Each 150 mg vial of Ogivri is reconstituted with 7.2 mL of sterile 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 approxi mately 21 m g/mL trastuzumab. A volume overage of 4 % ensures that the labelled dose of 150 mg c an be withdrawn from each vial.

Ogivri 420 mg powder for concentrate for solution for infusion Appropriate aseptic technique should be used. Each 420 mg vial of Ogivri is reconstituted with 20 mL of sterile water for injection s (not supplied). Use of other reconstitution solvents should be avoided.

This yields a 21 mL solution for single -dose use, containing approximately 21 mg/mL trastuzumab. A volume overage of 4.8 % ensures that the labelled dose of 420 mg can be withdrawn from each vial.

Ogivri vial Volume of sterile water for injections Final concentration 150 mg vial + 7.2 mL = 21 mg/mL 420 mg vial + 20 mL = 21 mg/mL Instructions for r econstitution 1) Using a sterile syringe, slowly inject the appropriate volume (as noted above) of water for injections in the vial containing the lyophi lised Ogivri, 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 approxim ately 5 minutes. The reconstituted Ogivri results in a colourless to pale yellow transparent solution and should be essen tially free of visible particulates.

Determine the volume of the solution required:

• based on a loading dose of 4 mg trastu zumab/kg body weight, or a subsequent weekly dose of 2 mg trastuzum ab/kg body weight:

Volume (mL) = Body weight (kg) x dose (4 mg/kg for loadi ng or 2 mg/kg for maintenance) 21 (mg/m L, concentration of reconstitu ted solution)

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

Volume (mL) = Body weight (kg) x dose (8 mg/kg for loadi ng or 6 mg/kg for maintenance) 21 (mg/m L, concentration of reconstitu ted solution) The appropri ate amount of solution should be withd rawn from the vial using a sterile needle and syringe and added to a polyvin ylchloride, polyet hylene or polypro pylene infusion bag cont aining 250 mL of sodium chloride 9 mg/mL (0.9 %) solution for injection. Do not use with glucose- containing solutions. The bag should be gently inv erted to mix the solution in order to avoid foaming. Paren teral solutions should be inspected visually for particulates and discolorat ion prior to administration. Once the infusion is prepared it should be a dministered imm ediately. If diluted asepticall y, it may be stored for up to 90 days at 2 °C – 8 ° C and 24 hours at temperatures not exceeding 30 °C .

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Ogivri (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/18/1341).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.