OGIVRI 420 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Ogivri 150 mg powder for concentrate for solution for infusion

Ogivri 420 mg powder for concentrate for solution for infusion

trastuzumab

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 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.

Contents of the pack

1. What is Ogivri and what is it used for
2. What you need to know before you use Ogivri
3. How to use Ogivri
4. Possible side effects
5. Storage of Ogivri
6. Contents of the pack and other information

1. What is Ogivri and what is it used for

Ogivri contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies recognize specific proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large quantities on the surface of some cancer cells and stimulates the growth of these cells. When Ogivri binds to HER2, it slows down the growth of these cells, causing them to die.

Your doctor may prescribe Ogivri for the treatment of breast or 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 from the original tumor) with high levels of HER2. Ogivri may be prescribed in combination with chemotherapy medications paclitaxel or docetaxel as first-line treatment for metastatic breast cancer or may be prescribed alone if other treatments have not been successful. It is also used in combination with other medications called aromatase inhibitors in patients with high levels of HER2 and positive hormone receptor for metastatic breast cancer (cancer that is sensitive to female sex hormones).
• You have metastatic gastric cancer with high levels of HER2, and it is combined with other cancer medications such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before you use Ogivri

Do not use Ogivri:

• If you are allergic to trastuzumab, mouse proteins, or any of the other components of this medication (listed in section 6).
• If you have severe respiratory problems at rest due to your tumor or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac reviews

Treatment with Ogivri alone or in combination with a taxane may affect the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two types of medications used to treat cancer).

The effects can be moderate to severe and can be fatal. Therefore, you will need to have your heart function checked before, during (every three months), and after (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 will be checked more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to stop treatment with Ogivri.

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

• You have had heart failure, coronary artery disease, heart valve disease (heart murmur), or high blood pressure, have taken any medication for high blood pressure, or are currently taking any medication for high blood pressure.
• You have previously received or are currently receiving a medication called doxorubicin or epirubicin (medications for treating cancer). These medications (or any other anthracycline) can damage the heart muscle and increase the risk of heart problems when treated with Ogivri.
• You feel short of breath, especially if you are currently receiving a taxane. Ogivri can cause difficulty breathing, especially when administered for the first time. This could be more severe if you already have shortness of breath. In very rare cases, patients with severe breathing difficulties before treatment have died when given Ogivri.
• You have had any other cancer treatment.

If you receive Ogivri with any other medication for treating cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflets of these medications.

Children and adolescents

Ogivri is not recommended for children under 18 years of age.

Other medications and Ogivri

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medications.

It may take 7 months for Ogivri to be completely eliminated from the body. Therefore, if you are going to take any new medication within 7 months after finishing treatment, you should tell your doctor, pharmacist, or nurse that you have been treated with Ogivri.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before using this medication.

Pregnancy

• You must use an effective contraceptive method during treatment with Ogivri and for at least 7 months after finishing treatment.
• Your doctor will explain the risks and benefits of taking Ogivri during pregnancy. In rare cases, a decrease in the fluid surrounding the developing baby in the uterus (amniotic fluid) has been observed in pregnant women who were given trastuzumab. This can be harmful to the baby in the uterus and has been associated with underdeveloped lungs, resulting in fetal death.

Breastfeeding

You should not breastfeed your baby during therapy with Ogivri and up to 7 months after the last dose of Ogivri, as this medication may pass into your breast milk. Consult your doctor or pharmacist before taking any medication.

Driving and using machines

Ogivri may affect your ability to drive a vehicle or operate machinery. If you experience symptoms during treatment, such as dizziness, drowsiness, chills, or fever, do not drive or use machinery until these symptoms have resolved.

Ogivri contains sorbitol (E-420) and sodium

Ogivri 150 mg powder for concentrate for solution for infusion

This medication contains 115.2 mg of sorbitol in each vial.

Ogivri 420 mg powder for concentrate for solution for infusion

This medication contains 322.6 mg of sorbitol in each vial.

Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, you should not receive this medication. Patients with HFI cannot break down fructose, which can cause serious side effects. Consult your doctor before receiving this medication if you have HFI or cannot consume sweet foods or drinks because they cause unpleasant effects such as bloating, stomach cramps, or diarrhea.

Ogivri contains less than 23 mg of sodium (1 mmol) per vial; this is essentially "sodium-free".

3. How to use Ogivri

Before starting treatment with Ogivri, your doctor will determine the amount of HER2 in your tumor. Only patients with high levels of HER2 will be treated with Ogivri. Ogivri should only be administered by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is suitable for you. The dose of Ogivri depends on your body weight.

The first dose of your treatment is administered over approximately 90 minutes, and you will be observed by a healthcare professional while it is being administered, in case any adverse reaction occurs. If the initial dose has been well tolerated, subsequent doses may be administered over 30 minutes (see section 2 "Warnings and precautions"). The number of infusions you can receive will depend on your response to treatment. Your doctor will inform you about this.

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

For early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Ogivri will be administered every 3 weeks. Ogivri may also be administered once a week for metastatic breast cancer.

To avoid medication errors, it is essential to check the labels of the vials to ensure that the medication being prepared and administered is Ogivri (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

If you interrupt treatment with Ogivri

Do not stop treatment with this medication without first talking to your doctor. All doses should be taken at the right time, every week or every three weeks (depending on your dosing schedule). This helps your medication work properly.

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

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everybody gets them.

Some of these side effects can be serious and may require hospitalization.

During the administration of an Ogivri infusion, chills, fever, and other flu-like symptoms may occur. This is very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: feeling unwell (nausea), vomiting, pain, increased muscle tension, and agitation, headache, dizziness, difficulty breathing, decreased or increased blood pressure, changes in heart rhythm (palpitations, arrhythmias, or irregular heartbeat), swelling of the face and lips, rash, and feeling tired. Some of these symptoms can be severe, and some patients have died (see section 2 "Warnings and precautions").

These effects usually occur during the first intravenous infusion and during the first few hours after the start of the infusion. They are usually temporary. A healthcare professional will monitor you 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 have any reaction, the infusion may be administered more slowly or stopped, and you may be given treatment to counteract the side effects. The infusion can continue once your symptoms have improved.

Occasionally, symptoms may start after 6 hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms can improve and then worsen later.

Serious side effects

Other side effects may occur at any time during treatment with Ogivri and not only those related to the infusion.

Tell your doctor or nurse if you experience any of the following side effects:

• Heart problems can occur during treatment and, occasionally, after stopping treatment, and these can be serious. These include weakening of the heart muscle, which can cause heart failure, inflammation of the layer surrounding the heart, and changes in heart rhythm. This can cause symptoms such as shortness of breath (even if it is shortness of breath at night), cough, fluid retention (swelling) in the legs or arms, palpitations (arrhythmias or irregular heartbeat) (see section 2 "Cardiac reviews"). Your doctor will monitor your heart regularly during and after treatment, but you should tell your doctor immediately if you notice any of the symptoms described above.

• Tumor lysis syndrome (a set of metabolic complications that occur after cancer treatment, characterized 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 (heart palpitations or a faster or slower heartbeat), seizures, vomiting, or diarrhea, and tingling in the mouth, hands, or feet.

If you experience any of these symptoms when your treatment with Ogivri has finished, you should consult your doctor and inform them that you have been previously treated with Ogivri.

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• weakness
• skin rash
• chest pain
• abdominal pain (stomach)
• joint pain
• low count of red and white blood cells, which help fight infection, sometimes with fever
• muscle pain
• conjunctivitis (itchy, watery eyes and eyelids, with a crusty appearance)
• tearing
• nasal bleeding
• nasal discharge
• hair loss
• tremors
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling in the fingers and toes, which can occasionally spread to the rest of the limb
• redness, swelling, or ulcers in the mouth and/or throat
• pain, swelling, redness, or tingling in the hands and/or feet
• difficulty breathing
• headache
• cough
• vomiting
• nausea (feeling unwell)

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

• allergic reactions
• dry mouth and skin
• throat infections
• dry eyes
• bladder and skin infections
• sweating
• feeling weak and unwell
• breast inflammation
• anxiety
• liver inflammation
• depression
• kidney problems
• increased muscle tone (hypertonia)
• asthma
• lung infections
• pain in the arms and/or legs
• lung problems
• skin rash with itching
• back pain
• feeling sleepy (somnolence)
• neck pain
• hemorrhoids (inflammation of the blood vessels surrounding the anus)
• bone pain
• itching
• acne
• leg cramps

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

• hearing loss
• skin rash with blisters
• wheezing (whistling)
• inflammation/scarring of the lungs

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

• jaundice (yellow color in the skin and the white part of the eyes)
• anaphylactic reactions (sudden severe allergic reaction with symptoms such as rash, itching, difficulty breathing, or feeling dizzy or faint)

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

• abnormal blood clotting or coagulation disorders
• high levels of potassium
• inflammation or bleeding in the back of the eyes
• shock (a dangerous drop in blood pressure, which can cause symptoms such as rapid and shallow breathing, coolness, sweaty skin, a fast and weak pulse, dizziness, weakness, and fainting)
• inflammation of the heart lining
• difficulty breathing
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low oxygen levels in the blood
• difficulty breathing while lying down
• liver damage
• inflammation of the face, lips, and throat
• kidney failure
• abnormally low levels of fluid surrounding the fetus in the uterus
• failure of the fetus's lungs to develop in the uterus
• abnormal development of the fetus's kidneys in the uterus

Some of the side effects you may experience may be due to your breast cancer. If you are given Ogivri in combination with chemotherapy, some of the effects may also be due to the chemotherapy itself.

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of 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 carton and on the label of the vial after CAD or EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (between 2 °C and 8 °C).

The infusion solutions should be used immediately after dilution. Do not use Ogivri if you notice any foreign particles or discoloration before administration.

Medicines should not be disposed of 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 Additional Information

Composition of Ogivri

• The active substance is trastuzumab. Each vial contains:
  • 150 mg of trastuzumab which is dissolved in 7.2 ml of water for injections or
  • 420 mg of trastuzumab which is dissolved in 20 ml of water for injections.

• The resulting solution contains approximately 21 mg/ml of trastuzumab.
• The other ingredients are L-histidine hydrochloride, L-histidine, sorbitol (E-420)

(see section 2 “Ogivri contains sorbitol (E-420) and sodium”), macrogol 3350, hydrochloric acid, and sodium hydroxide (for pH adjustment).

Appearance and Package Contents

Ogivri is a powder for concentrate for solution for intravenous infusion, presented in a glass vial with a rubber stopper containing 150 mg or 420 mg of trastuzumab. It is a white to pale yellow lyophilized 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

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Date of last revision of this leaflet: 11/2024

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended only for healthcare professionals

To avoid medication errors, it is essential to check the labels on the vials to ensure that the medicine being prepared and administered is Ogivri (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicine in its original closed container at a temperature between 2 °C - 8 °C in the refrigerator. The reconstituted Ogivri vial with water for injections (not provided in the pack) is stable for 10 days at a temperature between 2 °C - 8 °C after reconstitution and should not be frozen.

Ogivri should be handled carefully during reconstitution. If excessive foam is formed during reconstitution or the reconstituted Ogivri is shaken, it may cause problems with the amount of Ogivri that can be withdrawn from the vial.

Ogivri 150 mg powder for concentrate for solution for infusion

A suitable aseptic technique should be used. Each 150 mg vial of Ogivri is reconstituted with 7.2 ml of sterile water for injections (not provided). The use of other solvents for reconstitution should be avoided. This yields a 7.4 ml single-dose solution containing approximately 21 mg/ml of trastuzumab. A 4% overfill allows the labeled dose of 150 mg to be withdrawn from each vial.

Ogivri 420 mg powder for concentrate for solution for infusion

A suitable aseptic technique should be used. Each 420 mg vial of Ogivri is reconstituted with 20 ml of sterile water for injections (not provided in the pack). The use of other solvents for reconstitution should be avoided. This yields a 21 ml single-dose solution containing approximately 21 mg/ml of trastuzumab. A 4.8% overfill allows the labeled dose of 420 mg to be withdrawn from each vial.

Reconstitution Instructions

1. Using a sterile syringe, slowly inject the appropriate volume (as indicated above) of water for injections into the vial containing the Ogivri lyophilized powder, directing the stream towards the lyophilized powder.
2. Gently swirl the vial in a circular motion to aid reconstitution. DO NOT SHAKE!

Formation of a slight foam after reconstitution is common. Allow the vial to stand for approximately 5 minutes. Reconstituted Ogivri is a clear to pale yellow solution and should be essentially free of visible particles.

The required volume of solution will be determined:

• Based on the initial dose of 4 mg of trastuzumab/kg body weight or subsequent weekly doses of 2 mg of trastuzumab/kg body weight:

• The required volume of solution will be determined based on the initial dose of 8 mg of trastuzumab/kg body weight or doses every 3 weeks of 6 mg of trastuzumab/kg body weight:

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to a polyvinyl chloride, polyethylene, or polypropylene infusion bag containing 250 ml of sodium chloride 9 mg/ml (0.9%) injection. Do not use with solutions containing glucose. The bag should be gently inverted to mix the solution and avoid foam formation. Parenteral solutions should be inspected visually for particles and discoloration before administration. Once the infusion is prepared, it should be administered immediately. If aseptically diluted, it can be stored for up to 90 days at 2°C - 8°C and 24 hours at temperatures not exceeding 30 °C.