Ogivri - patient leaflet, side effects, dosage

Patient leaflet - Ogivri

1. What Ogivri is and what it is used for

Ogivri 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 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.
You have metastatic breast cancer (breast cancer that has spread beyond the original tumour)

with high levels of HER2. Ogivri 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-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 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 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 may have to stop Ogivri treatment.

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 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 Ogivri.
you suffer from breathlessness, especially if you are currently using a taxane. Ogivri 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 Ogivri.

you have ever had any other treatment for cancer.

If you receive Ogivri 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

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

Other medicines and Ogivri

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

Pregnancy 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 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 baby 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 sodium.

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 receive 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 effects 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. How Ogivri 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 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 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.

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, metastatic breast cancer and metastatic gastric cancer, Ogivri is given every 3 weeks. Ogivri may also be given once a week for metastatic 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 (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

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 (depending 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 effects 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), 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.

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 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 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 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 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 Ogivri has finished, you should see your doctor and tell them that you have previously been treated with Ogivri.

Very common 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
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 (feeling sick)

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
inflammation of the breast
anxiety
inflammation of the liver
depression
kidney disorders
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 1000 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 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 lungs to develop in the womb
abnormal kidney development in the womb

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

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 the national reporting system listed inBy 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 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 injections, or

o 420 mg trastuzumab that has to be dissolved in 20 mL of water for injections.

– The resulting solution contains approximately 21 mg/mL trastuzumab.
– The other ingredient(s) 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).

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

Viatris Limited

Damastown Industrial Park

Mulhuddart

Dublin 15

DUBLIN

Ireland

Manufacturer

McDermott Laboratories Limited T/A Mylan Dublin Biologics

Newenham Court

Northern Cross

Malahide Road

Dublin 17

Ireland

Mylan Germany GmbH

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1

Bad Homburg v. d. Hoehe

Hessen, 61352,

Germany

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

België/Belgique/Belgien

Mylan EPD bvba/sprl

Tél/Tel: + 32 (0)2 658 61 00

Lietuva

Mylan Healthcare UAB

Tel: +370 5 205 1288

Efc^rapufl

Maw.iaH EOO4

Ten.: +359 2 44 55 400

Luxembourg/Luxemburg

Mylan EPD bvba/sprl

Tel: + 32 (0)2 658 61 00

(Belgique/Belgien)

Česká republika

Mylan Healthcare CZ s.r.o.

Tel: +420 222 004 400

Magyarorszag

Mylan EPD Kft

Tel: + 36 1 465 2100

Denmark

Viatris ApS

Tlf: +45 28 11 69 32

Malta

V.J. Salomone Pharma Ltd

Tel: + 356 21 22 01 74

Deutschland

Mylan Healthcare GmbH

Tel: +49 800 0700 800

Nederland

Mylan Healthcare B.V.

Tel: +31 (0)20 426 3300

Eesti

BGP Products Switzerland GmbH Eesti filiaal

Tel: + 372 6363 052

Norge

Viatris AS

Tel: + 47 66 75 33 00

EXÁáóa

BGP nPOÏONTA M.E.n.E.

TnX: +30 210 9891 777

Österreich

Mylan Österreich GmbH

Tel: +43 1 86390

España

Mylan Pharmaceuticals, S.L.

Tel: +34 900 102 712

Polska

Mylan Healthcare Sp. z o.o.

Tel: + 48 22 546 64 00

France

Mylan Medical SAS

Tel: +33 1 56 64 10 70

Portugal

Mylan, Lda.

Tel: + 351 21 412 72 56

Hrvatska

Mylan Hrvatska d.o.o.

Tel: +385 1 23 50 599

România

BGP Products SRL

Tel: + 40 372 579 000

Ireland

Mylan Ireland Limited

Tel: +353 1 8711600

Slovenija

Mylan Healthcare d.o.o.

Tel: + 386 1 236 31 80

Ísland

Icepharma hf

Símí: +354 540 8000

Slovenská republika

Mylan s.r.o.

Tel: +421 2 32 199 100

Italia

Mylan Italia SRL

Tel: + 39 02 612 46921

Suomi/Finland

Viatris OY

Puh/Tel: + 358 20 720 9555

Kúnpog

Varnavas Hadjipanayis Ltd.

Tql: + 357 2220 7723

Sverige

Mylan AB

Tel: + 46 855 522 750

Latvija

Mylan Healthcare SIA

Tel: +371 676 055 80

United Kingdom (Northern Ireland)

Mylan IRE Healthcare Limited

Tel: +353 18711600

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

The following information is intended for healthcare professionals only

Always keep this medicine in the closed original pack at a temperature of 2°C – 8 °C in a refrigerator. A vial of Ogivri reconstituted with water for injections (not supplied) is stable for 10 days at 2°C – 8°C 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 approximately 21 mg/mL trastuzumab. A volume overage of 4 % ensures that the labelled dose of 150 mg can 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 injections (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 reconstitution

1) Using a sterile syringe, slowly inject the appropriate volume (as noted above) of water for injections in the vial containing the lyophilised 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 approximately 5 minutes. The reconstituted Ogivri 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) 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 polyvinylchloride, polyethylene or polypropylene infusion bag containing 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 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 up to 90 days at 2°C – 8°C and 24 hours at temperatures not exceeding 30°C.