Phesgo

Package leaflet: Information for the user

Phesgo 600 mg/600 mg injection solution, 1200 mg/600 mg injection solution

pertuzumab/trastuzumab
Please read this leaflet carefully before you are given 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 Phesgo is and what it is used for
2. What you need to know before you are given Phesgo
3. How Phesgo is administered
4. Possible side effects
5. How to store Phesgo
6. Contents of the pack and other information

1. What Phesgo is and what it is used for

Phesgo is an anticancer medicine that contains two active substances: pertuzumab and trastuzumab.

• Pertuzumab and trastuzumab are “monoclonal antibodies” designed to recognise and bind to a specific target on cancer cells called “human epidermal growth factor receptor 2” (HER2).
• HER2 is present in large amounts on the surface of certain cancer cells and stimulates their growth.
• By binding to HER2 on cancer cells, pertuzumab and trastuzumab slow down or stop their growth or cause their death.

Phesgo is available in two different strengths. For further information, see section 6.
Phesgo is a medicine used to treat adult patients who have HER2-positive breast cancer; your doctor will test you to determine this characteristic. Phesgo may be used when:

• the cancer has spread to other parts of the body such as the lungs or liver (metastatic), or the cancer has returned in the breast and surrounding area but cannot be surgically removed, and no prior treatment with anticancer medicines (chemotherapy) or other medicines targeting HER2 has been given;
• the cancer has not spread to other parts of the body and treatment is given before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy).

During treatment with Phesgo, you will also be given other chemotherapy medicines. Information about these medicines is described in separate leaflets. Ask your doctor, pharmacist, or nurse to provide you with information on these other medicines.

2. What you should know before being given Phesgo

Phesgo must not be given to you

• if you are allergic to pertuzumab, trastuzumab, or any of the other ingredients of this medicine (listed in section 6).

If you have any doubts, consult your doctor, pharmacist, or nurse before being given Phesgo.
Warnings and precautions
Heart problems
Treatment with Phesgo may affect the heart. Before you are given Phesgo, speak to your doctor, pharmacist, or nurse:

• if you have had heart problems in the past (e.g. heart failure, treatment for severe irregular heartbeat, uncontrolled high blood pressure, recent heart attack). Your doctor will carry out certain tests to check that your heart is functioning properly before and during treatment with Phesgo;
• if you have previously had heart problems during prior treatment with a medicine containing trastuzumab;
• if you have previously been given a chemotherapeutic medicine belonging to the class of anticancer medicines known as anthracyclines, such as doxorubicin or epirubicin; these medicines can damage the heart muscle and increase the risk of heart problems with Phesgo;
• if you have previously undergone radiotherapy in the chest area, as this may increase the risk of heart problems.

If any of these conditions apply to you (or if you have any doubts), discuss them with your doctor or nurse before being given Phesgo. For further details on signs of heart problems to watch for, see section 4 “Serious unwanted effects”.
Injection reactions
Injection reactions, i.e. allergic reactions, may occur and can be severe.
If you experience any severe reaction, your doctor may stop treatment with Phesgo. See section 4 “Serious unwanted effects” for further information on injection reactions to monitor during and after the injection.
Your doctor or nurse will monitor you for unwanted effects during the injection and:

• for 30 minutes after the first injection of Phesgo;
• for 15 minutes after each subsequent injection of Phesgo. If you experience any severe reaction, your doctor may stop treatment with Phesgo.

Febrile neutropenia (low levels of white blood cells and fever)
Administration of Phesgo together with other chemotherapy treatments may cause a decrease in the number of white blood cells and lead to fever. If you have inflammation of the gastrointestinal tract (e.g. mouth inflammation or diarrhoea), you may be more likely to develop this unwanted effect. A persistent fever lasting several days may indicate worsening of your condition; in this case, you must contact your doctor.
Diarrhoea
Treatment with Phesgo may cause severe diarrhoea. Patients over 65 years of age have a higher risk of developing diarrhoea than patients under 65 years of age. If you experience severe diarrhoea while receiving anticancer treatment, your doctor may prescribe medications to control the diarrhoea and may also interrupt treatment with Phesgo until the diarrhoea is under control.
Children and adolescents
Phesgo must not be given to patients under 18 years of age, as there is no information available on its efficacy in this age group.
Elderly patients over 65 years of age
Patients over 65 years of age are more likely to experience unwanted effects such as decreased appetite, reduced number of red blood cells, weight loss, feeling of fatigue, loss or alteration of taste, sensation of weakness, numbness, tingling or prickling sensations, mainly in the feet and legs, and diarrhoea, compared to patients under 65 years of age.
Other medicines and Phesgo
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding, and contraception
Before starting treatment, you must inform your doctor, pharmacist, or nurse if you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding with breast milk. Your doctor, pharmacist, or nurse will discuss with you the benefits and risks to you and your baby associated with treatment with Phesgo during pregnancy.

• Inform your doctor immediately if you become pregnant during treatment with Phesgo or within 7 months after stopping treatment. Phesgo may cause harm to the unborn baby. You must use effective contraceptive methods during treatment with Phesgo and for 7 months after stopping treatment.
• Ask your doctor whether you can breastfeed during or after treatment with Phesgo.

Driving and using machines
Phesgo may affect your ability to drive vehicles or operate machinery. If during treatment you develop symptoms such as dizziness, chills, fever, injection reactions, or any type of allergic reaction, as described in section 4, you must not drive or use machinery until these symptoms have resolved.
Phesgo contains sodium
Phesgo contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.
Phesgo contains polysorbate 20 (E 432)
This medicine contains 6.0 mg of polysorbate 20 per 15 mL vial and 4.0 mg of polysorbate 20 per 10 mL vial. Polysorbates may cause allergic reactions.
Inform your doctor if you have known allergies.

3. How Phesgo is administered

Phesgo will be administered to you by a doctor or nurse as an injection under the skin (subcutaneous injection). Treatment will begin in a hospital or clinic. If you tolerate the treatment well, your doctor may decide whether you can receive Phesgo outside the hospital or clinic, for example at home.

• The injections will be given every three weeks.
• The injection will first be administered in one thigh, then in the other. Injections will continue to alternate between these two sites.
• The doctor or nurse will ensure that each injection is given at a new site (at least 2.5 cm away from a previous injection site) and in areas where the skin is not red, bruised, tender, or hardened.
• Different injection sites must be used when administering other medicines.

Starting treatment (loading dose)

• Phesgo 1200 mg/600 mg will be administered as a subcutaneous injection over 8 minutes. The doctor or nurse will monitor you for any adverse reactions during the injection and for 30 minutes afterwards.
• You will also be given chemotherapy medicines.

Subsequent injections (maintenance doses), if the first injection did not cause serious adverse reactions:

• Phesgo 600 mg/600 mg will be administered as a subcutaneous injection over 5 minutes. The doctor or nurse will monitor you for any adverse reactions during the injection and for 15 minutes afterwards.
• You will also be given chemotherapy medicines, as prescribed by your doctor.
• The number of injections you will receive depends on:
  • your response to treatment;
  • whether treatment is given before or after surgery, or due to disease progression.

For further information on loading and maintenance doses, see section 6.
For further information on chemotherapy administration (which may also cause adverse reactions), please read the package leaflet of those medicines. If you have any doubts about these medicines, consult your doctor, pharmacist, or nurse.
Administration outside the clinical setting
Information for healthcare professionals on how to prepare and administer Phesgo is provided at the end of this leaflet.
If you forget to take Phesgo
If you miss an appointment for Phesgo administration, schedule another appointment as soon as possible. Depending on the time elapsed between appointments, your doctor will decide the appropriate dose of Phesgo to administer.
If you stop treatment with Phesgo
Do not stop treatment with this medicine without first talking to your doctor. It is important that the full course of injections is administered at the correct time every three weeks. This will allow the medicine to work optimally.
If you have any questions about the use of 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.
Serious side effects
If you notice any of the following side effects, tell your doctor or nurse immediately.

• Heart problems: slowed or rapid heartbeat compared to normal, or heart fluctuations, and symptoms which may include cough, shortness of breath, and oedema (fluid retention) in the legs or arms.
• Reactions to the injection: with symptoms that may be mild or more severe, and which may include feeling unwell, fever, chills, feeling tired, headache, loss of appetite, joint and muscle pain, hot flushes.
• Diarrhoea: with symptoms that may be mild or moderate, but also very severe or persistent, with 7 or more watery bowel movements per day.
• Decrease in the number of white blood cells, shown in a blood test, which may or may not be associated with fever.
• Allergic reactions: with symptoms that may include swelling of the face and throat with difficulty breathing, which may be a sign of a severe allergic reaction.

If you notice any of the above side effects, tell your doctor or nurse immediately.
Other side effects
Very common (may affect more than 1 in 10 people):

• hair loss
• rash
• inflammation of the digestive tract (e.g. sore mouth)
• decrease in the number of red and white blood cells, detectable with a blood test
• muscle weakness
• constipation
• loss or change in taste
• difficulty sleeping
• sensation of weakness, numbness, tingling, or prickling, mainly in the feet, legs, and hands
• nosebleeds
• heartburn
• dry skin, itching, or acne-like rash
• pain, redness of the skin (erythema), and bruising at the injection site
• nail problems, such as discolouration, for example white or dark stripes, or change in nail colour
• sore throat, redness of the nose, nasal pain or excessive nasal discharge, flu-like symptoms and fever which may lead to ear, nose, or throat infection
• increased tear production
• body aches, in arms, legs, and abdomen
• sharp, shooting, or pulsating pain, or associated with sensation of cold/heat
• pain sensation caused by something that should not be painful, such as a light touch
• loss of balance or coordination.

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

• difficulty breathing
• reduced ability to perceive temperature changes
• inflammation of the nail bed at the point where the nail and skin meet
• condition associated with impaired function of the left side of the heart, with or without symptoms
• condition associated with weakening of the heart muscle, which may lead to difficulty breathing
• allergic reaction, which may cause a range of symptoms, mild or severe, such as fever, chills, headache, and difficulty breathing.

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

• chest symptoms, such as dry cough or breathlessness (possible signs of “interstitial lung disease”, a condition involving damage to the tissues around the lung alveoli)
• fluid around the lungs, causing difficulty breathing.

Rare side effects such as tumour lysis syndrome (a condition caused by the rapid death of tumour cells) have been observed with intravenous pertuzumab, but not with Phesgo. Symptoms of tumour lysis syndrome may include: kidney problems (signs of which include weakness, shortness of breath, fatigue, and confusion), heart problems (signs of which include heart fluctuations or increased or decreased heartbeat), seizures, vomiting or diarrhoea, and tingling of the mouth, hands, or feet.
If you experience any of the above side effects, contact your doctor, nurse, or pharmacist.
If you experience any of the above symptoms after stopping treatment with Phesgo, contact your doctor immediately and inform them that you were previously treated with Phesgo.
Some of the side effects experienced may be due to the breast cancer itself. If Phesgo is administered together with chemotherapy, some side effects may also be due to these other medicines.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through 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 Phesgo

Phesgo will be stored by healthcare professionals at the hospital or clinic. The storage instructions are as follows:

• 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 vial after “Exp./EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2°C–8°C).
• Do not freeze.
• Keep the vial in the outer packaging to protect the medicine from light.
• After opening the vial, the solution should be used immediately. Do not use this medicine if you notice the presence of particles in the liquid or if the colour has changed (see section 6).
• 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 Phesgo contains
The active substances are pertuzumab and trastuzumab.

• a 10 mL vial of solution contains 600 mg of pertuzumab and 600 mg of trastuzumab. Each mL contains 60 mg of pertuzumab and 60 mg of trastuzumab.
• a 15 mL vial of solution contains 1200 mg of pertuzumab and 600 mg of trastuzumab. Each mL contains 80 mg of pertuzumab and 40 mg of trastuzumab.

The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine
monohydrochloride monohydrate, α,α-trehalose dihydrate, sucrose, L-methionine, polysorbate 20 and water for
injection (see section 2 “Phesgo contains sodium”, “Phesgo contains polysorbates”).

Description of the appearance of Phesgo and contents of the pack
Phesgo is an injectable solution. It is a liquid ranging from clear to opalescent, colourless to brownish,
supplied in a glass vial. Each pack contains one 10 mL or one 15 mL vial of solution.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg UAB “Roche Lietuva”
N.V. Roche S.A. Tel: +370 5 2546799
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11

България
Рош България ЕООД
Тел: +359 2 474 5444

Česká republika Magyarország
Roche s.r.o. Roche (Magyarország) Kft.
Tel: +420 − 2 20382111 Tel: +36 - 1 279 4500

Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99

Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050

Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 - 6 177 380 Tlf: +47 - 22 78 90 00

Ελλάδα, Kύπρος Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Ελλάδα Tel: +43 (0) 1 27739
Τηλ: +30 210 61 66 100

España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88

France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0) 1 47 61 40 00 Tel: +351 - 21 425 70 00

Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: +385 1 4722 333 Tel: +40 21 206 47 01

Ireland, Malta Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Ireland/L-Irlanda Tel: +386 - 1 360 26 00
Tel: +353 (0) 1 469 0700

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Sverige
Roche AB
Tel: +46 (0) 8 726 1200

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

Administration of Phesgo 600/600 mg solution for injection outside the clinical setting.
Any healthcare professional administering treatment outside the clinical setting must be fully informed about both the administration method and the potential risks associated with Phesgo.
The healthcare professional must ensure that appropriate medications for managing hypersensitivity reactions are readily available, in accordance with local standard clinical practice (depending on the severity and type of reaction, e.g., epinephrine, beta-agonists, antihistamines, and corticosteroids) for immediate use.
Phesgo must be stored at 2 °C–8 °C in its original packaging until the time of use.

Instructions for use
Phesgo must be administered only by subcutaneous injection. Phesgo is not intended for intravenous administration.
To prevent administration errors, it is important to check the vial label to ensure that the prepared and administered medicine is Phesgo 600/600 mg (15 mL vial containing 10 mL of solution).
Phesgo should be inspected visually for particles or discoloration prior to administration. If particles or discoloration are observed, the vial must be discarded according to local waste disposal guidelines. Do not shake the vial.
Before use, allow the Phesgo vial to reach room temperature for approximately 15 minutes prior to preparing an injection.
A syringe, transfer needle, and injection needle are required to withdraw the Phesgo solution from the vial and administer it subcutaneously. Phesgo may be injected using hypodermic needles ranging from 25G–27G in gauge and 3/8" (10 mm) to 5/8" (16 mm) in length. Phesgo is compatible with stainless steel, polypropylene, polycarbonate, polyethylene, polyurethane, polyvinyl chloride, and fluorinated ethylene propylene.
Since Phesgo does not contain any antimicrobial preservative, the medicinal product must be used immediately. The hypodermic injection needle should be attached to the syringe immediately before administration, followed by adjustment of the volume to 10 mL.
The injection site should be alternated only between the left and right thigh. New injections should be administered at least 2.5 cm away from the previous injection site into healthy skin, and never into areas where the skin is red, bruised, tender, or hard. The dose must not be divided between two syringes or across two administration sites.
The dose should be administered over a 5-minute period. The injection may be slowed or paused if the patient experiences injection-related symptoms.
A 15-minute observation period is recommended after completion of the injection, during which patients should be monitored for injection-related reactions and hypersensitivity reactions.
Patients should be instructed on how to recognize symptoms of hypersensitivity reactions or other potentially serious adverse effects (as described in Section 4 of the patient leaflet) and advised to contact a healthcare professional if symptoms occur after the healthcare provider has left the patient.
Phesgo is for single use only. Any unused medicine or waste material must be disposed of in accordance with local regulations. The name and batch number of the administered product must be clearly recorded.