KADCYLA 160 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Kadcyla 100mg powder for concentrate for solution for infusion

Kadcyla 160mg powder for concentrate for solution for infusion

trastuzumab emtansine

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 experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Kadcyla and what is it used for

What is Kadcyla

Kadcyla contains the active substance trastuzumab emtansine, which is made up of two parts that are linked together:

• trastuzumab – a monoclonal antibody that selectively binds to an antigen (a protein that the medicine acts on) called human epidermal growth factor receptor 2 (HER2). HER2 is found in large quantities on the surface of some cancer cells, stimulating their growth. When trastuzumab binds to HER2, it can stop the growth of cancer cells and cause them to die.
• DM1 – an anticancer substance that is activated once Kadcyla enters the cancer cell.

What Kadcyla is used for

Kadcyla is used to treat adult patients with breast cancer when:

• the cancer cells contain a large amount of the HER2 protein – your doctor will test your cancer cells to find out.
• you have already been treated with the medicine trastuzumab and a medicine from a group called taxanes.

• the cancer has spread to areas near the breast or to other parts of the body (metastasized).
• the cancer has not spread to other parts of the body and the treatment is given after surgery (treatment after surgery is called adjuvant therapy).

2. What you need to know before you are given Kadcyla

You must not be given Kadcyla

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

If you meet the above condition, you must not be given Kadcyla. If you are not sure, talk to your doctor or nurse before you are given Kadcyla.

Warnings and precautions

Talk to your doctor or nurse before you are given Kadcyla if:

• you have ever had a severe infusion-related reaction during treatment with trastuzumab, characterized by symptoms such as flushing, chills, fever, shortness of breath, difficulty breathing, rapid heartbeat, or low blood pressure.
• you are receiving treatment with medicines that thin the blood (such as warfarin, heparin).
• you have any history of liver problems. Your doctor will perform blood tests to check your liver function before starting treatment and regularly during treatment.

If any of the above conditions apply to you (or you are not sure), talk to your doctor or pharmacist before you are given Kadcyla.

Monitoring for side effects

Kadcyla may worsen some existing conditions or cause side effects. See section 4 for more information on side effects to watch out for.

Tell your doctor or nurse immediately if you notice any of the following serious side effects while you are receiving Kadcyla:

• Respiratory problems:Kadcyla may cause serious respiratory problems, such as shortness of breath (at rest or during any activity) and cough. These signs may indicate inflammation of the lung, which could be serious and even life-threatening. If you develop lung disease, your doctor may stop treatment with this medicine.

• Liver problems:Kadcyla may cause inflammation or damage to liver cells, which can cause your liver to stop working normally. When liver cells are inflamed or damaged, they can release substances into the blood that are higher than normal, which can make liver enzymes elevated in blood tests. In most cases, you will not have any symptoms. One symptom could be yellowing of the skin and eyes (jaundice). Your doctor will perform blood tests to check your liver function before starting treatment and regularly during treatment.

A rare anomaly that can affect the liver is a condition known as nodular regenerative hyperplasia (NRH). This anomaly causes changes in the structure of the liver and can affect liver function. Patients who develop this anomaly develop multiple nodules in the liver that can affect liver function. Over time, symptoms such as feeling full or bloated in the abdomen due to fluid accumulation or bleeding from the formation of abnormal blood vessels in the esophagus or rectum may appear.

• Heart problems:Kadcyla may weaken the heart muscle. When the heart muscle is weakened, symptoms such as shortness of breath at rest or when sleeping, chest pain, swelling of legs or arms, or feeling of rapid or irregular heartbeat may appear. Your doctor will check your heart function before starting treatment and regularly during treatment. If you notice any of the symptoms described above, tell your doctor immediately.

• Infusion-related reactions or allergic reactions: Kadcyla may cause flushing, chills, fever, difficulty breathing, low blood pressure, rapid heartbeat, swelling of the face or tongue, or problems swallowing during or after infusion on the first day of treatment. Your doctor or nurse will check if you are experiencing any of these side effects. If you develop a reaction, the infusion rate may be slowed down or stopped, and you may be given treatment to counteract the side effects. The infusion may continue after the symptoms improve.

• Bleeding:Kadcyla may cause a decrease in the number of platelets in the blood. Platelets help the blood to clot, so you may experience bruising or spontaneous bleeding (such as nosebleeds or bleeding gums). Your doctor will perform blood tests regularly to check if your platelet count is low. If you notice any bruising or spontaneous bleeding, tell your doctor immediately.

• Nerve problems:Kadcyla may cause nerve damage. Symptoms you may experience include tingling, pain, numbness, itching, prickling, or burning sensations in your hands and feet. Your doctor will monitor you for signs and symptoms of nerve problems.

• Reaction at the injection site:If you experience a burning sensation, pain, or sensitivity at the injection site during infusion, this could indicate that Kadcyla has leaked out of the blood vessel. Tell your doctor or nurse immediately. If Kadcyla leaks out of the blood vessel, it may cause increased pain, discoloration, blistering, and peeling of the skin (necrosis) at the injection site in the days or weeks following infusion.

Tell your doctor or nurse immediately if you experience any of the side effects mentioned above.

Children and adolescents

Kadcyla is not recommended for patients under 18 years of age because there is no information on its efficacy in this age group.

Other medicines and Kadcyla

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

In particular, talk to your doctor or pharmacist if you are taking:

• medicines that thin the blood, such as warfarin, or reduce the ability to form blood clots, such as aspirin
• medicines for treating fungal infections, such as ketoconazole, itraconazole, or voriconazole
• antibiotics for infections, such as clarithromycin or telithromycin
• medicines for treating HIV, such as atazanavir, indinavir, nelfinavir, ritonavir, or saquinavir
• a medicine for depression called nefazodone

If any of the above conditions apply to you (or you are not sure), talk to your doctor or pharmacist before you are given Kadcyla.

Pregnancy

Kadcyla is not recommended if you are pregnant, as this medicine may harm the fetus.

• Before starting treatment with Kadcyla, tell your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.
• You must use an effective method of contraception to prevent pregnancy during treatment with Kadcyla. Talk to your doctor about the best contraceptive method for you.
• You must continue to use an effective method of contraception for at least 7 months after your last dose of Kadcyla. Talk to your doctor before stopping your contraceptive method.
• Male patients or their female partners must also use an effective method of contraception.
• Tell your doctor immediately if you become pregnant during treatment with Kadcyla.

Breast-feeding

You must not breast-feed during treatment with Kadcyla and for 7 months after your last infusion of Kadcyla. It is not known whether the components of Kadcyla pass into breast milk. Talk to your doctor.

Driving and using machines

Kadcyla is not expected to affect your ability to drive or use tools or machines. If you experience flushing, chills, fever, difficulty breathing, low blood pressure, or rapid heartbeat (infusion-related reactions), blurred vision, tiredness, headache, or dizziness, do not drive, cycle, or use tools or machines until these symptoms have resolved.

Important information about some of the ingredients of Kadcyla

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

3. How Kadcyla is given

Kadcyla will be given to you by a doctor or nurse in a hospital or clinic.

• It is given by infusion into a vein (intravenous infusion).
• You will receive an infusion every 3 weeks.

How much medicine will you be given

• You will be given 3.6 mg of Kadcyla per kilogram of body weight. Your doctor will calculate the correct dose for you.
• The first infusion will be given over 90 minutes. Your doctor or nurse will monitor you during the infusion and for at least 90 minutes after it is finished, to check for side effects.
• If the first infusion is well tolerated, the next infusion can be given over 30 minutes. You will be monitored by a doctor or nurse during the infusion and for at least 30 minutes after it is finished, to check for side effects.
• The number of infusions you receive will depend on how you respond to treatment and what you are being treated for.
• If you experience side effects, your doctor may decide to continue treatment, although they may use a lower dose or delay or stop treatment.

If you miss a dose of Kadcyla

If you miss or do not attend your appointment to receive Kadcyla, make another appointment as soon as possible. Do not wait until your next scheduled appointment.

If you stop treatment with Kadcyla

Do not stop using this medicine without talking to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if you notice any of the following serious side effects:

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

• Kadcyla may cause inflammation or damage to liver cells, which can cause liver enzymes to be elevated in blood tests. However, in most cases observed during treatment with Kadcyla, these elevations are mild and temporary, do not cause symptoms, and do not affect liver function.
• Bruising and spontaneous bleeding (such as nosebleeds).
• Tingling, pain, numbness, itching, prickling, or burning sensations in the hands and feet. These symptoms may indicate nerve damage.

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

• Flushing, chills, fever, difficulty breathing, low blood pressure, or rapid heartbeat during or up to 24 hours after infusion. These are reactions known as infusion-related reactions.
• Heart problems may occur. Most patients will not have symptoms of heart problems. If symptoms occur, they may include cough, shortness of breath at rest or when sleeping, chest pain, swelling of ankles or arms, or feeling of rapid or irregular heartbeat.

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

• Inflammation of the lungs that can cause breathing problems, such as shortness of breath (at rest or during any activity), cough, or dry coughing spells, which are signs of lung tissue inflammation.
• Yellowing of the skin and eyes (jaundice), which could be a sign of severe liver damage.
• Allergic reactions may occur, and most patients will have mild symptoms such as itching or tightness in the chest. In more severe cases, swelling of the face or tongue, problems swallowing, or difficulty breathing may occur.

Frequency not known:

• If the Kadcyla infusion solution leaks into the tissues around the injection site, it may cause pain, discoloration, blistering, and peeling of the skin (necrosis) at the injection site. Contact your doctor or nurse immediately.

Tell your doctor or nurse immediately if you notice any of the serious side effects listed above.

Other side effects

Very common:

• decrease in the number of red blood cells (shown in a blood test)
• nausea (vomiting)
• diarrhea
• dry mouth
• urinary tract infection
• constipation
• stomach pain
• cough
• difficulty breathing
• mouth inflammation
• difficulty sleeping
• muscle or joint pain
• fever
• headache
• fatigue
• weakness

Common:

• chills or flu-like symptoms
• decrease in potassium levels (shown in a blood test)
• rash
• decrease in the number of white blood cells (shown in a blood test)
• dry eyes, watery eyes, or blurred vision
• red eyes or eye infection
• indigestion
• swelling of the legs and/or arms
• gum bleeding
• high blood pressure
• feeling dizzy
• taste disturbances
• itching
• difficulty remembering
• hair loss
• skin reaction on the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia syndrome)
• nail disorders

Uncommon:

• A rare anomaly that can be caused by Kadcyla is a condition known as nodular regenerative hyperplasia of the liver. This anomaly causes changes in the structure of the liver and can affect liver function. Patients who develop this anomaly develop multiple nodules in the liver that can affect liver function. Over time, symptoms such as feeling full or bloated in the abdomen due to fluid accumulation or bleeding from the formation of abnormal blood vessels in the esophagus or rectum may appear.
• During infusion of Kadcyla, the infused liquid may leak into the surrounding tissues and cause pain, skin irritation, or inflammation at the infusion site.

If you experience any of the side effects listed above after treatment with Kadcyla has been stopped, you should talk to your doctor or nurse and inform them that you have been treated with Kadcyla.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Kadcyla

Kadcyla will be stored by healthcare professionals in the hospital or clinic.

• 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. The expiry date is the last day of the month shown.
• Store in a refrigerator (2°C - 8°C). Do not freeze.
• Once the infusion solution is prepared, Kadcyla is stable for a maximum of 24 hours at a temperature between 2°C and 8°C and must be discarded after this time.
• 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. Container Contents and Additional Information

Kadcyla Composition

• The active ingredient is trastuzumab emtansine.
• Kadcyla 100mg: A vial of powder for concentrate for solution for infusion contains 100 mg of trastuzumab emtansine. After reconstitution, a 5 ml vial of solution contains 20 mg/ml of trastuzumab emtansine.
• Kadcyla 160 mg: A vial of powder for concentrate for solution for infusion contains 160 mg of trastuzumab emtansine. After reconstitution, an 8 ml vial of solution contains 20 mg/ml of trastuzumab emtansine.
• The other components are succinic acid, sodium hydroxide (see section 2 "Important information about some of the components of Kadcyla"), sucrose, and polysorbate 20.

Product Appearance and Container Contents

• Kadcyla is a lyophilized powder for concentrate for solution for infusion, white to off-white in color, supplied in glass vials.
• Kadcyla is available in packs of 1 vial.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639 Grenzach-Wyhlen

Germany

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

Date of Last Revision of this Leaflet

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.

This information is intended only for healthcare professionals:

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

Kadcyla must be reconstituted and diluted by a healthcare professional and administered by intravenous infusion. It should not be administered by pulse or bolus intravenous injection.

Always keep this medication in its original closed container, at a temperature of 2°C - 8°C in the refrigerator. The reconstituted Kadcyla vial with water for injectable preparations (not supplied) is stable for 24 hours at 2°C - 8°C after reconstitution and should not be frozen.

Appropriate aseptic methods should be used. Suitable procedures for the preparation of chemotherapeutic medications should be employed.

The reconstituted Kadcyla solution should be diluted in polyvinyl chloride (PVC) or polyolefin infusion bags without latex or PVC.

A 0.20 or 0.22 μm polyethersulfone (PES) in-line filter should be used when the concentrate for infusion is diluted in a 9 mg/ml (0.9%) sodium chloride solution for infusion.

Reconstitution Instructions

• Kadcyla 100 mg: Using a sterile syringe, slowly inject 5 ml of sterile water for injectable preparations into the 100 mg trastuzumab emtansine vial.
• Kadcyla 160 mg: Using a sterile syringe, slowly inject 8 ml of sterile water for injectable preparations into the 160 mg trastuzumab emtansine vial.
• Gently rotate the vial until the concentrate is completely dissolved. Do not shake.

The reconstituted solution should be visually inspected for the presence of particles and color changes before administration. The reconstituted solution should be free of visible particles and should be transparent to slightly opalescent, colorless to pale brown. It should not be used if it contains visible particles or is turbid or has changed color.

All unused residues should be discarded. The reconstituted solution does not contain preservatives and is for single use only.

Dilution Instructions

Determine the required volume of solution based on a dose of trastuzumab emtansine of 3.6 mg/kg body weight:

Volume(ml) = Total dose to be administered= (body weight(kg) x dose(mg/kg)) / 20(mg/ml, concentration of the reconstituted solution)

Withdraw the appropriate amount of solution from the vial and add it to a 250 ml infusion bag containing a 4.5 mg/ml (0.45%) or 9 mg/ml (0.9%) sodium chloride solution for infusion. Do not use glucose (5%) solutions. When dilution is performed in a 4.5 mg/ml (0.45%) sodium chloride solution for infusion, a 0.20 or 0.22 μm polyethersulfone (PES) in-line filter is not required. However, a 0.20 or 0.22 μm polyethersulfone (PES) in-line filter is necessary when using a 9 mg/ml (0.9%) sodium chloride solution for infusion. Once the infusion is prepared, it should be administered immediately. Do not freeze or shake the infusion during storage. If the dilution is performed under aseptic conditions, it can be stored for up to 24 hours at a temperature between 2°C and 8°C.