Prospect: Information for the User

Kadcyla 100mg powder for concentrate for solution for infusion

Kadcyla 160mg powder for concentrate for solution for infusion

trastuzumab emtansina

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

1.What Kadcyla is and for what it is used

2.What you need to know before Kadcyla is administered to you

3.How Kadcyla is administered to you

4.Possible adverse effects

5.Storage of Kadcyla

6.Contents of the package and additional information

What is Kadcyla

Kadcyla contains the active ingredient trastuzumab emtansine, which is formed by two parts that are linked:

• trastuzumab – a monoclonal antibody that selectively binds to an antigen (a protein on which the medication acts) 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 – a cancer-fighting substance that is activated once Kadcyla enters the cancer cell.

How is Kadcyla used

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 analyze your cancer cells to find out.
• you have already been given the medication trastuzumab and a medication from the 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 to be administered after surgery (the treatment after surgery is called adjuvant therapy).

Do not administer Kadcyla

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

If you meet the above condition, do not administer Kadcyla. If you are unsure, consult your doctor or nurse before Kadcyla is administered to you.

Warnings and precautions

Consult your doctor or nurse before Kadcyla is administered to you if:

• you have ever experienced a severe reaction related to infusion during treatment with trastuzumab characterized by symptoms such as redness, chills, fever, shortness of breath, difficulty breathing, rapid heartbeat, or decreased blood pressure.
• you are receiving treatment with medications 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 you meet any of the above conditions (or are unsure), consult your doctor or pharmacist before Kadcyla is administered to you.

Monitoring of adverse effects

Kadcyla may worsen existing conditions or produce adverse effects. See section 4 for more detailed information on adverse effects to monitor.

Inform your doctor or nurse immediately if you experience any of the following severe adverse effects while receiving Kadcyla:

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

• Liver problems:Kadcyla may cause inflammation or damage to liver cells, which can cause your liver to stop functioning normally. When liver cells are inflamed or damaged, they can release a higher-than-normal amount of specific substances (liver enzymes) into the blood, which can cause liver enzymes to be elevated in blood tests. In most cases, you will not have any symptoms. One possible symptom is 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.

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

• Cardiac problems:Kadcyla may weaken the heart muscle. When the heart muscle is weakened, you may experience symptoms such as shortness of breath at rest or while sleeping, chest pain, swelling of the legs or arms, or a sensation of rapid or irregular heartbeat. Your doctor will check your heart function before starting treatment and regularly during treatment. If you experience any of the above symptoms, inform your doctor immediately.

• Infusion-related reactions or allergic reactions:Kadcyla may cause redness, chills, fever, difficulty breathing, decreased blood pressure, rapid heartbeat, sudden swelling of the face or tongue, or difficulty swallowing, during or after the first infusion of treatment. Your doctor or nurse will check if you experience any of these adverse effects. If you develop a reaction, your infusion rate will be decreased or stopped, and you may receive treatment to counteract the adverse effects. Infusion may continue after symptoms improve.

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

• Neurological problems:Kadcyla may cause nerve damage. Symptoms you may experience include tingling, pain, numbness, itching, prickling, or muscle cramps in your hands and feet. Your doctor will monitor you to detect signs and symptoms of neurological problems.

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

Inform your doctor or nurse immediately if you experience any of the adverse 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 medications and Kadcyla

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication.

Particularly, consult your doctor or pharmacist if you are taking:

• medications that thin the blood, such as warfarin or aspirin
• medications for fungal infections, such as ketoconazole, itraconazole, or voriconazole
• antibiotics for infections, such as clarithromycin or telithromycin
• medications for HIV, such as atazanavir, indinavir, nelfinavir, ritonavir, or saquinavir
• a medication for depression called nefazodone

If you meet any of the above conditions (or are unsure), consult your doctor or pharmacist before Kadcyla is administered to you.

Pregnancy

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

• Inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.
• You must use an effective contraceptive method to avoid becoming pregnant during treatment with Kadcyla. Consult your doctor to recommend the most suitable contraceptive method for you.
• You must continue using the contraceptive method for at least 7 months after your last dose of Kadcyla. Consult your doctor before stopping your contraceptive method.
• Male patients or their female partners must also use an effective contraceptive method.
• Inform your doctor immediately if you become pregnant during treatment with Kadcyla.

Lactation

You should not breastfeed during treatment with Kadcyla and for 7 months after your last infusion of Kadcyla. It is unknown whether the components of Kadcyla pass into breast milk. Consult your doctor.

Driving and using machines

Kadcyla is not expected to affect your ability to drive, ride a bike, or use tools or machines. If you experience redness, chills, fever, difficulty breathing, decreased blood pressure, or rapid heartbeat (infusion-related reactions), blurred vision, fatigue, headache, or dizziness, do not drive, ride a bike, or use tools and machines until these symptoms disappear.

Important information about one of the components of Kadcyla

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

A doctor or nurse will administer Kadcyla in a hospital or clinic.

• It is administered through an intravenous infusion.
• You will receive an infusion every 3 weeks.

What dose of medication will be administered

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

What to do if you forget to use Kadcyla

If you forget or miss an appointment to receive Kadcyla, schedule another appointment as soon as possible. Do not wait until your next scheduled appointment.

What to do if you interrupt treatment with Kadcyla

Do not stop using this medication without first consulting your doctor.

If you have any other questions about using this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform 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 causes elevated liver enzymes in blood tests. However, in most cases observed during Kadcyla treatment, these elevations are mild and temporary, do not cause symptoms, and do not affect liver function.
• Cardinal and spontaneous hemorrhages (such as nosebleeds).
• Tickling, pain, numbness, itching, tingling, or muscle cramps in the hands and feet. These symptoms may indicate nerve damage.

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

• Redness, chills, fever, difficulty breathing, decreased blood pressure, or rapid heart rate, during or up to 24 hours after infusion administration. These are called infusion-related reactions.
• Cardiac problems may occur. Most patients will not have symptoms of cardiac problems. If symptoms occur, they may include cough, shortness of breath at rest or while sleeping in a horizontal position, chest pain, and swelling of the legs or arms, sensation of rapid or irregular heartbeat.

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

• Lung inflammation that may cause breathing problems, such as shortness of breath (at rest or while performing any activity), cough, or dry cough, 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 severe cases, they may include facial or tongue inflammation, difficulty swallowing, or difficulty breathing.

Unknown frequency:

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

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

Other side effects

Very common:

• Decreased red blood cell count (shown in a blood test)
• Nausea (vomiting)
• Diarrhea
• Dry mouth
• Urinary tract infection
• Constipation
• Abdominal pain
• Cough
• Difficulty breathing
• Mouth inflammation
• Difficulty sleeping
• Muscle or joint pain
• Fever
• Headache
• Fatigue
• Weakness

Common:

• Chills or flu-like symptoms
• Decreased potassium levels (shown in a blood test)
• Skin rash
• Decreased white blood cell count (shown in a blood test)
• Dry eyes, watery eyes, or blurred vision
• Red or infected eyes
• Indigestion
• Leg and/or arm inflammation
• Gum bleeding
• Increased blood pressure
• Dizziness
• Altered taste
• Itching
• Difficulty remembering
• Hair loss
• Hand and foot reaction (palmar-plantar erythrodysesthesia syndrome)
• Nail changes

Uncommon:

• Another anomaly that Kadcyla may cause is a condition known as nodular regenerative hyperplasia of the liver. This anomaly causes changes in liver structure. Patients who develop this anomaly develop multiple nodules in the liver that may affect liver function. Over time, symptoms may include a feeling of fullness or swelling of the abdomen due to fluid accumulation or bleeding from the formation of abnormal blood vessels in the esophagus or rectum.
• During Kadcyla infusion, the lost perfusion fluid may cause pain to the touch or skin irritation or inflammation in the area of infusion administration.

If you experience any of the above side effects after stopping Kadcyla treatment, consult your doctor or nurse and inform them that you have been treated with Kadcyla.

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging and vial after CAD. The expiration date is the last day of the month indicated.
• Store in the refrigerator (between 2°C and 8°C). Do not freeze.
• Once the solution for infusion has been 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 thrown away through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help to protect the environment.

Composition of Kadcyla

• 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 vial of 5 ml 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, a vial of 8 ml 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 polisorbato 20.

Appearance of the product and contents of the pack

• Kadcyla is a lyophilized powder for concentrate for solution for infusion of white to off-white color that is 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 responsible

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639 Grenzach-Wyhlen

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

This information is intended solely for medical professionals:

To avoid medication errors, it is essential to check the labels on 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 deruxtecan).

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

Always keep this medicinal product in its original packaging, at a temperature of 2°C - 8°C in a refrigerator. The vial of Kadcyla reconstituted with water for injections (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. Appropriate procedures for the preparation of chemotherapeutic agents should be employed.

The reconstituted solution of Kadcyla should be diluted in PVC or polyolefin bags without latex or PVC.

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

Instructions for reconstitution

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

The reconstituted solution should be visually inspected for the presence of particles and changes in color 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 if it is turbid or has changed color.

Any unused residue should be discarded. The reconstituted solution does not contain preservatives and is for single use.

Instructions for dilution

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

Volume(ml)=Dose to be administered= (Body weight(kg) xDose(mg/kg))

20(mg/ml, concentration of the reconstituted solution)

Withdraw the appropriate amount of solution from the vial and add to a 250 ml infusion bag containing a solution of 4.5 mg/ml (0.45%) or 9 mg/ml (0.9%) sodium chloride for infusion. Do not use glucose solutions (5%). When the dilution is performed in a solution of 4.5 mg/ml (0.45%) sodium chloride for infusion, a filter in-line of polyethersulfone (PES) 0.20 or 0.22 μm is not required. However, the use of a filter in-line of polyethersulfone (PES) 0.20 or 0.22 μm is necessary when using a solution of 9 mg/ml (0.9%) sodium chloride for infusion. Once the infusion is prepared, it should be administered immediately. Do not freeze or agitate the infusion during storage.

If the dilution has been performed under aseptic conditions, it can be stored for a maximum of 24 hours at a temperature between 2°C and 8°C.