MYLOTARG 5 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

MYLOTARG 5mg powder for concentrate for solution for infusion

gemtuzumab ozogamicin

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 or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What MYLOTARG is and what it is used for

MYLOTARG contains the active substance gemtuzumab ozogamicin, a cancer medicine that consists of a monoclonal antibody linked to a substance intended to eliminate cancer cells. This substance is distributed to cancer cells through the monoclonal antibody. A monoclonal antibody is a protein that recognizes certain cancer cells.

MYLOTARG is used to treat a certain type of blood cancer called acute myeloid leukemia (AML) in which the bone marrow produces abnormal white blood cells. MYLOTARG is indicated for the treatment of AML in patients aged 15 years and older who have not had other treatments. MYLOTARG must not be used in patients with a type of cancer called acute promyelocytic leukemia (APL).

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

You must not be given MYLOTARG if:

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

Warnings and precautions

The first time you receive this medicine and during the course of treatment, tell your doctor or nurse if:

• you have or have ever had liver problems:MYLOTARG may cause, during or after treatment, a potentially life-threatening condition called hepatic veno-occlusive disease, in which the blood vessels of the liver are damaged and blocked due to the formation of blood clots and which may lead to fluid retention, rapid weight gain, liver enlargement (which may be painful) and ascites (excessive fluid accumulation in the abdominal cavity).
• allergic reaction:you experience wheezing during breathing (wheezing), difficulty breathing, shortness of breath or cough with or without mucus, hives, itching, swelling or feeling of fever and chills (signs of an infusion-related reaction) during or shortly after the infusion of MYLOTARG.
• infection:you have or think you have an infection, have chills or shivers, have a feeling of heat or have a fever. Some infections can be serious and potentially life-threatening.
• bleeding:you have unusual bleeding, your gums bleed, you bruise easily or have frequent nosebleeds.
• anemia:you have headaches, feel tired, feel dizzy or are pale.
• infusion reaction:you experience during or shortly after the infusion of MYLOTARG symptoms such as dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath or heart rhythm disturbances (this may be a potentially life-threatening complication known as tumor lysis syndrome).

Children and adolescents

MYLOTARG must not be used in children and adolescents under 15 years of age, as the available data are limited in this population.

Other medicines and MYLOTARG

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal remedies.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before using this medicine.

Avoid becoming pregnant or conceiving a child due to the potential side effects on the child. Women must use 2 effective methods of contraception during treatment and for at least 7 months after the last dose of treatment. Men must use 2 effective methods of contraception during treatment and for at least 4 months after the last dose of treatment. Contact your doctor immediately if you or your partner become pregnant while taking this medicine.

Ask for information about fertility preservation before treatment.

If you need to receive MYLOTARG, you will stop breastfeeding during treatment and for at least 1 month after completion. Consult your doctor.

Driving and using machines

If you feel unusually tired, dizzy or have a headache (these are very common side effects of MYLOTARG) do not drive or use machines.

MYLOTARG contains sodium

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

3. How MYLOTARG is given

• A doctor or nurse will give you MYLOTARG through a drip into your vein (intravenous infusion), gradually over 2 hours.
• Your doctor will decide the correct dose.

• Your doctor or nurse may change the dose, interrupt or completely stop treatment with MYLOTARG if you experience certain side effects.
• Your doctor may reduce the dose according to your response to treatment.
• Your doctor will perform blood tests during treatment to detect side effects and check your response to treatment.

• Before receiving MYLOTARG, you will be given other medicines to help reduce certain symptoms such as fever and chills, known as infusion reactions, during or shortly after the infusion of MYLOTARG.

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.

Some of these side effects may be serious and may occur during or after treatment with MYLOTARG. Tell your doctor or nurse immediately if you experience any of the following serious side effects (see also section 2: "What you need to know before you are given MYLOTARG"):

• Liver problemsTell your doctor immediately if you gain weight rapidly, feel pain in the upper right part of your abdomen or have fluid accumulation that causes abdominal swelling. Your doctor may perform blood tests and detect abnormalities in liver blood tests, which may be signs of a potentially life-threatening condition called hepatic veno-occlusive disease.
• Bleeding (signs of low platelet count)

Tell your doctor immediately if you bruise easily or have frequent nosebleeds, or if you have black stools, cough up blood, spit up blood, feel dizzy, faint or are confused.

• Infections (signs of low white blood cell count)

Some infections can be serious and potentially life-threatening.

• Tumor lysis syndromeTell your doctor immediately if you experience dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath or heart rhythm disturbances.

• Infusion reactionsMedicines of this type (monoclonal antibodies) may cause infusion reactions such as rash, shortness of breath, difficulty breathing, chest tightness, chills or fever, or back pain.

The side effects include:

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

• Infections (including serious infections)
• Decreased platelet count in the blood (cells that help blood clotting)
• Decreased white blood cell count, which can cause general weakness and a tendency to catch infections
• Decreased red blood cell count (anemia), which can cause fatigue and shortness of breath
• High blood sugar levels
• Decreased appetite
• Headache
• Fast heart rate
• Bleeding
• Low blood pressure
• High blood pressure
• Shortness of breath
• Vomiting
• Diarrhea
• Abdominal pain
• General malaise (nausea)
• Mouth inflammation
• Constipation
• Abnormal liver blood tests (which may be indicators of liver damage)
• Rash
• Fever
• Edema (excess fluid in body tissue, causing swelling of hands and feet)
• Fatigue
• Chills
• Changes in levels of different enzymes in the blood (may appear in blood tests)
• Prolonged coagulation time (which may cause prolonged bleeding)
• High uric acid level in the blood

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

• Signs of infusion reactions such as rash, shortness of breath, difficulty breathing, chest tightness, chills or fever, or back pain during or after the infusion of MYLOTARG
• Signs of liver enlargement (hepatomegaly), such as abdominal swelling
• Abnormal liver function
• Excessive fluid accumulation in the abdomen/stomach
• Indigestion
• Inflammation of the esophagus (food pipe)
• Hepatic veno-occlusive disease (VOD), which includes signs of liver enlargement, pain in the upper right part of the abdomen, yellowing of the skin or whites of the eyes, fluid accumulation in the abdomen, weight gain, abnormal liver tests
• Yellowing of the skin or whites of the eyes due to liver or blood problems (jaundice)
• Redness of the skin
• Itching of the skin
• Organ failure

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

• Liver failure
• Budd-Chiari syndrome, which includes pain in the upper right part of the abdomen, an abnormally large liver, and/or fluid accumulation in the abdomen associated with blood clots in the liver. The symptoms may also include general malaise (nausea) and/or vomiting.

Frequency not known (cannot be estimated from the available data):

• Interstitial pneumonia (inflammation of the lungs that causes cough and difficulty breathing)
• Inflammation of the intestine associated with low white blood cell count
• Inflammation of the bladder that causes bleeding from the bladder

Reporting of side effects

If you experience 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 in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of MYLOTARG

MYLOTARG 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 label of the vial and the carton after EXP. The expiry date is the last day of the month stated.

Unopened vial:Store in a refrigerator (between 2°C and 8°C). Do not freeze. Store in the original packaging to protect from light.

Reconstituted and diluted solution:Protect the reconstituted and diluted solutions of MYLOTARG from light. The solutions should be used immediately. Do not freeze the reconstituted or diluted solution.

If not used immediately:

• After reconstitution, the original vial can be stored for up to 16 hours in a refrigerator (between 2°C and 8°C) or up to 3 hours at room temperature (below 30°C).

• The diluted solution can be stored for up to 18 hours in a refrigerator (between 2°C and 8°C) and up to 6 hours at room temperature (below 30°C). The time allowed at room temperature (below 30°C) includes the time required for preparation of the diluted solution, equilibration if necessary, and administration. The maximum time from preparation of the diluted solution to administration must not exceed 24 hours.

Do not use this medicine if you notice 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. These measures will help protect the environment.

6. Container Contents and Additional Information

Composition of MYLOTARG

• The active ingredient is gemtuzumab ozogamicin.
• After reconstitution, each ml of the concentrated solution contains 1 mg of gemtuzumab ozogamicin.
• The other components are dextran 40, sucrose, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous. See section 2, "MYLOTARG contains sodium".

Appearance and Container Contents of the Product

MYLOTARG is a powder for concentrate for solution for infusion. It is presented as a white to off-white paste or powder.

Each container contains 1 type I amber glass vial with a rubber stopper and a flip-off cap.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer

Pfizer Service Company BV

Hoge Wei 10

1930, Zaventem

Belgium

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

Date of Last Revision of this Prospectus:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended solely for healthcare professionals:

Use appropriate aseptic technique for reconstitution and dilution procedures. MYLOTARG is sensitive to light and should be protected from ultraviolet light during reconstitution, dilution, and administration.

Reconstitution

• Calculate the dose (mg) of MYLOTARG required.
• Before reconstitution, allow the vial to reach room temperature (below 30°C) for approximately 5 minutes. Reconstitute each 5 mg vial with 5 ml of water for injections to obtain a single-use solution of 1 mg/ml of gemtuzumab ozogamicin.
• Gently swirl the vial to facilitate dissolution. Do not shake.
• Inspect the reconstituted solution for particles or discoloration. The reconstituted solution may contain small white to off-white particles, opaque to translucent, and without a defined shape or with a fiber-like shape.
• MYLOTARG does not contain bacteriostatic preservatives.
• If the reconstituted solution is not used immediately, it can be stored in the original vial for up to 16 hours in the refrigerator (between 2°C and 8°C) or up to 3 hours at room temperature (below 30°C). Protect from light and do not freeze.

Dilution

• Calculate the required volume of the reconstituted solution needed to achieve the desired dose based on the patient's body surface area. Withdraw this volume from the vial with a syringe. The MYLOTARG vials contain 5 mg of the medicinal product without overfill. When reconstituted to a concentration of 1 mg/ml as directed, the extractable content of the vial is 4.5 mg (4.5 ml). Protect from light. Discard any unused reconstituted solution remaining in the vial.
• Doses should be mixed to a concentration between 0.075 mg/ml and 0.234 mg/ml according to the following instructions:
• • Doses less than 3.9 mg should be prepared for administration with a syringe. Add the reconstituted MYLOTARG solution to a syringe with sodium chloride 9 mg/ml (0.9%) solution to a final concentration between 0.075 mg/ml and 0.234 mg/ml. Protect from light.
  • Doses greater than or equal to 3.9 mg should be diluted in a syringe or intravenous bag with an appropriate volume of sodium chloride 9 mg/ml (0.9%) solution to ensure a final concentration between 0.075 mg/ml and 0.234 mg/ml. Protect from light.
• Gently invert the infusion container to mix the diluted solution. Do not shake.
• After dilution with sodium chloride 9 mg/ml (0.9%) solution, the MYLOTARG solution should be infused immediately. If not used immediately, the diluted solution can be stored for up to 18 hours in the refrigerator (between 2°C and 8°C) and up to 6 hours at room temperature (below 30°C). The time allowed at room temperature (below 30°C) includes the time required for preparation of the diluted solution, equilibration if necessary, and administration to the patient. The maximum time from preparation of the diluted solution to administration should not exceed 24 hours. Protect from light and do not freeze.
• It is recommended that the infusion container be made of polyvinyl chloride (PVC) with DEHP, ethylene-vinyl acetate (EVA), or polyolefin (polypropylene and/or polyethylene).

Administration

• Filtering of the diluted solution is required. For infusion of MYLOTARG, a 0.2 microns protein-binding low polyethersulfone (PES) filter in line should be used.
• Doses administered with a syringe should use small-caliber (microbore) infusion lines with a 0.2 microns protein-binding low polyethersulfone (PES) filter in line.
• During infusion, the intravenous bag or syringes should be protected from light (including ultraviolet light) with a cover that blocks light entry. It is not necessary to protect the infusion line from light.
• Infuse the diluted solution over 2 hours. The infusion should be completed before the end of the permitted 6-hour storage period of the diluted solution at room temperature (below 30°C).
• It is recommended that the infusion lines be made of PVC (with or without DEHP), polyurethane, or polyethylene.

Do not mix or administer MYLOTARG in infusion with other medicinal products.

Disposal

• Use established procedures for the disposal of toxic waste for anticancer medicinal products.