Mylotarg: detailed information

Patient Information Leaflet: Information for the User

MYLOTARG 5 mg powder for concentrate for solution for infusion

gemtuzumab ozogamicin
Please read all of 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 or nurse.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

What MYLOTARG is and what it is used for
What you need to know before receiving MYLOTARG
How MYLOTARG is given
Possible side effects
How to store MYLOTARG
Contents of the pack and other information

1. What MYLOTARG is and what it is used for

MYLOTARG contains the active substance gemtuzumab ozogamicin, an antineoplastic medicinal product composed of a monoclonal antibody linked to a substance designed to kill tumour cells. This substance is delivered to tumour cells by the monoclonal antibody. A monoclonal antibody is a protein that recognises certain tumour cells.
MYLOTARG is used to treat a certain type of blood cancer called acute myeloid leukaemia (AML), in which the bone marrow produces abnormal white blood cells. MYLOTARG is intended for the treatment of AML in patients aged 15 years and older who have not received prior treatment. MYLOTARG is not intended for use in patients with a type of cancer called acute promyelocytic leukaemia (APL).

2. What you need to know before using MYLOTARG

Do not use MYLOTARG if:

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

Warnings and precautions
When you receive this medicine for the first time and during the treatment cycle, inform your doctor
or nurse if:

you have or have previously had liver problems: MYLOTARG may cause, during or after treatment, a potentially life-threatening condition called hepatic veno-occlusive disease, in which blood vessels in the liver become damaged and blocked by blood clots, possibly leading to fluid retention, rapid weight gain, enlargement of the liver (which may be painful), and ascites (excessive accumulation of fluid in the abdominal cavity).
allergic reaction: you experience a high-pitched sound during breathing (wheezing), have difficulty breathing, shortness of breath, or cough with or without mucus, hives, itching, swelling, or feel feverish 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, develop chills or shaking, feel warm or have a fever. Some infections may be serious and potentially fatal.
bleeding: you experience unusual bleeding, bleeding from the gums, bruise easily, or have recurrent nosebleeds.
anaemia: you have headache, feel tired, dizzy, or look pale.
infusion reaction: during or immediately after the infusion of MYLOTARG you experience symptoms such as dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances (this may be a potentially life-threatening complication known as tumour lysis syndrome).

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

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

Pregnancy, breast-feeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breast-feeding,
ask your doctor or nurse for advice before this medicine is administered to you.
You must avoid becoming pregnant or fathering a child due to the potential adverse effects on the
unborn child. Women must use two effective methods of contraception during treatment and for at least
7 months after the last dose. Men must use two effective methods of contraception during treatment and for at least 4 months after the last dose. Contact your doctor immediately if you or your partner become pregnant during treatment with this medicine.
Seek medical advice regarding fertility preservation before starting treatment.
If you need to be treated with MYLOTARG, you must stop breast-feeding during treatment and for at least 1 month after treatment. Consult your doctor.

Driving and using machines
If you experience unusual tiredness, dizziness, or headache (these are very common side effects of MYLOTARG), you must not drive or operate machinery.

MYLOTARG contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially "sodium-free".

3. How to use MYLOTARG

A doctor or nurse will administer MYLOTARG to you through an intravenous infusion (IV infusion) gradually over 2 hours.
Your doctor will determine the correct dose.
Your doctor or nurse may adjust the dose, suspend it, or completely stop treatment with MYLOTARG if you experience certain side effects.
Your doctor may reduce the dose based on your response to treatment.
Your doctor will perform blood tests during treatment to monitor for side effects and response to therapy.
Before receiving MYLOTARG, you will be given medications to help reduce symptoms such as fever and chills, known as infusion reactions, during or shortly after the MYLOTARG infusion.

If you have any questions about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some of these side effects can be serious and may occur during or after treatment with MYLOTARG. Contact 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 taking MYLOTARG”):

Liver problems Contact your doctor immediately if you experience a rapid weight gain, feel pain in the upper right part of your abdomen, or have fluid accumulation causing abdominal swelling. Your doctor may perform blood tests and detect abnormalities in liver-specific blood parameters, which could be signs of a life-threatening condition called hepatic veno-occlusive disease.
Bleeding (sign of a low number of blood cells called platelets) Contact your doctor immediately if you bruise easily or have frequent nosebleeds, or if you pass black, tarry stools, cough up blood, have blood in your sputum, or experience dizziness, fainting, or confusion.
Infections (signs of a low number of white blood cells called neutrophils) Some infections can be serious and may be caused by viruses, bacteria, or other factors that could be life-threatening.
A complication known as tumor lysis syndrome Contact your doctor immediately if you experience dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances.
Infusion reactions Medicines of this type (monoclonal antibodies) can cause infusion reactions such as rash, shortness of breath, difficulty breathing, tightness in the chest, chills, or fever, and back pain.

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

Infections (including serious infections)
Reduced number of platelets (which help blood to clot) in the blood
Reduced number of white blood cells, which may cause general weakness and increased susceptibility to infections
Reduced number of red blood cells (anaemia), which may cause fatigue and shortness of breath
High blood sugar levels
Reduced appetite
Headache
Rapid heartbeat
Bleeding
Low blood pressure
High blood pressure
Shortness of breath
Vomiting
Diarrhoea
Abdominal pain
Feeling unwell (nausea)
Inflammation of the mouth
Constipation
Abnormal liver blood parameters (which may indicate liver damage)
Rash
Fever
Oedema (excess fluid in body tissues, causing swelling of hands and feet)
Tiredness
Chills
Changes in blood levels of various enzymes (may be detected in blood tests)
Prolonged blood clotting time (which may lead to prolonged bleeding)
Excess uric acid in the blood

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

Signs of an infusion reaction, such as rash, shortness of breath, difficulty breathing, tightness in the chest, chills or fever, back pain during or after MYLOTARG infusion
Signs of liver enlargement (hepatomegaly), such as a swollen abdomen
Excessive accumulation of fluid in the abdomen/stomach
Indigestion
Inflammation of the oesophagus (swallowing tube)
Hepatic veno-occlusive disease (VOD), which includes signs of liver enlargement, pain in the upper right part of the abdomen, yellowing of the skin and whites of the eyes, fluid accumulation in the abdomen, weight gain, and abnormal liver-specific blood parameters
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, abnormal enlargement of the liver, and/or fluid accumulation in the abdomen associated with blood clots in the liver. Symptoms may also include feeling unwell (nausea) and/or vomiting.

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

Interstitial pneumonia (lung inflammation causing cough and difficulty breathing)
Inflammation of the intestine associated with decreased white blood cell count
Inflammation of the urinary bladder leading to bleeding from the bladder

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via 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 MYLOTARG

MYLOTARG will be stored by healthcare professionals at the hospital or clinic.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the carton after EXP. The expiry date refers to the last day of that month.
Unopened vial: Store in the refrigerator (2°C - 8°C). Do not freeze. Keep the vial in its original packaging to protect it from light.
Reconstituted and diluted solution: Protect reconstituted and diluted MYLOTARG solutions from light. The solutions must be used immediately. Do not freeze the reconstituted or diluted solution.
If immediate use is not possible:

After reconstitution, the original vial may be stored for up to 16 hours in the refrigerator (2°C - 8°C) or for no more than 3 hours at room temperature (below 30°C).
The diluted solution may be stored for up to 18 hours in the refrigerator (2°C - 8°C) and for no more than 6 hours at room temperature (below 30°C). The permitted storage time at room temperature (below 30°C) includes the time required for preparation of the diluted solution, equilibration if needed, 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 the presence of particles or any change in colour before administration.
Do not dispose of any medicine via wastewater or household waste. Ask your doctor how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MYLOTARG contains

The active substance is gemtuzumab ozogamicin.
One vial contains 5 mg of 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, monosodium dihydrogen phosphate monohydrate, and anhydrous disodium hydrogen phosphate. See section 2, “MYLOTARG contains sodium”.

Description of the appearance of MYLOTARG and contents of the pack
MYLOTARG is a powder for concentrate for solution for infusion. It is supplied as a tablet or
white to off-white powder.
Each carton contains 1 amber glass vial with a rubber stopper, screw cap, and protective cap.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Service Company BV
Hoge Wei 10
1930, Zaventem
Belgium

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

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel: + 370 52 51 4000
Tél/Tel: +32 (0)2 554 62 11

България Magyarország
Пфайзер Люксембург САРЛ, Клон Pfizer Kft.
България Tel: +36-1-488-37-00
Тел.: +359 2 970 4333

Česká republika Malta
Pfizer, spol. s r.o. Vivian Corporation Ltd.
Tel: +420 283 004 111 Tel: + 35621 344610

Danmark Nederland
Pfizer ApS Pfizer bv
Tlf: +45 44 20 11 00 Tel: +31 (0) 800 63 34 636

Deutschland Norge
PFIZER PHARMA Pfizer AS
GmbH Tlf: +47 67 52 61 00
Tel: +49 (0)30 550055 51000

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
Pfizer Ελλάς A.E. Pfizer Polska Sp. z o.o.
Τηλ: +30 210 6785 800 Tel: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Tel: +34 91 490 99 00 Tel: +351 21 423 5500

France România
Pfizer Pfizer Romania S.R.L.
Tel: +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL
Tel: + 385 1 3908 777 Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0)1 52 11 400

Ireland Slovenská republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: 1800 633 363 (toll free) Tel: + 421 2 3355 5500
+44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh/Tel: +358 (0)9 43 00 40

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550-520 00

Κύπρος United Kingdom (Northern Ireland)
Pfizer Ελλάς Α.Ε. (Cyprus Branch) Pfizer Limited
Τηλ: +357 22 817690 Tel: +44 (0) 1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: + 371 670 35 775

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended for healthcare professionals only:

Use proper aseptic technique during reconstitution and dilution procedures. MYLOTARG is light-sensitive and must be protected from ultraviolet light during reconstitution, dilution, and administration.

Reconstitution

Calculate the required dose (mg) of MYLOTARG.
Prior to 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 gemtuzumab ozogamicin.
Gently rotate the vial to aid dissolution. Do not shake.
Inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution may contain small white to off-white, opaque to translucent, amorphous to fibril-like particles.
MYLOTARG does not contain bacteriostatic preservatives.
If the reconstituted solution cannot be used immediately, it may be stored in the original vial for up to 16 hours in a refrigerator (2°C – 8°C) or up to 3 hours at room temperature (below 30°C). Protect from light and do not freeze.

Dilution

Calculate the volume of reconstituted solution required to achieve the appropriate dose based on the patient’s body surface area. Withdraw this volume from the vials using a syringe. Mylotarg vials contain 5 mg of medicinal product without overfill. When reconstituted to a concentration of 1 mg/mL as directed, the extractable volume per vial is 4.5 mg (4.5 mL). Protect from light. Discard any unused reconstituted solution remaining in the vial.
Doses must be diluted to a concentration between 0.075 mg/mL and 0.234 mg/mL according to the following instructions:
o Doses below 3.9 mg must be prepared for administration via syringe. Add the reconstituted MYLOTARG solution to a syringe containing 9 mg/mL (0.9%) Sodium Chloride Solution for Injections to achieve a final concentration between 0.075 mg/mL and 0.234 mg/mL. Protect from light.
o Doses equal to or greater than 3.9 mg must be diluted in a syringe or intravenous infusion bag with an appropriate volume of 9 mg/mL (0.9%) Sodium Chloride Solution for Injections 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 9 mg/mL (0.9%) Sodium Chloride Solution for Injections, the MYLOTARG solution should be administered immediately. If immediate use is not possible, the diluted solution may be stored for up to 18 hours in a refrigerator (2°C – 8°C) or up to 6 hours at room temperature (below 30°C). The permitted room temperature storage time (below 30°C) includes the time required for preparation of the diluted solution, equilibration if needed, and administration to the patient. The maximum time from preparation to administration must 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

The diluted solution must be filtered. A 0.2 micron in-line filter made of polyethersulfone (PES) with low protein-binding capacity must be used for MYLOTARG infusion.
Doses administered via syringe must use small-bore infusion lines with an in-line 0.2 micron polyethersulfone (PES) filter with low protein-binding capacity.
During infusion, the infusion bag or syringes for intravenous administration must be protected from light using an appropriate protective cover (including ultraviolet light). The infusion line does not need to be protected from light.
Infuse the diluted solution over 2 hours. The infusion must be completed within 6 hours, which is the maximum permitted storage time of the diluted solution at room temperature (below 30°C).
PVC infusion lines (with or without DEHP), polyurethane, or polyethylene lines are recommended.

MYLOTARG must not be mixed or co-administered by infusion with other medicinal products.

Disposal

Disposal procedures for toxic waste as prescribed for antineoplastic medicinal products must be followed.