Patient Information Leaflet: Package Insert

Tomudex 2 mg Powder for Solution for Infusion

Raltitrexed

Read this entire leaflet carefully before you start using this medicine, because it contains important information for you.

-Keep this leaflet, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist or nurse.

-If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1.What is Tomudex and what it is used for

2.What you need to know before starting to use Tomudex

3.How to use Tomudex

4.Possible side effects

5.Storage of Tomudex

6. Contents of the pack and additional information

Tomudex is used for the treatmentpalliative of advanced colorectal cancer, which affects the colon and rectum (parts of your large intestine), when 5FU+LV therapy is unacceptable or inappropriate.

Do not use Tomudex:

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).
• Before being treated with this medication, you must inform your doctor if you are, or suspect you are, pregnant or breastfeeding, as Tomudex should not be administered in these cases.
• This medication should not be administered to children.
• This medication should not be administered to patients with severe kidney disease.
• This medication should not be administered with leucovorin (folic acid), folic acid, or vitamin preparations containing these compounds.

Warnings and precautions:

Consult your doctor, pharmacist, or nurse before starting to use Tomudex.

• If you and your partner wish to have children; it is recommended to avoid pregnancy during treatment and for at least 6 months after its completion, if either member of the couple is being treated with Tomudex.
• If you have or have had any blood, renal, or hepatic problems.
• If you have or have had any stomach or intestine problems.
• If you have previously received radiation therapy (high-dose X-ray treatment).

Children and adolescents:

See “Do not use Tomudex”

Other medications and Tomudex:

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.Especially, if you are taking folic acid or folinic acid, vitamins, or vitamin supplements, or if you are taking an anticoagulant (blood clot prevention medication).

Pregnancy, breastfeeding, and fertility:

If you are pregnant or breastfeeding,or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Before starting treatment with this medication, a possible pregnancy must be ruled out.

Pregnancy should be avoided if a member of the couple is being treated with this medication; similarly, it is recommended to avoid pregnancy for at least 6 months after completing treatment.

Tomudex should not be administered during pregnancy, nor in women who may become pregnant during treatment with this medication.

Breastfeeding

This medication should not be administered during breastfeeding.

Fertility

Fertility studies in rats indicate that raltitrexed may cause a decrease in male fertility. Fertility returned to normal 3 months after the end of administration.

Use in elderly patients:

Elderly patients are more vulnerable to the toxic effects of Tomudex. As renal function tends to deteriorate with age, there is a risk of accumulation of this compound in elderly patients. It is essential to exercise extreme caution to ensure adequate monitoring of adverse reactions.

Driving and operating machinery:

It is unlikely that this medication will adversely affect your ability to drive a vehicle or operate machinery. However, some patients may experience a flu-like syndrome, or a general state of discomfort, for a short time after being treated with this medication. If you experience these effects, you should not drive or operate machinery.

Tomudex contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial; it is essentially “sodium-free”.

Followexactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again

Your doctor will inform you of the duration of your treatment withthis medication. Do not discontinue treatment before your doctor tells you to.

• Your injection will be administered under the supervision of a specialist doctor in the use of this type of medication.
• If you are unsure about any specific aspect, ask your doctor.
• The exact dose that will be administered to you will be decided by your doctor. This will vary depending on your body size and how you react to the treatment. The results of your blood tests will also help the doctor decide on the dose you will receive.
• The usual dose is 3 mg/m2of body surface area (you will be given 3 mg for every square meter of body surface area, calculated from your height and weight).

• The dose you receive may vary between treatments.
• Tomudex will be injected slowly into one of your veins. The administration of the injection will usually take 15 minutes.

The medication is usually administered every 3 weeks. This period may be extended depending on the results of your regular blood tests

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

Some of these must be treatedimmediately. If you experience any of the following, contact your doctor (specialist) immediately to receive treatment if necessary:

Very common side effects (may affect more than 1 in 10 patients) include:

-Diarrhea

-Vomiting

-Fever

Common side effects (may affect up to 1 in 10 patients) include:

Infections

-Mouth ulceration or stomatitis (mouth pain)

Other possible side effects are:

Very common side effects (may affect more than 1 in 10 patients) include:

-Loss of appetite

-Leucopenia (low blood cell count)

-Anemia

-Nausea

-Constipation

-Abdominal pain

-Skin effects (red or peeling skin or itchy rash)

-Weakness (sometimes similar to flu-like symptoms)

-Mucositis (inflammation of the mouth and intestines causing mouth pain or ulceration or diarrhea)

-Liver changes

Common side effects (may affect up to 1 in 10 patients) include:

-Celulitis (skin swelling and redness)

-Infection

-Flu-like symptoms

-Low platelet count

-Dehydration (feeling thirsty and/or dry skin)

-Headache

-Muscle cramps

-Alteration of taste

-Conjunctivitis (red or itchy eyes)

-Hair loss

-Itching skin

-Sweating

-Joint pain

-Swelling, pain, and discomfort at the injection site

-Weight loss

In addition, this medicine may cause blood changes, due to its effects on your bone marrow or liver. Your doctor will perform regular blood tests to detect any abnormalities.

Do not be alarmed by this list of possible side effects, as you may not experience any of them.

Inform your doctor if you think you have any of these or any other problem with your treatment.

If you observe any other reaction not described in this prospectus, consult your doctor or pharmacist.

Reporting side effects:

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial label and on the outer packaging after CAD. The expiration date is the last day of the month indicated.

Store below 25C. Store the vial in the outer packaging

The injection will normally be stored in the hospital. The personnel are responsible for the correct storage, use, and disposal of the medication.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

After reconstitution, see the sectionINFORMATION FOR HEALTHCARE PROFESSIONALSat the end of this leaflet.

Composition of Tomudex

• The active ingredient is raltitrexed. Each vial of powder contains 2 mg of raltitrexed.
• The other components are: mannitol, sodium phosphate dibasic (heptahydrate) and sodium hydroxide.

Appearance of the product and contents of the package

Tomudex is a white to off-white powder.

Each package contains a transparent glass vial with 2 mg of powder, with a rubber stopper and an aluminum seal.

Marketing authorization holder and manufacturer

The marketing authorization holder is:

HOSPIRA INVICTA, S.A.

Avda. de Europa 20-B - Parque Empresarial La Moraleja

28108-Alcobendas (Madrid)

Spain

The manufacturer is:

Pfizer Service Company BV

Hoge Wei 10,

1930 Zaventem,

Belgium

Last review date of this leaflet: November 2021

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

The following information is intended only for healthcare professionals

INFORMATION FOR HEALTHCARE PROFESSIONALS.

INSTRUCTIONS FOR CORRECT ADMINISTRATION

Each vial, containing 2 mg of raltitrexed, must be reconstituted with 4 ml of water for injection to provide a solution of 0.5 mg/ml of raltitrexed. The appropriate dose of the solution is prepared by diluting in 50-250 ml of sodium chloride 9 mg/ml (0.9%) or glucose (dextrose) 50 mg/ml (5%) solution and administered by intravenous infusion over a period of 15 minutes.

Tomudex or the specified solutions for reconstitution or dilution do not contain bacteriostatic agents or preservatives, therefore, it must be reconstituted and diluted under aseptic conditions, recommending that the Tomudex solutions be used as soon as possible. The reconstituted solution must be stored under refrigeration (2°-8°C) for a period of up to 24 hours.

According to established standards, when the medication is diluted in sodium chloride 9 mg/ml (0.9%) or glucose (dextrose) 50 mg/ml (5%) solution, it is recommended to administer the reconstituted solution as soon as possible. The reconstituted solution must be used completely or discarded within 24 hours after reconstitution of the intravenous injection.

The reconstituted and diluted solutions do not require protection from light.

Do not store, used vials or reconstituted solutions, for future administrations. Any unused injection or reconstituted solution should be discarded, as recommended for cytotoxic products.

The injection of Tomudex must be reconstituted by trained personnel in a designated area for the reconstitution of cytotoxic products. These preparations should not be handled by pregnant women.

The reconstitution should be performed normally in an area (separate installation) with extraction, for example, laminar flow cabinet, and the working surfaces must be protected with disposable paper, absorbent, and plastic backing.

Appropriate protective clothing, including standard surgical gloves, disposable, and glasses, should be used. In case of skin contact, wash immediately and thoroughly with water, and in case of eye splash, wash with clean water for at least 10 minutes, separating the eyelids, and consult a doctor.

If spilled, it should be cleaned up using standard procedures.

The waste material must be disposed of by incineration, in accordance with the established procedures for the handling of cytotoxic agents.