TOPOTECAN ACCORD 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

1. What is Topotecan Accord and what is it used for

Topotecan Accord helps to get rid of tumors. A doctor or nurse will give you the medicine through a vein in your arm in the hospital.

Topotecan Accord is used to treat:

• ovarian cancer or small cell lung cancerthat has come back after chemotherapy.
• advanced cancer of the cervixif surgery or radiotherapy is not possible. When treating cancer of the cervix, Topotecan Accord is given in combination with another medicine called cisplatin.

Your doctor will decide with you whether Topotecan Accord is better than continuing treatment with your initial chemotherapy.

2. What you need to know before you use Topotecan Accord

You should not be givenTopotecan Accord

• if you are allergic to topotecan or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding.
• if your blood cell count is too low. Your doctor will tell you if this is the case, based on your latest blood test results.

Tell your doctorif you are in any of these situations.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given this medicine:

• if you have kidney or liver problems. It may be necessary to adjust the dose of Topotecan Accord.
• if you are pregnant or planning to become pregnant. See the section below on “Pregnancy, breast-feeding and fertility”.
• if you are a male and plan to father a child. See the section below on “Pregnancy, breast-feeding and fertility”.

Tell your doctorif you are in any of these situations.

Other medicines and Topotecan Accord

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription or any herbal medicines.

Pregnancy, breast-feeding and fertility

Topotecan Accord should not be given to pregnant women. It may harm the baby before, during or after birth. You must use an effective method of contraception. Ask your doctor for advice. Do not try to become pregnant until your doctor tells you it is safe to do so.

Male patients who wish to father a child should ask their doctor for advice on family planning or treatment. If your partner becomes pregnant during your treatment, tell your doctor immediately.

Do not breast-feed if you are being treated with Topotecan Accord. Do not restart breast-feeding until your doctor tells you it is safe to do so.

Driving and using machines

Topotecan Accord may cause tiredness.

If you feel tired or weak, do not drive or use machinery.

Topotecan Accord contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially “sodium-free”. If your doctor uses a saline solution to dilute Topotecan Accord, the amount of sodium you receive will be higher.

3. How to use Topotecan Accord

Your doctor will calculate the dose of Topotecan Accord that you will be given based on:

• your body size (surface area measured in square meters)
• the results of your blood tests before treatment
• the disease being treated

The usual dose is

• Ovarian cancer and small cell lung cancer: 1.5 mg per square meter of body surface area per day. You will receive treatment once a day for 5 days. This treatment schedule will normally be repeated every 3 weeks.
• Cancer of the cervix: 0.75 mg per square meter of body surface area per day. You will receive treatment once a day for 3 days. This treatment schedule will normally be repeated every 3 weeks.

When treating cancer of the cervix, Topotecan Accord is given in combination with another medicine called cisplatin. Your doctor will determine the correct dose of cisplatin for you.

How Topotecan Accord is given

A doctor or nurse will give you Topotecan Accord through a vein in your arm over about 30 minutes.

Treatment may vary depending on the results of regular blood tests.

4. Possible side effects

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

Serious side effects: tell your doctor

These very commonside effects may affect more than 1 in 10 peopletreated with topotecan:

• Signs of infection:Topotecan Accord may reduce the number of white blood cells and decrease your resistance to infection. This can be life-threatening. Signs include:
• • fever
  • severe deterioration of your general condition
  • local symptoms such as sore throat or urinary problems (e.g. burning sensation when urinating, which may be a urinary tract infection)

• Occasionally, severe stomach pain, fever, and possibly diarrhea (rarely with blood) may indicate intestinal inflammation (colitis).

These rareside effects may affect up to 1 in 1,000 peopletreated with topotecan:

• Severe allergic or anaphylactic reactions that cause swelling of the lips, face, or throat and lead to severe breathing difficulties, skin rash, or hives, anaphylactic shock (a severe drop in blood pressure, paleness, agitation, weak pulse, decreased level of consciousness).
• Lung inflammation (interstitial lung disease):you are more at risk if you have existing lung disease, have received radiotherapy to the lungs, or have taken medicines that can cause lung damage. Signs include:
• • difficulty breathing
  • cough
  • fever

Tell your doctor immediatelyif you notice any of these symptoms, as you may need to be hospitalized.

Very common side effects

May affect more than 1 in 10 peopletreated with topotecan:

• Feeling of general weakness and tiredness (temporary anemia). In some cases, you may need a blood transfusion.
• Abnormal decrease in the number of white blood cells (neutropenia), which may be accompanied by fever and signs of infection (febrile neutropenia).
• Bruising or unusual bleeding, caused by a decrease in the blood clotting cells. This can lead to heavy bleeding from relatively small wounds, such as a small cut. Rarely, it can cause more severe bleeding. Talk to your doctor for advice on how to minimize the risk of bleeding.
• Weight loss and loss of appetite (anorexia), tiredness, weakness.
• Nausea, vomiting, diarrhea, stomach pain, constipation.
• Inflammation and ulcers in the mouth, tongue, or gums.
• High body temperature (fever).
• Hair loss.

Common side effects

May affect up to 1 in 10 peopletreated with topotecan:

• Allergic or hypersensitivity reactions (including skin rash)
• Yellowing of the skin
• Feeling of itching
• Feeling of discomfort
• Deficiency of all three cellular components (red blood cells, white blood cells, and platelets) of the blood (pancytopenia).

Rare side effects

May affect up to 1 in 1,000 peopletreated with topotecan:

• Severe allergic or anaphylactic reactions.
• Swelling caused by fluid accumulation (angioedema)
• Mild pain and inflammation at the injection site
• Itchy skin rash (or hives)

Very rare side effects

May affect up to 1 in 10,000 peopletreated with topotecan:

• Blood leakage into tissues (extravasation)

Side effects of unknown frequency

The frequency of some side effects cannot be estimated from the available data (effects from spontaneous reports and frequency cannot be estimated):

• Severe stomach pain, nausea, vomiting with blood, black or bloody stools (possible symptoms of gastrointestinal perforation).
• Sores in the mouth
• Difficulty swallowing
• Abdominal pain
• Nausea
• Vomiting
• Diarrhea
• Bloody stools (possible signs and symptoms of inflammation of the lining of the mouth, stomach, and/or intestines [mucosal inflammation]).

If you are being treated for cancer of the cervix, you may experience side effects related to the other medicine (cisplatin) that you will receive with Topotecan Accord. These side effects are described in the package leaflet for cisplatin.

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 to the Spanish Medicines Agency (AEMPS) at www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Topotecan Accord

• Keep out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
• Store below 25°C.
• Keep the vial in the outer carton to protect it from light.
• This medicine is for single use only. It must be diluted immediately after opening.
• Physical and chemical stability of the diluted solution has been demonstrated for 30 days at 25°C under normal lighting conditions and at 2-8°C when protected from light. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Topotecan Accord contains

• The active substance is topotecan hydrochloride. Each 1 ml vial contains 1 mg of topotecan (as hydrochloride). Each 4 ml vial contains 4 mg of topotecan (as hydrochloride).
• The other ingredients are: tartaric acid (E334), water for injections, hydrochloric acid (E507), and sodium hydroxide (for pH adjustment).

Appearance and pack contents

This medicine is a concentrate for solution for infusion.

The concentrate is a clear yellow solution. It is packaged in a glass vial sealed with a fluorotec rubber stopper and a removable aluminum seal.

Each 1 ml vial contains 1 mg of topotecan (as hydrochloride).

Each 4 ml vial contains 4 mg of topotecan (as hydrochloride).

This medicine is available in packs containing 1 vial or 5 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice,

Poland

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens, Lamia, Schimatari, 32009,

Greece

This medicine is authorised in the Member States of the European Economic Area under the following names

Date of last revision of this leaflet:May 2023.

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals

Instructions on how to prepare, store, and dispose of Topotecan Accord

Instructions for dilution

The concentrate is a clear yellow solution containing 1 mg per ml of Topotecan. It requires dilution with the appropriate volume of sodium chloride 9 mg/ml (0.9%) injection solution or glucose 50 mg/ml (5%) injection solution to achieve a final concentration of Topotecan between 25 and 50 micrograms/ml in the infusion solution.

Storage of the prepared solution

Physical and chemical stability of the diluted solution has been demonstrated for 30 days at 25°C under normal lighting conditions and at 2-8°C when protected from light. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Handling and disposal

Usual procedures for handling and disposing of antineoplastic medicines should be followed:

• staff should be trained to dilute the medicine.
• healthcare staff should not handle this medicine during pregnancy.
• healthcare staff handling this medicine during dilution should wear protective clothing, including a mask, glasses, and gloves.
• all materials used for administration or cleaning, including gloves, should be placed in high-risk waste disposal bags for incineration at high temperature.

Accidental contact with skin or eyes should be treated immediately with plenty of water.