Topotecan Hospira

Package leaflet: Information for the user

Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion

topotecan
Read this leaflet carefully before using 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.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

1. What Topotecan Hospira is and what it is used for
2. What you need to know before using Topotecan Hospira
3. How Topotecan Hospira is used
4. Possible side effects
5. How to store Topotecan Hospira
6. Contents of the pack and other information

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

Topotecan Hospira helps to treat cancers. A doctor or nurse will administer the medicine to you in hospital by intravenous infusion.
Topotecan Hospira is used to treat:

• ovarian cancer or small cell lung cancer that has relapsed after chemotherapy
• advanced cervical cancer when surgical or radiotherapy treatment is not possible. In the treatment of cervical cancer, Topotecan Hospira is given in combination with another medicine called cisplatin.

Your doctor will determine whether treatment with Topotecan Hospira is preferable to further initial chemotherapy.

2. What you need to know before using Topotecan Hospira

Do not use Topotecan Hospira:

• • if you are allergic to topotecan or to any of the other ingredients of this medicine (listed in section 6).
• • if you are breastfeeding.
• • if your blood cell count is too low. Depending on your blood test results, your doctor will determine whether this applies to you.

Tell your doctor if any of the above apply to you.
Warnings and precautions
Before you are given this medicine, your doctor must know:

• if you have any kidney or liver problems. Your dose of Topotecan Hospira may need to be adjusted.
• if you are pregnant or think you might become pregnant. See section below “Pregnancy and breastfeeding”.
• if you intend to become a father. See section below “Pregnancy and breastfeeding”.

If any of the above apply to you, tell your doctor.
Other medicines and Topotecan Hospira
Tell your doctor if you are taking, have recently taken, or might take any other
medicines, including herbal products or medicines obtained without a prescription.
Remember to inform your doctor if you start taking any other medicines while being treated
with Topotecan Hospira.
Pregnancy and breastfeeding
Topotecan is not recommended for use in pregnant women. It may harm a child conceived
before, during, or immediately after treatment. You must always use effective contraception during
treatment with topotecan and for 6 months after completion of treatment. Ask your doctor for advice.
Do not attempt to become pregnant until your doctor tells you it is safe to do so.
Men are advised to use effective contraception and to avoid fathering a child during
treatment with topotecan and for 3 months after completion of treatment. Male patients who
wish to father children should consult their doctor for advice or treatment regarding family planning.
If your partner becomes pregnant during your treatment, you must inform your doctor immediately.
Do not breastfeed during treatment with topotecan. Do not resume breastfeeding until
your doctor tells you it is safe to do so.
Driving and using machines
Topotecan may cause tiredness. If you feel tired or weak, do not drive or operate machinery.
Topotecan Hospira contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.
If your doctor uses a saline solution to dilute Topotecan Hospira, the amount of sodium you receive may be higher.

3. How to use Topotecan Hospira

The dose of topotecan you will be given is calculated by your doctor based on:

• body surface area (body surface area, measured in square meters)
• results of blood tests (which will be performed before treatment)
• the disease being treated.

The usual dose

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

In the treatment of cervical cancer, Topotecan Hospira is used in combination with another medicine called cisplatin. Your doctor will determine the correct dose of cisplatin for you.
Treatment may be adjusted depending on the results of regular blood tests.

How topotecan is administered
Your doctor or nurse will administer the dose of topotecan by infusion into your arm over approximately 30 minutes.

4. Possible side effects

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

Serious side effects: tell your doctor

These side effects are very common and may occur in more than 1 in 10 people treated with Topoetecan Hospira:

• Signs of infection. Topotecan can reduce the number of white blood cells and lower resistance to infections. This could even be life-threatening. Such signs include:
  • fever
  • severe worsening of general condition
  • local symptoms, such as sore throat or urinary problems (for example, a burning sensation when urinating, which may be caused by a urinary tract infection)
• Occasionally, severe stomach pain, fever, and possibly diarrhoea (rarely with blood) may be signs of inflammation of the intestine (colitis).

This side effect is rare and may occur in up to 1 in 1,000 people treated with Topotecan Hospira:

• Inflammation of the lungs (interstitial lung disease). If you already have lung diseases, have undergone radiotherapy to the lungs, or have taken medicines causing lung damage, you are at higher risk. Signs of lung inflammation include:
  • difficulty breathing
  • cough
  • fever

If you experience any symptoms related to these conditions, speak immediately with your doctor, as hospitalisation may be necessary.

Very common side effects

These side effects may occur in more than 1 in 10 people treated with Topotecan Hospira:

• General feeling of weakness and tiredness (temporary anaemia). In some cases, a blood transfusion may be required.
• Unusual bruising and bleeding, caused by a reduction in the number of cells responsible for blood clotting.

This may lead to serious bleeding following relatively minor injuries, such as small cuts. Rarely, it may result in more severe bleeding (haemorrhage). Speak with your doctor for advice on how to reduce the risk of bleeding.

• Weight loss and loss of appetite (anorexia), tiredness, weakness
• Feeling unwell (nausea), being sick (vomiting), diarrhoea, stomach pain, constipation
• Inflammation and ulcers in the mouth, tongue or gums
• High body temperature (fever)
• Hair loss

Common side effects

These may occur in up to 1 in 10 people treated with Topotecan Hospira:

• Allergic or hypersensitivity reaction (including rash)
• Yellowing of the skin
• Feeling unwell
• Itching

Rare side effects

These may occur in up to 1 in 1,000 people treated with Topotecan Hospira:

• Severe allergic or anaphylactic reaction
• Swelling due to fluid accumulation (angioedema)
• Mild pain and inflammation at the injection site
• Itchy skin rash (or urticaria)

Side effects with unknown frequency

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

• Severe stomach pain, nausea, blood in vomit, dark or bloody stools (possible symptoms of gastrointestinal perforation).
• Mouth sores, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhoea, bloody stools (possible signs and symptoms of inflammation of the inner lining of the mouth, stomach and/or intestine [mucositis]).

If you are being treated for cervical cancer: you may experience side effects due to the other medicine (cisplatin) you are receiving together with Topotecan Hospira. These side effects are described in the patient leaflet for cisplatin.

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Topotecan Hospira

Keep this medicine out of the sight and reach of children.
Do not use Topotecan Hospira after the expiry date stated on the vial and on the outer packaging after the word "Exp".
Store in a refrigerator (2°C–8°C). Do not freeze.
Keep the vial in the outer packaging to protect it from light.
This medicine is for single use only. After first opening, the product should be used immediately. If not used immediately, Topotecan Hospira may be used within 24 hours when stored refrigerated (protected from light) or at room temperature (under normal lighting conditions).
Do not administer the medicine if visible particles are present in the solution.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Topotecan Hospira Contains
The active substance in Topotecan Hospira is topotecan (as hydrochloride). 1 ml of concentrate for
infusion solution contains 1 mg of topotecan (as hydrochloride). Each 4 ml vial of concentrate contains 4 mg of topotecan (as hydrochloride).
The other ingredients are: tartaric acid (E334), water for injections, and hydrochloric acid (E507) or sodium hydroxide (to adjust the pH of the solution).

Description of the Appearance of Topotecan Hospira and Package Contents
Topotecan Hospira is a clear, yellow or yellow-green concentrate for infusion solution, supplied in transparent glass vials, each containing 4 ml of concentrate. Topotecan Hospira is available in two presentations: packages containing either 1 vial or 5 vials.
Not all pack sizes may be marketed.

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

Manufacturer
Pfizer Service Company BV
Hermeslaan 11
1932 Zaventem
Belgium

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

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel. +370 5 251 4000
Tél/Tel: +32 (0)2 554 62 11

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

Česká republika Malta
Pfizer, spol. s r.o. Drugsales Ltd
Tel: +420 283 004 111 Tel: +356 21419070/1/2

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

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

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 6785800 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.
Tél: +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 Unlimited Company Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh/Tel: +358 (0)9 430 040

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

Κύπρος
Pfizer Ελλάς Α.Ε. (Cyprus Branch)
Τηλ.: +357 22817690

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

This Patient Information Leaflet was last approved on

Other Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

The following information is intended for use by physicians or healthcare professionals only.

Storage, Use, Handling, and Disposal of Topotecan Hospira

Storage
Intact vial: Store in a refrigerator (2°C–8°C). Do not freeze. Keep the vial in its outer packaging to protect the medicinal product from light.

Use
For further details, refer to the Summary of Product Characteristics (SmPC).
Topotecan Hospira 4 mg/4 ml concentrate for infusion solution must be diluted before administration to the patient to a final concentration of 25–50 micrograms/ml. The approved diluents for the concentrate are 9 mg/ml (0.9%) sodium chloride injection solution and 50 mg/ml (5%) glucose injection solution. Aseptic techniques must be used during further dilution of the infusion solution.

Parenteral products should be inspected visually for particulate matter or discoloration prior to use. Topotecan Hospira is a yellow to yellow-green solution.

Prior to the first cycle of topotecan administration, the patient’s baseline neutrophil count must be ≥1.5 x 10⁹/l, platelet count ≥100 x 10⁹/l, and hemoglobin level ≥9 g/dl (after transfusion if necessary). Neutropenia and thrombocytopenia must be corrected; for further details, refer to the SmPC.

Dosage: Ovarian Cancer and Small Cell Lung Cancer
Initial dose: 1.5 mg/m² body surface area/day, administered as a 30-minute intravenous infusion for 5 consecutive days, with a 3-week interval between the start of each cycle.
Subsequent doses: Topotecan must not be administered unless the neutrophil count is ≥1 x 10⁹/l, platelet count ≥100 x 10⁹/l, and hemoglobin level ≥9 g/dl (after transfusion if necessary).

Dosage: Cervical Cancer
Initial dose: 0.75 mg/m²/day administered as a daily 30-minute intravenous infusion on days 1, 2, and 3. Cisplatin is administered as an intravenous infusion on day 1 at a dose of 50 mg/m²/day, after the topotecan dose. This treatment regimen is repeated every 21 days for 6 cycles or until disease progression.
Subsequent doses: Topotecan must not be administered unless the neutrophil count is ≥1.5 x 10⁹/l, platelet count ≥100 x 10⁹/l, and hemoglobin level ≥9 g/dl (after transfusion if necessary).

Dosage: Patients with Renal Impairment
Limited data suggest that the dose should be reduced in patients with moderate renal impairment. Refer to the SmPC for further details.

Dosage: Pediatric Population
Limited data are available. Use is not recommended.

The chemical and physical in-use stability has been demonstrated for 24 hours at 25°C under normal light conditions and at 2°C–8°C protected from light. From a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage conditions and duration prior to use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, provided reconstitution/dilution has been performed under controlled and validated aseptic conditions.

Handling and Disposal
Standard procedures for the safe handling and disposal of cytotoxic medicinal products must be followed.

• Personnel must be adequately trained in the preparation, administration, and disposal of cytotoxic agents.
• Pregnant personnel should be excluded from handling this medicinal product.
• Personnel handling this medicinal product must wear protective clothing, including masks, goggles, and gloves.
• All materials used in the preparation, administration, and cleaning of the medicinal product, including gloves, must be placed in high-risk waste disposal bags for incineration at high temperatures. Liquid waste may be dispersed with large amounts of water.
• Accidental contact with skin or eyes must be immediately rinsed with large amounts of water. If irritation persists, medical advice should be sought.
• Unused medicinal product or waste material must be disposed of in accordance with local regulations.