Topotecan Hospira 4 mg/4 ml concentrate for solution forinfusion

Topotecan Hospira is an anti-cancer medicine, which will be given to you through a drip, as an infusion into a vein.

Topotecan Hospira is used to treat:

• small cell lung cancer that has come back after chemotherapy
• advanced cervical cancer if surgery or radiotherapy treatment is not possible. When treatingcervical cancer, Topotecan Hospira is combined with another drug called cisplatin.

Your doctor will decide with you whether Topotecan Hospira therapy is better than further treatment with your initial chemotherapy.

You should not receive Topotecan Hospira:

• if you are allergic (hypersensitive ) to topotecan or any of the other ingredients of Topotecan Hospira
• if you are breast-feeding
• if your blood cell counts are too low. Your doctor will tell if this applies to you based on the resultsof your last blood test.

If you think any of these things may apply to you, please tell your doctor.

Take special care with Topotecan Hospira

Your doctor needs to know before you are given this medicine if:

• you have a problem with your kidneys
• you have a problem with your liverIf either of these applies to you, your doctor will need to know before treatment begins, as he or she may need to adjust your dose
• you are pregnant or plan to become pregnant
• you plan to father a childIf either of these applies to you, your doctor will need to know before treatment begins, as topotecan may harm a baby which is conceived before, during or soon after treatment. You should therefore use an effective method of contraception. Ask your doctor for further advice.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal medicines. It is also important that you check with your doctor before you start taking any other medicines or herbal products while you are treated with Topotecan Hospira .

Using Topotecan Hospira with food and drink

Alcohol: There is no known interaction between topotecan and alcohol; however, you should check with your doctor whether drinking alcohol is advisable for you.

Pregnancy and breast-feeding

Topotecan is not recommended for use by pregnant women . Topotecan may harm a baby which is conceived before, during or soon after treatment. You should tell your doctor if you are pregnant before your treatment starts.

An effective method of contraception should be used during treatment, to avoid becoming pregnant or fathering a child. Do not try to become pregnant or father a child until a doctor advises you that it is safe to do so. You can ask your doctor for family planning advice. If a baby is conceived/you fall pregnant during treatment, you should tell their doctor immediately.

Do not breast-feed if you are being treated with topotecan. Do not restart breastfeeding until the doctor tells you it is safe to do so.

Driving and using machines

Topotecan can make you feel tired. If you feel tired or weak, do not drive and do not use machines.

The dose of topotecan you receive is calculated by your doctor, based on:
? your body size (your surface area, measured in square metres (m 2))

• the results of your blood tests (these will be carried out before your treatment starts)
• the disease you are being treated for

The usual dose

Your doctor will calculate what dose you need to be given, based on your own circumstances. Typical doses are given below.

? For small cell lung cancer: 1.5 milligrams per m 2 of body surface area per day.
? For cervical cancer: 0.75 milligrams per m 2 of body surface area per day. When treating cervical cancer, topotecan will be given to you with another medicine, called cisplatin. Your doctor will advise you about the correct dose of cisplatin.

How topotecan is given

Topotecan Hospira is a concentrated solution which will be diluted before use. A doctor or nurse will give you your dose of topotecan as an infusion (a drip). It is usually given into a vein in your arm, over a period of about 30 minutes.

Duration of treatment

Your treatment may vary and will depend on the results of your regular blood tests. Typical courses of treatment are given below.

• For small cell lung cancer: treatment will usually be given once a day for 5 days.
• For cervical cancer: treatment will usually be given once a day for 3 days.

This course of treatment will normally be repeated every three weeks, for all types of cancer. Your doctor will decide when to stop your treatment.

If you are concerned about your dose or the duration of your treatment, talk to your doctor.

Like all medicines, Topotecan Hospira can cause side effects, although not everybody gets them.

The frequency of possible side effects listed below is defined using the following convention:

Very common affects more than 1 user in 10 Common affects 1 to 10 users in 100 Uncommon affects 1 to 10 users in 1,000 Rare affects 1 to 10 users in 10,000 Very rare affects less than 1 user in 10,000 Not known frequency cannot be estimated from the available data

Serious side effects: tell your doctor

The following very common side effects may be serious. Tell your doctor immediately if you notice any of these symptoms, as hospitalisation may be necessary.

• Signs of infection. Topotecan may reduce the number of white blood cells in your body and make you more likely to get an infection. This can be life threatening. A blood test will be taken to check for a reduction in the amount of your white blood cells. Signs of infection should be monitored and include: - fever - serious deterioration in your general condition/health - local symptoms, such as a sore throat or urinary problems (for example, a burning sensation when urinating, which may be a sign of a urinary tract infection)
• Severe stomach pain, fever and possibly diarrhoea (rarely with blood).Occasionally, these symptoms can be a sign of bowel inflammation ( colitis)

The following rare side effects may be serious. Tell your doctor immediately if you notice any of the symptoms.

• Lung inflammation (interstitial lung disease). You are most at risk of this side effect if you havean existing lung disease, if you have had radiation treatment on your lungs, or have previously taken medicines that caused lung damage. Signs of lung inflammation include: - difficulty in breathing - cough - fever Very common side effects

The following side effects are very common. Tell a doctor if any of these become troublesome.

• Feeling generally weak and tired (temporary anaemia). In some cases you may need a bloodtransfusion
• Unusual bruising or bleeding, caused by a decrease in the number of clotting cells in the blood. Thiscan lead to severe bleeding from relatively minor injuries such as a small cut. Rarely, it can lead to more severe bleeding ( haemorrhage). Talk to your doctor for advice on how to minimise the risk of bleeding
• Weight loss and loss of appetite ( anorexia), tiredness, weakness, feeling unwell
• Feeling sick (nausea), being sick ( vomiting), diarrhoea, stomach pain, constipation
• Inflammation and ulcers of the mouth, tongue, or gums
• High body temperature ( fever)
• Hair loss

Common side effects

The following side effects are common. Tell a doctor if any of these become troublesome.

• Allergic or hypersensitivity reactions (including rash)
• Yellow skin (jaundice)
• Itching sensation
• Muscle pain

Rare side effects

The following side effects are rare. Tell a doctor if any of these become troublesome.

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

Note for patients treated for cervical cancer: If you are being treated for cervical cancer, you will usually receive another medicine called cisplatin, alongside your topotecan treatment. You may also get side effects from the cisplatin medication. These side effects will be described in the cisplatin patient information leaflet.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your doctor.

Keep out of the reach and sight of children.

Do not use Topotecan Hospira after the expiry date stated on the vial and carton after EXP.

Store in a refrigerator (2°C-8°C). Do not freeze.

Keep the vial in the outer carton to protect from light.

This medicine is for single use only. After opening, the product should be used immediately. If not used immediately, Topotecan Hospira can be used for up to 24 hours when stored in the fridge (protected from light) or at room temperature (in normal daylight conditions).

Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic material.

What Topotecan Hospira contains

The active substance in Topotecan Hospira is topotecan (as hydrochloride). 1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride). Each 4 ml vial of concentrate contains 4 mg 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).

What Topotecan Hospira looks like and the contents of the pack

Topotecan Hospira is a clear, yellow or yellow-green concentrate for solution for infusion, supplied in clear glass vials, each containing 4 ml concentrate. Topotecan Hospira is available in two pack sizes, containing either 1 vial or 5 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Hospira UK Limited
Queensway
Royal Leamington Spa
Warwickshire
CV31 3RW
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

AT DE Hospira Deutschland GmbH Tel 49 0 89 43 77 77 0 BE LX NL Hospira Benelux BVBA TélTel 32 2 332 03 15

CZ EE EL IE LT LV MT PL RO SI SK UK Hospira UK Limited Tel 44 0 1926 820820 CY Name N.Karoullas Pharmaceutical Trading Co Ltd 33, Artemidos avenue, 6025 Larnaca Tel 24656165 Mob. 99403969 Email n.karoullasptc-ltd.com

DK FI IS NO SE Hospira Nordic AB Tel 46 0 8 672 85 00 ES Hospira Productos Farmacéuticos y Hospitalarios S.L. Tel 34 914847100

FR Hospira France Tél 33 0 826 30 03 02 HU Pharmacenter Hungary Ltd Tel. 36-1-209-5927

IT Hospira Italia Srl Tel 39 0812405912 PT Hospira Portugal Lda Tel 351 214857434

This leaflet was last approved in

The following information is intended for medical or health care professionals only.

Storage, Use, Handling & Disposal of Topotecan Hospira

Storage

Unopened vial: Store in a refrigerator (2°C-8°C). Do not freeze. Keep the vial in the outer carton in order to protect from light.

Use

Refer to the SPC for full details.

Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion requires dilution to a final concentration of 25-50 micrograms/ml, prior to administration to the patient. The approved diluents for the concentrate are sodium chloride 9 mg/ml (0.9%) solution for injection and glucose 50 mg/ml (5%) solution for injection. Use the aseptic technique during any further dilution of the solution for infusion.

Parenteral products should be visually inspected for particulate matter and discolouration prior to administration. Topotecan Hospira is a yellow/yellow green solution. If visible particles areobserved, the product should not be administered.

Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count

of ?1.5 x 10 9/l, a platelet count of ? 100 x 10 9/l and a haemoglobin level of ? 9g/dl (after transfusion if necessary). Neutropenia and thrombocytopenia should be managed. For further details, refer to the SPC.

Dosage: Small Cell Lung Carcinoma

Initial dose: 1.5 mg/ m 2 body surface area/day, administered by intravenous infusion over 30 minutes for 5 consecutive days, with a 3 week interval between the start of each course.

Subsequent doses: Topotecan should not be re-administered unless the neutrophil count is ? 1 x 109/l, the platelet count is ? 100 x 10 9/l, and the haemoglobin level is ? 9 g/dl (after transfusion if necessary).

Dosage: Cervical Carcinoma

Initial dose: 0.75 mg/m 2/day administered as 30 minute intravenous infusion daily, on days 1, 2 and 3. Cisplatin is administered as an intravenous infusion on day 1 at a dose of 50 mg/m 2/day and following the topotecan dose. This treatment schedule is repeated every 21 days for 6 courses or until progressive disease.

Subsequent doses: Topotecan should not be re-administered unless the neutrophil count is more than or equal to 1.5 x 10 9/l, the platelet count is more than or equal to 100 x 10 9/l, and the haemoglobin level is more than or equal to 9g/dl (after transfusion if necessary).

Dosage: Renally impaired patients

Limited data indicate that the dose should be reduced in patients with moderate renal impairment. Please refer to the SPC for further details.

Dosage: Paediatric population

Limited data available. Use not recommended.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C under normal light 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 prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Handling and disposal
The normal procedures for proper handling and disposal of anti-tumour medicinal products should be adopted:

• Staff should be adequately trained in the preparation, administration and disposal of cytotoxics
• Pregnant staff should be excluded from working with this medicinal product.
• Staff handling this medicinal product should wear adequate protective clothing including mask,goggles and gloves.
• All items for used in the preparation, administration, and cleaning of the medicinal product, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration. Liquid waste may be flushed with large amounts of water.
• Accidental contact with the skin or eyes should be treated immediately with copious amounts of water. If there is lasting irritation, a doctor should be consulted.
• Any unused product or waste material should be disposed of in accordance with local requirements.