Potactasol 1 mg powder for concentrate for solution forinfusion

Potactasol helps to kill tumour cells.

Potactasol is used to treat:

• ovarian cancer or small cell lung cancer that has come back after chemotherapy
• advanced cervical cancer if surgery or radiotherapy is not possible. In this case Potactasol treatment is combined with medicines containing cisplatin.

Do not use Potactasol

• if you are allergic (hypersensitive) to topotecan or any of the other ingredients of Potactasol (listed in section 6 under ?What Potactasol contains?);
• if you are breast-feeding. You should stop breast-feeding before starting treatment with Potactasol;
• if your blood cell counts are too low. Tell you doctor if you think any of these could apply to you.

Take special care with Potactasol

Tell your doctor:

• if you have any kidney problems. Your dose of Potactasol may need to be adjusted. Potactasol is not recommended in case of severe kidney impairment;
• if you have liver problems. Potactasol is not recommended in case of severe liver impairment;
• if you suffer from lung inflammation with signs such as cough, fever and difficulties in breathing, see also section 4 ?Possible side effects?.

Potactasol may cause a decrease in the number of blood clotting cells (platelets). This can lead to severe bleeding from relatively small injuries such as a small cut. Rarely, it can lead to more severe bleeding (haemorrhage). Talk to your doctor for advice on how to minimize the risk of bleeding.

The incidence of side effects is more frequent in patients who are in poor general health. The doctor will evaluate your general health during the treatment and you should tell him/her in case you have fever, infection or are in some ways feeling unwell.

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Potactasol should not be used in pregnant women, unless clearly necessary. If you are or think you might be pregnant, tell your doctor immediately.

Women of child-bearing potential should use effective contraception to avoid becoming pregnant while on treatment.

Male patients, who may wish to father a child, should ask their doctor for family planning advice or treatment.

You must not breast-feed while on treatment with Potactasol.

Driving and using machines

Potactasol can make you feel tired or weak. If you experience this, do not drive or use machines.

Important information about some of the ingredients of Potactasol

This medicine contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ?sodium-free?.

Your dose of Potactasol will depend on:

• the disease being treated, - your body surface area (m 2),
• the results of blood tests carried out before and during treatment,
• how well you tolerate treatment.

Adults
Ovarian cancer and small cell lung cancer

The usual dose is 1.5 mg per m 2 of body surface area once daily for 5 days. This treatment cycle will normally be repeated every three weeks.

Cervical cancer

The usual dose is 0.75 mg per m 2 of body surface area once daily for 3 days. This treatment cycle will normally be repeated every three weeks.
For cervical cancer, it will be used together with another anticancer medicines containing cisplatin. For more information about cisplatin, please refer to the corresponding package leaflet.

Children
The experience in children is limited and treatment is therefore not recommended.

How Potactasol is prepared

Topotecan is supplied as a powder for concentrate for solution for infusion. The powder must be dissolved, and the resulting concentrate further diluted before administration.

How Potactasol is given

A doctor or nurse will give you the reconstituted and diluted Potactasol solution as an infusion (drip), usually into your arm, over about 30 minutes.

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

These side effects may occur with certain frequencies, which are defined as follows:

• 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

You must tell your doctor immediately if you experience any of the following serious side effects. They may require hospitalisation and could even be life-threatening.

• Infections (very common), with signs such as:
• fever
• serious decline of your general condition
• local symptoms, such as sore throat or burning sensation when urinating
• severe stomach pain, fever and possibly diarrhoea (rarely with blood) can be signs of bowel inflammation (neutropenic colitis) Potactasol may reduce your ability to fight infections.
• Lung inflammation (rare),with signs such as:
• difficulty in breathing
• cough
• fever The risk of developing this severe condition (interstitial lung disease) is higher if you currently have lung problems, or if you have received previous radiation treatment or medicines that affected your lungs, see also section 2 ?Take special care with Potactasol?. This condition can be fatal.

Other side effects with Potactasol include:

Very common side effects

• Feeling generally weak and tired, which can be symptoms of a decrease in the number of red blood cells (anaemia). In some cases you may need a blood transfusion.
• Decrese in number of circulating white blood cells (leucotyes) in the blood. Abnormal low number of neutrophil granulocytes (a type of white blood cell) in the blood, with or without fever.
• Unusual bruising or bleeding, sometimes severe, caused by a decrease in the number of blood clotting cells (platelets).
• Weight loss and loss of appetite (anorexia); tiredness; weakness.
• Feeling sick (nausea), vomiting; diarrhoea; stomach pain; constipation.
• Inflammation of the lining of the mouth and digestive tract.
• Fever.
• Infections.
• Hair loss.

Common side effects

• Allergic (hypersensitivity) reactions (including rash).
• Abnormal high level of bilirubin, a waste product produced by the liver during breakdown of red blood cells. Symptoms may include yellow skin (jaundice).
• Decrease in the number of all blood cells (pancytopenia).
• Feeling unwell.
• Serious blood infection, which can be fatal.
• Itching (pruritus).

Rare side effects

• Severe allergic (anaphylactic) reactions.
• Swelling caused by fluid build-up (angioedema) e.g. around the eyes and lips as well as hands, feet and throat. If severe it may cause breathing difficulties.
• Itchy rash (or hives).

Very rare side effects

• Mild pain and inflammation at the site of injection due to accidental administration of the medicinal product into the surrounding tissue (extravasation) e.g. by leakage.

If you are being treated for cervical cancer, you may get side effects from the other medicine (cisplatin) that you will be given along with Potactasol.

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

Keep out of the reach and sight of children.

Do not use Potactasol after the expiry date which is stated on the vial and carton.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Potactasol contains

• The active substance is topotecan. Each vial contains 1 mg (with 10 % overage of fill) or 4 mg topotecan (as hydrochloride). After reconstitution 1 ml concentrate contains 1 mg topotecan.
• The other ingredients are: mannitol (E421), tartaric acid (E334), hydrochloric acid (E507) and sodium hydroxide.

What Potactasol looks like and contents of the pack

Potactasol is supplied in type I colourless glass vials with grey bromobutylic stopper and aluminium seals with plastic flip-off caps.

Packs:

1 vial containing 1 mg topotecan
1 vial containing 4 mg topotecan

Marketing Authorisation Holder

Actavis Group PTC ehf.Reykjavíkurvegi 76-78
Hafnarfjörður

Iceland

Manufacturer

S.C. Sindan-Pharma S.R.L.
11 Ion Mihalache Blvd
Bucharest
Romania

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

BelgiëBelgiqueBelgien ALL-in-1 bvba TélTel 32 032 86 88 88 LuxembourgLuxemburg ALL-in-1 bvba BelgiqueBelgien TélTel 32 032 86 88 88

Te. 359 2 9321 680 Magyarország Actavis Hungary Kft Tel. 36 1 501 7001

eská republika Actavis CZ a.s. Tel 420251001680 Malta Actavis Ltd. Tel 35621693533

Danmark Actavis AS Tlf 45 72 22 30 00 Nederland Actavis B.V. Tel 035 -54 299 33

Deutschland Actavis Deutschland GmbH Co. KG Telefon 49 021731674 0 Norge Actavis Norway AS Tlf 47 815 22 099

Eesti UAB Actavis Baltics Eesti Filiaal Tel 372 6100 565 Österreich Actavis GmbH Tel 43 0662 435 235 00

Polska Actavis Polska Sp. z o.o. Tel. 48 22 512 29 00 PharOS - Pharmaceutical Oriented Services Ltd Tel 30 210 66 64 667 8

España Actavis Spain, S.A. Tfno. 34 91 630 86 45 Portugal Actavis AS Sucursal Tel 351 21 722 06 50

France Actavis Tél 33 1 40 83 77 77 România Actavis SRL Tel 40 21 318 17 77

Slovenija Sanolabor d.d. phone 386 01 585-4211 Ireland Actavis UK Limited United Kingdom Tel 441271311200

Ísland Slovenská republika

Actavis Group PTC ehf Sími 354-550 3300 Actavis s.r.o. Tel 421 2 3255 3801

Italia Actavis Italy S.p.A. Tel 39 0331 583111 SuomiFinland Actavis Oy PuhTel 358 09 348 233

A. Potamitis Medicare Ltd 35722313611 Sverige Actavis AB Tel 46 8 13 63 70

Latvija Actavis Baltics prstvniecba Latvij Tel 371 67067873 United Kingdom Actavis UK Limited Tel 441271311200

Lietuva
UAB ?Actavis Baltics?
Tel: +370 5 260 9615

This leaflet was last approved in {MM/YYYY}.

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The following information is intended for medical or healthcare professionals only:

Potactasol

INSTRUCTIONS ON USE

Guidelines for the safe handling and disposal of antineoplastic agents

1. Reconstitution and dilution of the medicinal product must be performed by trained personnel.

2. The preparation should be performed in a designated area under aseptic conditions.

3. Adequate protective disposable gloves, goggles, gown and mask should be worn.

4. Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. In the event of contact with the eyes, irrigate with large amounts of water. Then seek medical evaluation by a physician.

5. In case of skin contact, thoroughly wash the affected area with large amount of water. Always wash hands after removing gloves.

6. Pregnant staff should not handle the cytotoxic preparation.

7. Adequate care and precautions should be taken in the disposal of items (syringes, needles etc) used to reconstitute and/or dilute cytotoxic medicinal products. Any unused product or waste material should be disposed of in accordance with local requirements.

Reconstitution and dilution prior to administration

Before infusion, Potactasol powder for concentrate for solution for infusion must be reconstituted with an appropriate volume of water for injections, as follows:

• Potactasol 1 mg with 1.1 ml water for injections (as it contains 10 % overage of fill)
• Potactasol 4 mg with 4 ml water for injections

Reconstitution will result in a concentrate containing 1 mg topotecan per ml.
This concentrate (1 mg/ml) must be diluted prior to administration.

The volume of reconstituted concentrate corresponding to the calculated individual dose, should be further diluted with either sodium chloride 9 mg/ml (0.9 %) solution for injection or 50 mg/ml (5 %) glucose solution for infusion, to a final concentration of between
25 and 50 microgram per ml in the solution for infusion, for example:

Volume for 25 microgramml solution Volume for 50 microgramml solution 1 ml of 1 mgml topotecan solution Add 39 ml to give 40 ml Add 19 ml to give 20 ml 4 ml of 1 mgml topotecan solution Add 156 ml to give 160 ml Add 76 ml to give 80 ml

Storage after reconstitution and dilution
Chemical and physical stability of the concentrate has been demonstrated for 24 hours at 25 ± 2°C, in normal light conditions and 24 hours at 2 to 8°C, protected from light.

Chemical and physical stability of the solution obtained after dilution of the concentrate in sodium chloride 9 mg/ml (0.9 %) solution for injection or 50 mg/ml (5 %) glucose solution for infusion has been demonstrated for 4 hours at 25 ± 2°C, in normal lighting conditions .The concentrates tested were reconstituted and stored at 25 ± 2°C for 12 hours and 24 hours respectively after reconstitution, and then diluted.

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.

Disposal
Any unused product or waste material should be disposed of in accordance with local requirements. All items for administration or cleaning, 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.