Potactasol

Package leaflet: Information for the user

Potactasol 1 mg powder for concentrate for solution for infusion, 4 mg powder for concentrate for solution for infusion

Topotecan
Please read this leaflet carefully before taking 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 or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Potactasol is and what it is used for

Potactasol contains the active substance topotecan, which helps kill cancer cells.
Potactasol is used to treat:

• ovarian cancer or small cell lung cancer that has relapsed after chemotherapy
• advanced cervical cancer when surgery or radiotherapy are not possible. In this case, treatment with Potactasol is combined with other medicines containing cisplatin.

2. What you need to know before using Potactasol

Do not use Potactasol

• 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 red blood cell count is too low. Your doctor will advise you if this applies, based on your most recent blood test results. Inform your doctor if any of these situations apply to you.

Warnings and precautions
Talk to your doctor before using Potactasol:

• if you have kidney problems. It may be necessary to adjust the dose of Potactasol. Use of Potactasol is not recommended in case of severe impairment of kidney function;
• if you have liver problems. Use of Potactasol is not recommended in case of severe impairment of liver function;
• if you have lung inflammation with symptoms such as cough, fever, and breathing difficulties; see also section 4 “Possible side effects”.

Potactasol may cause a reduction in the number of platelets, the blood cells responsible for blood clotting. This may lead to serious bleeding following relatively minor injuries, such as small cuts. Rarely, it may cause more severe bleeding (haemorrhage). Talk to your doctor for advice on how to minimize the risk of bleeding.
The incidence of side effects is higher in patients who are not in good general health. Your doctor will monitor your overall health condition during treatment. Inform your doctor immediately if you develop fever, infections, or any feeling of illness.
Use in children and adolescents
Experience in children and adolescents is limited; therefore, treatment is not recommended.
Other medicines and Potactasol
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Potactasol must not be used during pregnancy unless clearly necessary. Inform your doctor immediately if you are pregnant or suspect you may be pregnant.
You must always use effective contraception during treatment with Potactasol and for 6 months after completion of treatment. Ask your doctor for advice.
Men are advised to use effective contraception and to avoid fathering a child during treatment with Potactasol and for 3 months after completion of treatment.
Patients concerned about their fertility should seek medical advice on fertility and family planning options before starting treatment.
Do not breastfeed during treatment with Potactasol.
Driving and use of machines
Potactasol may cause tiredness or weakness. If you feel tired or weak, do not drive or operate machinery.
Potactasol contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore essentially “sodium-free”.

3. How to use Potactasol

The dose of Potactasol you are given will be calculated by your doctor based on:

• the disease to be treated,
• your body surface area (m²),
• the results of blood tests performed before and during treatment,
• how well you tolerate the treatment.

Adults
Ovarian carcinoma and small cell lung cancer
The usual dose is 1.5 mg per m² of body surface area once daily for 5 days.
This treatment cycle is normally repeated every three weeks.
Cervical cancer
The usual dose is 0.75 mg per m² of body surface area once daily for 3 days.
This treatment cycle is normally repeated every three weeks.
In the treatment of cervical cancer, topotecan is used in combination with other anticancer drugs containing cisplatin. Refer to the cisplatin package leaflet for further information.
Patients with reduced renal function
Your doctor may need to reduce the dose depending on kidney function.

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

How Potactasol is administered
A doctor or nurse will administer the reconstituted and diluted Potactasol solution to you as an intravenous infusion, drop by drop, into a vein, usually in the arm, over approximately 30 minutes.

If you are given too much Potactasol
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive too much Potactasol. In the unlikely event of an overdose, the doctor will monitor you for adverse effects. Inform the doctor or nurse if you have any concerns regarding the amount of medicine being administered to you.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
If you experience any of the following serious side effects, consult your doctor immediately.
Hospitalisation may be required and your life could even be at risk.

• Infections (very common; may affect more than 1 in 10 patients), with signs such as:
• Fever
• Severe deterioration in general condition
• Local symptoms, such as sore throat or a burning sensation when urinating
• Severe stomach pain, fever and possibly diarrhoea (rarely associated with blood) may be signs of intestinal inflammation (neutropenic colitis). Potactasol may reduce your ability to fight infections.
• Lung inflammation (rare; may affect up to 1 in 1,000 patients), with signs such as:
• Difficulty breathing
• Cough
• Fever. Your risk of developing this serious condition (interstitial lung disease) is higher if you already have lung disease, have previously undergone radiation therapy, or have previously taken medicines that caused lung damage; see also section 2 “Warnings and precautions”. This condition can be fatal.
• Severe allergic (anaphylactic) reactions (rare: may affect up to 1 in 1,000 patients), with symptoms such as:
• Swelling of the face, lips, tongue or throat, difficulty breathing, low blood pressure, dizziness and itchy rash.

Other side effects associated with the use of Potactasol are:
Very common side effects (may affect more than 1 in 10 patients)

• General feeling of weakness and fatigue, which may be symptoms of a reduced number of red blood cells (anaemia). In some cases, you may require a blood transfusion.
• Reduced number of circulating white blood cells (leucocytes). Abnormal reduction in the number of neutrophil granulocytes (a type of white blood cell) in the blood, with or without fever.
• Unusual bruising and bleeding, sometimes severe, caused by a decrease in the number of cells responsible for blood clotting (platelets).
• Weight loss and loss of appetite (anorexia); fatigue; weakness.
• Feeling unwell (nausea), vomiting; diarrhoea; stomach ache; constipation.
• Inflammation of the lining of the mouth and digestive tract.
• Fever.
• • Hair loss.

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

• Allergic reactions (hypersensitivity, including rash). Unusually high levels of bilirubin. Bilirubin is a “waste product” produced by the liver during the breakdown of red blood cells. Symptoms may include yellowing of the skin (jaundice).
• Decrease in the number of all blood cells (pancytopenia)
• Feeling unwell.
• Severe blood infection, which may be fatal.
• Itching.

Rare side effects (may affect up to 1 in 1,000 patients)

• Swelling due to fluid retention (angioedema), for example around the eyes and lips and in the hands, feet and throat. If these symptoms occur severely, they may cause breathing difficulties.
• Itchy skin rash (or urticaria).

Very rare side effects (may affect up to 1 in 10,000 patients)

• Mild pain and inflammation at the injection site following accidental administration of the medicine into surrounding tissues (extravasation), for example due to leakage of the medicine.

Not known (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 ulcers, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhoea, blood in 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) that you are receiving together with Potactasol.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Potactasol

Keep this medicine out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the vial and carton after EXP. The expiry date refers to the last day of that month.
Store the vial in the outer packaging to protect the medicine from light.

Storage after reconstitution and dilution
Chemical and physical stability of the concentrate has been demonstrated for 24 hours at a temperature of 25 ± 2°C under normal light conditions, and for 24 hours at 2°C to 8°C when protected from light.
Chemical and physical stability of the concentrated medicinal solution after dilution in infusion solution (0.9% sodium chloride and 5% glucose) has been demonstrated for 4 hours at room temperature under normal light conditions, using samples reconstituted and stored for 12 hours and 24 hours at 25 ± 2°C respectively, before dilution.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration of storage in use and the conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C, provided that reconstitution/dilution was carried out under validated and controlled aseptic conditions.
Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations governing cytotoxic materials.

6. Package contents and other information

What Potactasol contains

• The active substance is topotecan. Each vial contains 1 mg or 4 mg of topotecan (as hydrochloride). After reconstitution, 1 ml of concentrate contains 1 mg of topotecan.
• The other components are: mannitol (E421), tartaric acid (E334), hydrochloric acid (E507), and sodium hydroxide (see section 2).

Description of the appearance of Potactasol and contents of the pack
Potactasol is supplied in clear type I glass vials with grey bromobutyl rubber stoppers and aluminium seals with plastic flip-off caps. The vials may or may not be wrapped in a protective overwrap.
The vials contain either 1 mg or 4 mg of topotecan.
Each pack contains one vial.

Marketing Authorisation Holder
Actavis Group PTC ehf.
Dalshraun 1
220 Hafnarfjörður
Iceland

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

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

Belgium/Belgium/Belgium
Teva Pharma Belgium N.V./S.A./AG
Tél/Tel: +32 38207373

Lithuania
UAB Teva Baltics
Tel: +370 52660203

Bulgaria
Тева Фарма ЕАД
Tel: +359 24899585

Luxembourg/Luxembourg
Teva Pharma Belgium N.V./S.A./AG
Belgique/Belgien
Tél/Tel: +32 38207373

Czech Republic
Teva Pharmaceuticals CR, s.r.o.
Tel: +420 251007111

Hungary
Teva Gyógyszergyár Zrt.
Tel.: +36 12886400

Denmark
Teva Denmark A/S
Tlf.: +45 44985511

Malta
Teva Pharmaceuticals Ireland
Ireland
Tel: +44 2075407117

Germany
ratiopharm GmbH
Tel: +49 73140202

Netherlands
Teva Nederland B.V.
Tel: +31 8000228400

Estonia
UAB Teva Baltics Estonia branch
Tel: +372 6610801

Norway
Teva Norway AS
Tlf: +47 66775590

Greece
TEVA HELLAS A.E.
Tel: +30 2118805000

Austria
ratiopharm Arzneimittel Vertriebs-GmbH
Tel: +43 1970070

Spain
Teva Pharma, S.L.U.
Tel: +34 913873280

Poland
Teva Pharmaceuticals Polska Sp. z o.o.
Tel.: +48 223459300

France
Teva Santé
Tél: +33 155917800

Portugal
Teva Pharma - Produtos Farmacêuticos, Lda.
Tel: +351 214767550

Croatia
Pliva Hrvatska d.o.o.
Tel: +385 13720000

Romania
Teva Pharmaceuticals S.R.L.
Tel: +40 212306524

Ireland
Teva Pharmaceuticals Ireland
Tel: +44 2075407117

Slovenia
Pliva Ljubljana d.o.o.
Tel: +386 15890390

Iceland
Teva Pharma Iceland ehf.
Sími: +354 5503300

Slovakia
TEVA Pharmaceuticals Slovakia s.r.o.
Tel: +421 257267911

Italy
Teva Italia S.r.l.
Tel: +39 028917981

Finland
Teva Finland Oy
Puh/Tel: +358 201805900

Cyprus
TEVA HELLAS A.E.
Greece
Tel: +30 2118805000

Latvia
UAB Teva Baltics Latvia branch
Tel: +371 67323666

United Kingdom (Northern Ireland)
Teva Pharmaceuticals Ireland
Ireland
Tel: +44 2075407117

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 healthcare professionals only:

Potactasol
INSTRUCTIONS FOR USE
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 of water for injections (due to a 10% overfill)
• Potactasol 4 mg with 4 ml of water for injections

Reconstitution will result in a concentrate containing 1 mg of topotecan per ml.
This concentrate (1 mg/ml) must be further diluted before administration.
To obtain a final concentration in the infusion solution between
25 and 50 micrograms/ml, the volume of the reconstituted concentrate corresponding to the individually calculated dose should be further diluted with either sodium chloride 9 mg/ml (0.9%) or glucose 5% w/v, for example:

Storage after reconstitution and dilution
The chemical and physical stability of the concentrate has been demonstrated for 24 hours at a temperature of 25 ± 2°C under normal light conditions, and for 24 hours at a temperature of 2°C to 8°C when protected from light.
The chemical and physical stability of the solution obtained after dilution of the concentrate in an injectable solution of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml solution for infusion (5%) has been demonstrated for 4 hours at 25 ± 2°C under normal light conditions. Concentrated samples were reconstituted and stored at 25 ± 2°C for 12 hours and 24 hours respectively after reconstitution, and then diluted.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the in-use storage times and storage conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C, provided that reconstitution/dilution has been carried out under validated and controlled aseptic conditions.

Handling and disposal
Standard procedures for the safe handling and disposal of antineoplastic medicinal products should be followed:

• Personnel must be trained in the proper methods of dilution of the medicinal product.
• Pregnant personnel must be excluded from activities involving the use of this medicinal product.
• Personnel handling the medicinal product during reconstitution and dilution must wear protective clothing, including mask, goggles, and gloves.
• In case of accidental contact with skin or eyes, immediately flush with large amounts of water.
• All equipment and materials used for administration and cleaning, including gloves, must be placed in bags intended for disposal of high-risk materials, to be incinerated at high temperature.