Topotecan Sandoz 1 mg/ml concentrate for solution for infusion – patient leaflet, side effects, dosage

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

Topotecan Sandoz helps to destroy tumours. A doctor or a nurse will give you the medicine as an infusion into a vein in hospital.

Topotecan Sandoz is used to treat

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

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

2. What you need to know before you are given Topotecan Sandoz

You should not receive Topotecan Sandoz

• 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 counts are too low. Your doctor will tell you whether this is the case, based on the results of your last blood test.

Tell your doctor if any of these applies to you.

Warnings and precautions

Before you are given this medicine your doctor needs to know:

• if you have any kidney or liver problems. Your dose of Topotecan Sandoz may need to be adjusted.
• if you are pregnant or plan to become pregnant. See section “Pregnancy and breast-feeding” below.
• if you plan to father a child. See section “Pregnancy and breast-feeding” below.

• •

  Tell your doctor if any of these applies to you.

Other medicines and Topotecan Sandoz Tell your doctor if you are taking, have recently taken, or might take any other medicines, including any herbal products or medicines obtained without a prescription.

Remember to tell your doctor if you start to take any other medicines while you are on Topotecan Sandoz.

Pregnancy and breast-feeding

Topotecan Sandoz is not recommended for pregnant women. It may harm a baby conceived before, during or soon after treatment. You should use an effective method of contraception. Ask your doctor for advice. Do not try to become pregnant until a doctor advises you it is safe to do so.

Male patients, who wish to father a child should ask their doctor for family planning advice 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 Sandoz. Do not restart breast-feeding until the doctor tells you it is safe to do so.

Driving and using machines

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

3. How Topotecan Sandoz is used

The dose of Topotecan Sandoz you are given will be worked out by your doctor, based on:

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

The usual dose

Ovarian and small cell lung cancer:

1.5 mg per square metre of body surface area per day. You will have treatment once a day for 5 days. This pattern of treatment will normally be repeated every three weeks.

Cervical cancer:

0.75 mg per square metre of body surface area per day. You will have treatment once a day for 3 days. . This pattern of treatment will normally be repeated every three weeks.

When treating cervical cancer, Topotecan Sandoz is combined with another medicine, called cisplatin. Your doctor will determine the correct dose of cisplatin

The treatment may vary, depending on the results of your regular blood tests.

How Topotecan Sandoz is given

A doctor or nurse will administer Topotecan Sandoz as an infusion into your arm lasting about 30 minutes.

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 common side effects may affect more than 1 in 10 people treated with topotecan:

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

This rare side effect may affect up to 1 in 1,000 people treated with topotecan:

• Lung inflammation ( interstitial lung disease): You are most at risk if you have existing lung disease, have had radiation treatment to your lungs, or have previously taken medicines that caused lung damage. Signs include::

  • difficulty breathing
  • cough
  • fever

Tell your doctor immediately if you get any symptoms of these conditions, as hospitalisation may be necessary.

Very common side effects

These may affect more than 1 in 10 people treated with topotecan

• Feeling generally weak and tired (temporary anaemia) In some cases you may need a blood transfusion.
• Unusual bruising or bleeding, caused by a decrease in the number of clotting cells in the blood. 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 minimise the risk of bleeding.
• Weight loss and loss of appetite (anorexia); tiredness; weakness.
• 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

These may affect up to 1 in 10 people treated with topotecan:

• Allergic or hypersensitivity reactions (including rash).
• Yellow skin.
• Feeling unwell.
• Itching sensation.

Rare side effects

These may affect up to 1 in 1,000 people treated with topotecan:

• 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).

Side effects with frequency not known

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

• Severe stomach pain, nausea, vomiting of blood, black 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 gut [mucosal inflammation]).

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 Topotecan Sandoz. Those effects are described in the cisplatin patient leaflet.

Reporting of side effects

If you get any any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in Google play or Apple App store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Topotecan Sandoz

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and the vial after “EXP”. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

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

Do not freeze.

Store in a refrigerator (2°C – 8°C).

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

Do not freeze.

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 Sandoz contains

The active substance is topotecan.

One milliliter concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride).

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

Each vial of 3 ml contains 3 mg topotecan (as hydrochloride).

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

The other ingredients are tartaric acid, diluted hydrochloric acid and water for injections

What Topotecan Sandoz looks like and contents of the pack

This medicinal product is presented as a concentrate for solution for infusion.

The concentrate is a clear, yellow solution, practically free from visible particles contained in a colourless type 1 glass vials with grey rubber stoppers, and aluminium seals with plastic flip-off caps, with or without a plastic protection (Onco-Safe or Sleeving). “Onco-Safe” and Sleeving do not come into contact with the medicine and provide additional transport protection, which increases the safety for the medical and pharmaceutical personnel. The vials are sealed with aluminium crimp caps.

Pack sizes:

1 x 1 ml, 5 x 1 ml, 10 x 1 ml,

1 x 3 ml, 5 x 3 ml, 10 x 3 ml,

1 x 4 ml, 5 x 4 ml, 10 x 4 ml,

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Sandoz Limited

Park View, Riverside Way

Watchmoor Park

Camberley, Surrey

GU15 3YL

United Kingdom

Manufacturer

Ebewe Pharma Ges.m.b.H. Nfg. KG

A-4866 Unterach, Austria

This leaflet was last revised in 07/2021.

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

Special precautions for disposal and other handling

Inspection prior to use

As with all parenteral drug products, Topotecan Sandoz concentrate for solution for infusion should be inspected visually for particulate matter and discolouration prior to use. Do not use Topotecan Sandoz if you notice certain signs of deteriorations.

Instruction for dilution

Must be diluted before use.

Further dilution of the appropriate volume of the concentrate for solution for infusion with either 0.9 % sodium chloride intravenous infusion or 5 % glucose intravenous infusion is required to a final concentration of between 10 and 50 microgram/ml (0.01 mg/ml, 0.025 mg/ml and 0.05 mg/ml).

The required volume can be directly withdrawn from the vial.

More than one vial might be necessary to obtain the required dose for the patient. Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding volume containing 1 mg/ml topotecan from the appropriate number of vials using graduated syringes. For example, a dose of 2.7 mg topotecan would require 2.7 ml topotecan concentrate for solution for infusion.

Inject the required volume into a 100 ml infusion bag or bottle containing either 5% glucose solution or 0.9% sodium chloride solution.

If a dose greater than 5mg of topotecan is required, use a larger volume of the infusion vehicle so that a concentration of 0.05 mg/ml topotecan is not exceeded.

Mix the infusion bag or bottle manually using a rocking motion.

General precaution

The normal procedures for proper handling and disposal of anticancer medicinal products should be adopted, namely:

• Staff should be trained to dilute the medicinal product.
• Pregnant staff should be excluded from working with this medicinal product.
• Personnel handling this medicinal product during dilution should wear protective clothing, including mask, goggles and gloves.
• 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.
• Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.

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

The medicinal product is for single use only.

Incompatibilities

This medicinal product must not be mixed with other medicinal products except with glucose 5 % or sodium chloride 0.9 %.

Posology and method of administration

The use of topotecan should be confined to units specialised in the administration of cytotoxic chemotherapy. Topotecan should only be administered under the supervision of a physician experienced in the use of chemotherapy (see section 6.6).

Posology

When used in combination with cisplatin, the full prescribing information for cisplatin should be consulted.

Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of ≥ 1.5 x 10⁹/l, a platelet count of ≥ 100 x 10⁹/l and a haemoglobin level of ≥ 9 g/dl (after transfusion if necessary).

Ovarian and Small Cell Lung Carcinoma

Initial dose

The recommended dose of topotecan is 1.5 mg/m² body surface area per day administered by intravenous infusion over 30 minutes daily for five consecutive days with a three week interval between the start of each course. If well tolerated, treatment may continue until disease progression (see sections 4.8 and 5.1).

Subsequent doses

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

Standard oncology practice for the management of neutropenia is either to administer topotecan with other medicinal products (e.g. G-CSF) or to reduce the dose to maintain neutrophil counts.

If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 10⁹/l) for seven days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.25 mg/m²/day to 1.25 mg/m²/day (or subsequently down to 1.0 mg/m²/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 10⁹/l. In clinical studies, topotecan was discontinued if the dose had been reduced to 1.0 mg/m²/day and a further dose reduction was required to manage adverse effects.

Cervical carcinoma

Initial dose

The recommended dose of topotecan is 0.75 mg/m²/day administered as a 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 and following the topotecan dose. This treatment schedule is repeated every 21 days for six courses or until progressive disease.

Subsequent doses

Topotecan should not be re-administered unless the neutrophil count is ≥1.5 x 10⁹/l, the platelet count is ≥100 x 10⁹/l, and the haemoglobin level is ≥ 9g/dl (after transfusion if necessary).

Standard oncology practice for the management of neutropenia is either to administer topotecan with other medicinal products (e.g. G-CSF) or to reduce the dose to maintain neutrophil counts.

If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count ≤0.5 x 10⁹/l) for seven days or more, or severe neutropenia associated with fever or infection or who have had treatment delayed due to neutropenia, the dose should be reduced by 20% to 0.60 mg/m²/day for subsequent courses (or subsequently down to 0.45 mg/m²/day if necessary).

Doses should be similarly reduced if the platelet count falls below 25 x 10⁹/l.

Special populations

Patients with renal impairment

Monotherapy (ovarian and small cell lung carcinoma)

There is insufficient experience with the use of topotecan in patients with severely impaired renal function (creatinine clearance <20 ml/min). Use of topotecan in this group of patients is not recommended (see section 4.4).

Limited data indicate that the dose should be reduced in patients with moderate renal impairment. The recommended monotherapy dose of topotecan in patients with ovarian or small cell lung carcinoma and a creatinine clearance between 20 and 39 ml/min is 0.75 mg/m² /day for five consecutive days.

Combination therapy (cervical carcinoma)

In clinical studies with topotecan in combination with cisplatin for the treatment of cervical cancer, therapy was only initiated in patients with serum creatinine less than or equal to 1.5 mg/dL. If, during topotecan/cisplatin combination therapy serum creatinine exceeds 1.5 mg/dL, it is recommended that the full prescribing information be consulted for any advice on cisplatin dose reduction/continuation.

If cisplatin is discontinued, there are insufficient data regarding continuing monotherapy with topotecan in patients with cervical cancer.

Patients with hepatic impairment

A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) were given intravenous topotecan at 1.5 mg/m²/day for five days every three weeks. A reduction in topotecan clearance was observed. However, there are insufficient data available to make a dose recommendation for this patient group (see section 4.4).

There is insufficient experience with the use of topotecan in patients with severely impaired hepatic function (serum bilirubin ≥10 mg/dl) due to cirrhosis. Topotecan is not recommended to be used in this patient group (see section 4.4).

Paediatric population

Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.

Method of administration

Topotecan Sandoz must be further diluted before use (see section 6.6).

Storage and Shelf life

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

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Unopened Vials

30 months

In-use stability after dilution:

Chemical and physical in-use stability after dilution has been demonstrated for 7 days when the product is diluted to a concentration of 0.01 – 0.05 mg/ml with glucose 5% or sodium chloride 0.9% and stored between 2°C to 8°C and room temperature (20°C to 25°C).

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 °C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.