TIOTEPA KABI 15 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Tiotepa Kabi 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi 100 mg powder for concentrate for solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Tiotepa Kabi and what is it used for

Tiotepa Kabi contains tiotepa as the active substance, a medicine that belongs to the group of alkylating agents.

Tiotepa Kabi is used to prepare the patient for a bone marrow transplant. It works by destroying the cells of the bone marrow. This allows the patient to receive a transplant of new bone marrow cells (haematopoietic stem cells), which in turn enable the body to produce healthy blood cells.

Tiotepa Kabi can be used in adults, children, and adolescents.

2. What you need to know before you use Tiotepa Kabi

Do not use Tiotepa Kabi

• if you are allergic to tiotepa,
• if you are pregnant or think you may be pregnant,
• if you are breast-feeding,

if you are going to receive the yellow fever vaccine with live virus and bacterial vaccines.

Warnings and precautions

Tell your doctor if you have:

• liver or kidney problems,
• heart or lung problems,
• seizures/epileptic fits or have had them in the past (if you have been treated with phenytoin or fosphenytoin).

Since tiotepa destroys the bone marrow cells responsible for producing blood cells, you will need to have regular blood tests during treatment to check your cell counts.

For the prevention and treatment of infections, you will be given anti-infectives.

Tiotepa Kabi may cause another type of cancer in the future. Your doctor will explain this type of risk to you.

Other medicines and Tiotepa Kabi

Tell your doctor if you are using, have recently used, or might use any other medicines.

Pregnancy, breast-feeding, and fertility

Tell your doctor if you are pregnant or think you may be pregnant before receiving tiotepa. You must not use tiotepa during pregnancy.

Both women and men using Tiotepa Kabi must use effective contraceptive methods during treatment.

After stopping treatment, women must use effective contraceptive methods for at least 6 months and men for at least 3 months.

It is not known if this medicine is excreted in breast milk. As a precaution, women must not breast-feed during treatment with tiotepa.

Tiotepa may affect male and female fertility. Male patients should seek advice on sperm preservation before starting treatment.

If you wish to have children after therapy, genetic counseling is recommended beforehand.

Driving and using machines

Some adverse reactions of tiotepa, such as dizziness, headache, and blurred vision, may affect your ability to drive and use machines. If you notice these side effects, do not drive or use machines.

Tiotepa Kabi contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial; it is essentially "sodium-free".

3. How to use Tiotepa Kabi

Your doctor will calculate the dose based on your body surface area or body weight and your disease.

How Tiotepa Kabi is administered

Tiotepa must be administered by a qualified healthcare professional via intravenous infusion (drip into a vein) after dilution of each vial. Each infusion lasts 2-4 hours.

Frequency of administration

You will receive infusions every 12 or 24 hours. The treatment may last up to 5 days. The frequency of administration and the duration of treatment will depend on your disease.

4. Possible side effects

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

Some more serious side effects of treatment with tiotepa or the transplant procedure are:

• decrease in blood cell counts (expected effect of the medicine as preparation for your transplant)
• infection
• liver problems, such as blockage of a liver vein
• attack of the graft against your body (graft-versus-host disease)
• respiratory complications

Your doctor will monitor your blood cell counts and liver enzymes regularly to detect and treat these events.

The side effects of tiotepa occur with certain frequencies, which are defined below:

Very common side effects (may affect more than 1 in 10 people)

• increased risk of infections
• generalized inflammation (septicemia)
• decrease in white blood cell, platelet, and red blood cell count (anemia)
• attack of the transplanted cells against your body (graft-versus-host disease)
• dizziness, headache, blurred vision
• uncontrolled body tremors (seizures)
• tingling, pinching, or numbness (paresthesia)
• partial loss of mobility
• cardiac arrest
• nausea, vomiting, diarrhea
• inflammation of the oral mucosa (mucositis)
• irritation of the stomach, esophagus, intestine
• inflammation of the colon
• loss of appetite, anorexia
• elevated blood glucose
• rash, itching, peeling
• change in skin color (not to be confused with jaundice - see below)
• redness of the skin (erythema)
• hair loss
• back and abdominal pain
• muscle and joint pain
• abnormal heart rhythm
• inflammation of lung tissue
• enlargement of the liver
• altered function of some organs
• blockage of a liver vein (veno-occlusive disease, VOD)
• yellowing of the skin and eyes (jaundice)
• hearing impairment
• lymphatic obstruction
• high blood pressure
• enlargement of the liver, elevated kidney and digestive enzymes
• abnormal blood electrolyte values
• weight gain
• fever, general weakness, chills
• bleeding (hemorrhage)
• nosebleed
• general swelling due to fluid retention (edema)
• pain or inflammation at the injection site
• eye infection (conjunctivitis)
• decreased sperm count
• vaginal bleeding
• absence of menstrual periods (amenorrhea)
• memory loss
• delayed weight and height gain
• bladder problems
• insufficient production of testosterone
• insufficient production of thyroid hormones
• reduced activity of the pituitary gland
• state of confusion

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

• anxiety, confusion
• abnormal dilation of one of the arteries in the brain (intracranial aneurysm)
• elevated creatinine
• allergic reactions
• blockage of a blood vessel (embolism)
• abnormal heart rhythm
• heart failure
• cardiovascular disability
• oxygen deficiency
• fluid accumulation in the lungs (pulmonary edema)
• lung bleeding
• respiratory arrest
• blood in the urine (hematuria) and moderate kidney failure
• inflammation of the urinary bladder
• discomfort when urinating and decreased urine production (dysuria and oliguria)
• increased amount of nitrogen components in the blood (elevated BUN)
• cataracts
• liver failure
• brain bleeding
• cough
• constipation and stomach discomfort
• intestinal obstruction
• stomach perforation
• changes in muscle tone
• general lack of coordination of muscle movements
• hematomas associated with low platelet count
• menopausal symptoms
• cancer (secondary primary neoplasms)
• altered brain function
• male and female infertility

Uncommon side effects (may affect up to 1 in 100 people)

• inflammation and peeling of the skin (erythrodermic psoriasis)
• delirium, nervousness, hallucinations, agitation
• gastrointestinal ulcer
• inflammation of the heart muscle (myocarditis)
• abnormal heart disease (myocardial disease)

Frequency not known (frequency cannot be estimated from the available data)

• increased blood pressure in the arteries (blood vessels) of the lungs (pulmonary arterial hypertension)
• severe skin damage (e.g. severe lesions, blisters, etc.) that can affect the entire body surface, which can be fatal
• damage to a component of the brain (the so-called white matter) that can be fatal (leukoencephalopathy).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tiotepa Kabi

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

Do not use Tiotepa Kabi after the expiry date which is stated on the carton after "EXP". The expiry date is the last day of the month shown.

Store and transport refrigerated (2°C-8°C). Do not freeze.

After reconstitution, the product is stable for 8 hours when stored at 2°C-8°C.

After dilution, the product is stable for 24 hours when stored at 2°C-8°C and for 4 hours when stored at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the user will be responsible for the storage periods during use and the storage conditions prior to use, which normally will not exceed 24 hours at 2-8°C.

Disposal of unused medicine and all materials that have been in contact with it will be carried out in accordance with local regulations.

6. Contents of the pack and other information

Composition of Tiotepa Kabi

• The active substance is tiotepa.

Tiotepa Kabi 15 mg powder for concentrate for solution for infusion EFG

One vial contains 15 mg of tiotepa.

Tiotepa Kabi 100 mg powder for concentrate for solution for infusion EFG

One vial contains 100 mg of tiotepa.

• After reconstitution, each ml contains 10 mg of tiotepa (10 mg/ml).
• Other excipients are sodium carbonate

Appearance and pack of the product

Tiotepa Kabi 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi is a white powder supplied in a glass vial containing 15 mg of tiotepa.

Tiotepa Kabi 100 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi is a white powder supplied in a glass vial containing 100 mg of tiotepa.

Each carton contains 1 vial.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Fresenius Kabi España, S.A.U.

Torre Mapfre – Vila Olímpica

Marina, 16-18.

08005 Barcelona (Spain)

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

This medicine is authorised in the Member States of the European Economic Area under the following names:

Dates of the last revision of this leaflet:

07/2024

Other sources of information

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

PREPARATION GUIDE

Tiotepa Kabi 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi 100 mg powder for concentrate for solution for infusion EFG

Read this guide before preparing and administering Tiotepa Kabi.

1.

Tiotepa Kabi is supplied as 15 mg and 100 mg powder for concentrate for solution for infusion. Tiotepa Kabi must be reconstituted and diluted before administration.

2.

Generalities

Proper handling and disposal procedures for antineoplastic medications will be taken into account. All transfer procedures must strictly comply with aseptic techniques, preferably using a vertical laminar flow safety hood. As with other cytotoxic compounds, extreme caution will be exercised during the handling and preparation of tiotepa solutions to avoid accidental contact with the skin or mucous membranes. Topical reactions associated with accidental exposure to tiotepa may occur. Therefore, the use of gloves is recommended during the preparation of the solution for infusion. If the tiotepa solution comes into accidental contact with the skin, it should be washed immediately with water and soap. If tiotepa comes into accidental contact with the mucous membranes, they should be washed well with water.

Dose calculation and posology in pediatric and adult patients.

Refer to section 4.2 of the technical data sheet for dose calculation and posology in pediatric and adult patients.

Reconstitution

Tiotepa Kabi 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi must be reconstituted with 1.5 ml of sterile water for injectable preparations.

Using a syringe with a needle, aseptically withdraw 1.5 ml of sterile water for injectables.

Tiotepa Kabi 100 mg powder for concentrate for solution for infusion EFG

Tiotepa Kabi must be reconstituted with 10 ml of sterile water for injectable preparations.

Using a syringe with a needle, aseptically withdraw 10 ml of sterile water for injectables.

Inject the contents of the syringe into the vial by piercing the rubber stopper.

Remove the syringe and needle, and manually mix by repeatedly inverting the vial.

Only clear, colorless solutions without particles will be used. Reconstituted solutions may occasionally exhibit opalescence; such solutions may still be administered.

Additional dilution in the infusion bag

The reconstituted solution is hypotonic and must be diluted before administration with 500 ml of injectable solution containing 9 mg/ml of sodium chloride (0.9%) for injectables (1000 ml if the dose is greater than 500 mg) or with an appropriate volume of 9 mg/ml (0.9%) sodium chloride to achieve a final tiotepa concentration of between 0.5 and 1 mg/ml.

Administration

Tiotepa Kabi infusion solution must be visually inspected for the presence of particles before administration. Solutions containing precipitates must be discarded.

The infusion solution should be administered to patients using an infusion set with a 0.2 µm in-line filter. Filtration does not alter the potency of the solution.

Before and after each infusion, the permanent catheter should be flushed with approximately 5 ml of injectable solution containing 9 mg/ml of sodium chloride (0.9%).

Elimination

Tiotepa Kabi is for single use.

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.