Tiotepa Kabi 15 mg powder for concentrate for infusion solution EFG

Package leaflet: Information for the user

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 questions, ask your doctor.
• If you get any side effects, talk to your doctor, including any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

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

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

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

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

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

Do not use Tiotepa Kabi

• if you are allergic to tiotepa,
• if you are pregnant or think you might be pregnant,
• if you are breastfeeding,

or if you are due to receive the yellow fever vaccine or other live virus or bacterial vaccines.

Warnings and precautions

Inform your doctor if you have:

• liver or kidney problems,
• heart or lung problems,
• seizures or a history of seizures (if you have been treated with phenytoin or fosphenytoin).

Since tiotepa destroys bone marrow cells responsible for producing blood cells, you will need periodic blood tests during treatment to monitor your blood cell counts.

To prevent and treat infections, you will be given anti-infective agents.

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

Other medicines and Tiotepa Kabi

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding and fertility

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

Both women and men receiving Tiotepa Kabi must use effective methods of contraception during treatment.

After stopping treatment, women should continue using effective contraception for at least 6 months and men for at least 3 months.

It is unknown whether this medicine is excreted in human milk. As a precaution, women should not breastfeed during treatment with tiotepa.

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

If having children after completion of therapy is desired, genetic counselling is recommended in advance.

Driving and use of machines

Some adverse reactions of tiotepa, such as dizziness, headache and blurred vision, may affect your ability to drive or operate machinery. If you experience these adverse effects, do not drive or operate machinery.

Tiotepa Kabi contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial; therefore, it is considered 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 condition.

How Tiotepa Kabi is administered

Tiotepa must be administered by a qualified healthcare professional as an intravenous infusion (a 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. Treatment may last up to 5 days. The frequency of administration and duration of treatment will depend on your condition.

4. Possible adverse effects

Like all medicines, Tiotepa Kabi may cause adverse effects, although not everyone experiences them.

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

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

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

Adverse effects of tiotepa occur at certain frequencies, defined as follows:

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

• increased susceptibility to infections
• generalized inflammation (septicemia)
• decreased white blood cell, platelet, and red blood cell counts (anemia)
• attack by transplanted cells against your body (graft-versus-host disease)
• dizziness, headache, blurred vision
• uncontrolled body tremors (seizures)
• tingling, prickling, or numbness sensation (paresthesia)
• partial loss of mobility
• cardiac arrest
• nausea, vomiting, diarrhea
• inflammation of the oral mucosa (mucositis)
• irritation of stomach, esophagus, intestine
• inflammation of the colon
• anorexia, loss of appetite
• elevated blood glucose levels
• rash, pruritus, skin peeling
• skin color changes (should not be confused with jaundice – see below)
• redness of the skin (erythema)
• hair loss
• back and abdominal pain, pain
• muscle and joint pain
• abnormal electrical activity in the heart (arrhythmia)
• inflammation of lung tissue
• enlarged liver
• impaired function of certain organs
• blockage of a liver vein (veno-occlusive disease, VOD)
• yellowing of the skin and eyes (jaundice)
• hearing impairment
• lymphatic obstruction
• high blood pressure
• enlarged liver, elevated renal and digestive enzymes
• abnormal blood electrolyte levels
• weight gain
• fever, general weakness, chills
• bleeding (hemorrhage)
• nosebleeds
• generalized 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 testosterone production
• insufficient thyroid hormone production
• reduced pituitary activity
• confusion

Frequent adverse 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)
• disturbance in heart rhythm
• heart failure
• cardiovascular insufficiency
• oxygen deficiency
• fluid accumulation in the lungs (pulmonary edema)
• pulmonary hemorrhage
• respiratory arrest
• blood in the urine (hematuria) and moderate renal failure
• inflammation of the urinary bladder
• discomfort during urination and decreased urine production (dysuria and oliguria)
• increased levels of nitrogen-containing components in the blood (elevated BUN)
• cataracts
• liver failure
• cerebral hemorrhage
• cough
• constipation and gastric discomfort
• intestinal obstruction
• stomach perforation
• changes in muscle tone
• general lack of coordination of muscular movements
• bruising associated with low platelet count
• menopausal symptoms
• cancer (secondary primary neoplasms)
• impairment of brain function
• male and female infertility

Uncommon adverse 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 tissue (myocarditis)
• abnormal heart disease (cardiomyopathy)

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

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse 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 stated on the container after "EXP". The expiry date refers to the last day of the month indicated.

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

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

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

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

6. Contents of the container 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).
• Another excipient is sodium carbonate.

Appearance of the medicinal product and contents of the container

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 Authorization Holder and Manufacturer

Marketing Authorization 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 medicinal product is authorized in the Member States of the European Economic Area under the following names:

Dates of the last review of this leaflet:

07/2024

Other sources of information

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

This information is intended for healthcare professionals only:

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. PRESENTATION

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

2. SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

General

Appropriate procedures for handling and disposal of antineoplastic drugs must be observed. All transfer procedures must strictly follow aseptic techniques, preferably using a vertical laminar flow safety cabinet. As with other cytotoxic compounds, extreme caution must be exercised during handling and preparation of tiotepa solutions to avoid accidental contact with skin or mucous membranes. Topical reactions may occur following accidental exposure to tiotepa. Therefore, the use of gloves is recommended when preparing the infusion solution. If tiotepa solution comes into accidental contact with the skin, the area should be immediately and thoroughly washed with soap and water. If tiotepa comes into contact with mucous membranes, they should be thoroughly rinsed with water.

Dose and dosage calculation in pediatric and adult patients

Refer to section 4.2 of the Summary of Product Characteristics for dose and dosage calculation 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 injections.

Using a syringe equipped with a needle, withdraw 1.5 ml of sterile water for injections under aseptic conditions.

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

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

Using a syringe equipped with a needle, withdraw 10 ml of sterile water for injections under aseptic conditions.

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

Remove the syringe and needle and mix manually by repeated inversion of the vial.

Only clear, colorless solutions free from particles should be used. Reconstituted solutions may occasionally appear opalescent; such solutions may still be administered.

Further dilution in the infusion bag

The reconstituted solution is hypotonic and must be diluted prior to administration with 500 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection (1,000 ml if the dose exceeds 500 mg), or with an appropriate volume of 9 mg/ml (0.9 %) sodium chloride solution to achieve a final tiotepa concentration between 0.5 and 1 mg/ml.

Administration

Tiotepa Kabi solution for infusion must be visually inspected for particulate matter prior to administration. Solutions containing precipitates should be discarded.

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

The indwelling catheter should be flushed with approximately 5 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection before and after each infusion.

Disposal

Tiotepa Kabi is for single use only.

Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations.