Thiotepa fresenius kabi

Package leaflet: Information for the user

Thiotepa Fresenius Kabi, 15 mg, powder for concentrate for solution for infusion
Thiotepa Fresenius Kabi, 100 mg, powder for concentrate for solution for infusion
Thiotepum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor immediately. See section 4.

Contents of the leaflet

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

1. What Thiotepa Fresenius Kabi is and what it is used for

Thiotepa Fresenius Kabi contains the active substance thiotepa, which belongs to the group of alkylating agents.
Thiotepa Fresenius Kabi is used to prepare the patient for bone marrow transplantation.
The medicine works by destroying bone marrow cells. This allows transplantation of new bone marrow cells (haematopoietic stem cells), enabling the body to produce healthy blood cells.
Thiotepa Fresenius Kabi may be used in adults as well as in children and adolescents.

2. Important information before using Thiotepa Fresenius Kabi

When not to use Thiotepa Fresenius Kabi

• if the patient is allergic to thiotepa,
• if the patient is pregnant or suspects she may be pregnant,
• if the patient is breastfeeding,
• during administration of the yellow fever vaccine or vaccines containing live viruses and bacteria.

Warnings and precautions
Tell your doctor if the patient:

• has impaired liver or kidney function,
• has heart or lung disease,
• has seizures (epilepsy) or a history of seizures (especially if treated with phenytoin or fosphenytoin).

Because thiotepa destroys bone marrow cells responsible for blood cell production,
regular blood tests will be performed during treatment to monitor blood cell counts.
Antimicrobial medications will be used to prevent and treat infections.
Thiotepa may cause a different type of cancer in the future. Your doctor will provide information about
this risk.

Thiotepa Fresenius Kabi and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to take.

Pregnancy, breastfeeding and fertility
Before starting treatment with Thiotepa Fresenius Kabi, inform your doctor if the patient is pregnant or suspects she may be pregnant. Thiotepa Fresenius Kabi must not be used during pregnancy.
Both women and men receiving thiotepa must use effective contraception during treatment.
Women must continue using effective contraception for at least 6 months after completion of treatment, and men for at least 3 months.
It is not known whether the drug passes into human milk. As a precaution, women are advised not to breastfeed during treatment with Thiotepa Fresenius Kabi.
Thiotepa Fresenius Kabi may impair fertility in both men and women. Before starting treatment, men should consider sperm preservation.
If having children after treatment is planned, genetic counselling is recommended.

Driving and operating machinery
Some adverse effects of thiotepa, such as dizziness, headache, and blurred vision, may affect the ability to drive or operate machinery.
If such symptoms occur, the patient should not drive or operate machinery.

Thiotepa Fresenius Kabi contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning it is considered "sodium-free".

3. How to use Thiotepa Fresenius Kabi

The doctor will determine the dose of the medicine depending on the body surface area or body weight, and according to the disease.
How Thiotepa Fresenius Kabi is administered
The medicine is administered by qualified medical personnel as an infusion, after dissolving the contents of the vial.
The infusion lasts from 2 to 4 hours.
Frequency of administration
The infusion is given every 12 hours or every 24 hours. The duration of treatment is up to 5 days.
The frequency of administration and duration of treatment depend on the type of disease.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most serious adverse reactions associated with the use of thiotepa or the transplant procedure are:

• reduction in circulating blood cells (an intended effect of the drug to prepare for transplantation),
• infection,
• liver disorders including hepatic vein occlusion,
• attack of the body by the transplant (graft-versus-host disease),
• respiratory complications. The doctor will regularly monitor blood cell counts and liver enzyme activity to detect and treat these adverse reactions.

Adverse reactions associated with the use of thiotepa may occur with a defined frequency as follows:
Very common (may occur in more than 1 in 10 patients):

• increased susceptibility to infections,
• systemic inflammatory condition (sepsis),
• decreased number of white blood cells, platelets and red blood cells (anaemia),
• attack of the body by transplanted cells (graft-versus-host disease),
• dizziness, headache, blurred vision,
• uncontrolled body tremors (seizures),
• tingling, pricking or numbness sensation (sensory disturbances),
• partial loss of motor ability,
• cardiac arrest,
• nausea, vomiting, diarrhoea,
• inflammation of the mucous membrane of the mouth,
• irritation of the stomach, oesophagus, intestines,
• inflammation of the large intestine,
• loss of appetite, decreased appetite,
• increased blood glucose concentration,
• skin rash, itching, skin eruptions,
• skin pigmentation disorders (do not confuse with jaundice - see below),
• skin redness (erythema),
• hair loss,
• back and abdominal pain, pain,
• muscle and joint pain,
• disturbances in electrical heart function (arrhythmia),
• inflammation of lung tissue,
• enlarged liver,
• organ dysfunction,
• hepatic vein occlusion (veno-occlusive disease),
• yellowing of the skin and eyes (jaundice),
• hearing disorders,
• lymphatic vessel obstruction,
• hypertension,
• increased activity of liver, kidney and digestive enzymes,
• electrolyte disturbances,
• weight gain,
• fever, general weakness, chills,
• bleeding (haemorrhage),
• nosebleed,
• generalized swelling due to fluid retention,
• pain and inflammation at the injection site,
• eye infection (conjunctivitis),
• decreased sperm count,
• vaginal bleeding,
• absence of menstrual bleeding,
• memory loss,
• delayed weight gain and growth disorders,
• urinary bladder dysfunction,
• insufficient testosterone production,
• insufficient thyroid hormone production,
• pituitary insufficiency,
• confusion.

Common (may occur in less than 1 in 10 patients):

• anxiety, disorientation,
• abnormal dilation of one of the brain arteries (intracranial aneurysm),
• elevated creatinine levels,
• allergic reactions,
• blockage of blood vessels (embolism),
• heart rhythm disturbances,
• heart failure,
• cardiogenic shock,
• hypoxia,
• fluid accumulation in the lungs (pulmonary oedema),
• pulmonary haemorrhage,
• respiratory arrest,
• presence of blood in urine (haematuria) and moderate kidney failure,
• bladder inflammation,
• discomfort during urination and reduced urine output (dysuria and oliguria),
• increased nitrogen-containing components in blood (elevated BUN, blood urea nitrogen),
• cataract,
• liver failure,
• cerebral haemorrhage,
• cough,
• constipation and stomach upset,
• intestinal obstruction,
• gastric perforation,
• muscle tone disturbances,
• severe movement coordination disturbances,
• bruising due to low platelet count,
• menopausal symptoms,
• malignant tumour (other, new tumour process),
• brain function disorders,
• infertility in men and women.

Uncommon (may occur in less than 1 in 100 patients):

• skin inflammation and peeling (erythroderma exfoliativa),
• delirium, nervousness, hallucinations, agitation,
• gastric and intestinal ulceration,
• inflammation of heart muscle tissue (myocarditis),
• abnormal heart condition (cardiomyopathy).

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

• elevated blood pressure in the pulmonary arteries (pulmonary arterial hypertension),
• severe skin damage (e.g. severe lesions, blisters, etc.), possibly affecting the entire body surface and even life-threatening,
• damage to part of the brain (so-called white matter), potentially life-threatening (leukoencephalopathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Thiotepa Fresenius Kabi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial following EXP.
The expiry date refers to the last day of the stated month.
Store and transport in a refrigerated state (2°C – 8°C). Do not freeze.
After reconstitution, the medicine is stable for 8 hours when stored at 2°C–8°C.
After dilution, the medicine 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 medicine should be used immediately. If the medicine is not used immediately,
the user is responsible for the storage duration and conditions prior to use.
The storage period should not exceed 24 hours at 2–8°C.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

What Thiotepa Fresenius Kabi contains

• The active substance is tiotepa.
  Thiotepa Fresenius Kabi, 15 mg, powder for solution for concentrate for infusion
  One vial contains 15 mg of tiotepa.

Thiotepa Fresenius Kabi, 100 mg, powder for solution for concentrate for infusion
One vial contains 100 mg of tiotepa.
After reconstitution, each mL of solution contains 10 mg of tiotepa (10 mg/mL).

• The other ingredient of the medicine is sodium carbonate.

What Thiotepa Fresenius Kabi looks like and contents of the pack
Thiotepa Fresenius Kabi, 15 mg, powder for solution for concentrate for infusion
Thiotepa Fresenius Kabi is a white powder or tablet in a glass vial containing 15 mg of tiotepa.
Thiotepa Fresenius Kabi, 100 mg, powder for solution for concentrate for infusion
Thiotepa Fresenius Kabi is a white powder or tablet in a glass vial containing 100 mg of tiotepa.
The pack contains 1 vial.

Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Importer
Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany
For further information about this medicine, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Tel.: +48 22 345 67 89

This medicinal product is authorised in the European Economic Area (EEA) Member States and in the United Kingdom (Northern Ireland) under the following names:

Information intended exclusively for healthcare professionals:

PREPARATION INSTRUCTIONS
Thiotepa Fresenius Kabi, 15 mg, powder for solution for concentrate for infusion
Thiotepa Fresenius Kabi, 100 mg, powder for solution for concentrate for infusion
Thiotepum

1. PRESENTATION

Thiotepa Fresenius Kabi (15 mg and 100 mg) is available as a powder for preparing a concentrate solution for infusion. Thiotepa Fresenius Kabi must be reconstituted and diluted immediately before administration.

2. SPECIAL PRECAUTIONS FOR DISPOSAL AND PREPARATION OF THE MEDICINAL PRODUCT FOR ADMINISTRATION

General information
Standard procedures for handling cytotoxic anticancer drugs must be followed. All transfer procedures must strictly adhere to aseptic techniques; the use of a laminar airflow cabinet with a fume hood is strongly recommended. As with other cytotoxic agents, care must be taken during the preparation and administration of thiotepa to avoid accidental contact with skin or mucous membranes. Accidental contact with thiotepa may cause local reactions. Protective gloves are recommended when preparing the infusion solution. If accidental contact with thiotepa solution occurs on the skin, wash immediately and thoroughly with soap and water. If accidental contact with thiotepa solution occurs on mucous membranes, rinse immediately and thoroughly with large amounts of water.

Dosing and administration in children, adolescents, and adults
Refer to section 4.2 of the Summary of Product Characteristics for guidance on dose calculation and administration of thiotepa in children, adolescents, and adults.

Reconstitution
Thiotepa Fresenius Kabi, 15 mg, powder for solution for concentrate for infusion
Thiotepa Fresenius Kabi should be dissolved in 1.5 mL of sterile water for injections.
Using a syringe fitted with a needle, aseptically withdraw 1.5 mL of sterile water for injections.

Thiotepa Fresenius Kabi, 100 mg, powder for solution for concentrate for infusion
Thiotepa Fresenius Kabi should be dissolved in 10 mL of sterile water for injections.
Using a syringe fitted with a needle, aseptically withdraw 10 mL of sterile water for injections.
Inject the contents of the syringe into the vial through the rubber stopper.
Remove the syringe and needle and mix thoroughly by repeated inversion.
Only clear solutions free from particulate matter should be used. The reconstituted solution may occasionally exhibit opalescence; such solutions may still be administered.

Further dilution in an infusion bag
The prepared solution is hypotonic and must be further diluted before administration in 500 mL of an infusion solution containing sodium chloride 9 mg/mL (0.9%) (1000 mL if the dose exceeds 500 mg), or in an appropriate volume of sodium chloride 9 mg/mL (0.9%) solution to achieve a final thiotepa concentration between 0.5 and 1 mg/mL.

Method of administration
Before administration, visually inspect the infusion solution for particulate matter. Discard solutions containing precipitate.
The infusion solution must be administered to patients using an infusion set equipped with a 0.2 μm filter. Filtration does not affect the potency of the solution.
Before each infusion and after completion of infusion, the indwelling catheter should be flushed with 5 mL of 0.9% sodium chloride solution (9 mg/mL) for injection.

Disposal
For single use only.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.