Prospect: 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 this prospect carefully before starting to use the medicine because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

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

Tiotepa Kabi is used to prepare the patient for a bone marrow transplant. It acts by destroyingthe bone marrow cells. In this way, it can receive a transplant of new bone marrow cells (hematopoietic stem cells), which in turn allow the body to produce healthy blood cells.

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

Do not use Tiotepa Kabi

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

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

Warnings and precautions

Inform your doctor if you have:

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

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

You will be given antibiotics for the prevention and treatment of infections.

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

Other medications and Tiotepa Kabi

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

Inform your doctor if you are pregnant or think you may be pregnant before receiving tiotepa. Do not use tiotepa during pregnancy.

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

After treatment is stopped, women should use effective contraceptive methods for at least 6 months and men for at least 3 months.

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

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

If you wish to have children after therapy, it is recommended to seek genetic counseling in advance.

Driving and operating machinery

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

Tiotepa Kabi contains sodium

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

The doctor will calculate the dose based on your body surface or weight and your condition.

How Tiotepa Kabi is administered

Tiotepa must be administered by a qualified healthcare professional through intravenous infusion (drip in a vein) after diluting each vial. Each infusion lasts 2-4 hours.

Administration frequency

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

Like all medicines, Tiotepa Kabi may cause side effects, although not everyone will experience them.

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

• Decrease in circulating blood cell counts (expected effect of the medication as preparation for transplant)
• Infection
• Liver problems, such as hepatic vein occlusion
• Transplant rejection (graft-versus-host disease)
• Respiratory complications

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

Tiotepa side effects occur with certain frequencies, which are defined as follows:

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

• Increased susceptibility to infections
• Generalized inflammation (septicemia)
• Decrease in white blood cell, platelet, and red blood cell counts (anemia)
• Transplant rejection (graft-versus-host disease)
• Dizziness, headache, blurred vision
• Uncontrolled body tremors (convulsions)
• Prickling, pins and needles sensation (paresthesia)
• Partial loss of mobility
• Cardiac arrest
• Nausea, vomiting, diarrhea
• Mucositis (inflammation of the oral mucosa)
• Gastrointestinal irritation
• Colon inflammation
• Anorexia, loss of appetite
• Elevated blood glucose
• Rash, itching, peeling
• Alteration of skin color (not to be confused with jaundice - see below)
• Redness of the skin (erythema)
• Hair loss
• Back and abdominal pain, pain
• Muscle and joint pain
• Abnormal heart electrical activity (arrhythmia)
• Pulmonary tissue inflammation
• Enlargement of the liver
• Altered function of some organs
• Hepatic vein occlusion (veno-occlusive disease, VOD)
• Yellowing of the skin and eyes (jaundice)
• Impaired hearing
• Lymphatic occlusion
• High blood pressure
• Enlargement of the liver, elevated renal and digestive enzymes
• Abnormal blood electrolyte levels
• Weight gain
• Fever, general weakness, chills
• Bleeding (hemorrhage)
• Nasal bleeding
• 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
• Delay in weight and height gain
• Urinary problems
• Inadequate testosterone production
• Inadequate thyroid hormone production
• Hypopituitarism
• Confusion state

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 incapacity
• Oxygen deficiency
• Pulmonary edema (fluid accumulation in the lungs)
• Pulmonary hemorrhage
• Respiratory arrest
• Blood in the urine (hematuria) and moderate renal insufficiency
• Urinary tract inflammation
• Difficulty urinating and decreased urine production (dysuria and oliguria)
• Elevated BUN (blood urea nitrogen) levels
• Cataracts
• Liver insufficiency
• Cerebral hemorrhage
• Cough
• Constipation and gastrointestinal discomfort
• Intestinal obstruction
• Stomach perforation
• Muscle tone changes
• General lack of coordination of muscle movements
• Bleeding associated with low platelet count
• Menopausal symptoms
• Cancer (main secondary neoplasms)
• Cerebral function alteration
• Male and female infertility

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

• Psoriasis erythrodérmica (skin inflammation and peeling)
• Delirium, nervousness, hallucinations, agitation
• Gastrointestinal ulcer
• Myocarditis (inflammation of the heart muscle)
• Abnormal heart disease (myocardialopathy)

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

• Increased blood pressure in the pulmonary arteries (pulmonary hypertension)
• Severe skin damage (e.g., severe lesions, bullae, etc.) that can affect the entire body surface, which can be even fatal
• Damage to a component of the brain (the so-called white matter) that can be even potentially fatal (leucoencephalopathy).

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use Tiotepa Kabi after the expiration date that appears on the packaging after "CAD".The expiration date is the last day of the month indicated.

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

After reconstitution, the medication remains stable for 8 hours when stored at2 °C-8 ºC.

After dilution, the medication remains stable for 24 hours when stored at 2 °C-8 °Cand for 4 hours when stored at 25 °C. From a microbiological standpoint, the productshould be used immediately. If not used immediately, the user will be responsible for the periods ofstorage during use and the storage conditions prior to use, which normally will not exceed 24 hours at 2-8 °C.

The disposal of unused medication and all materials that have come into contactwith it, will be carried out in accordance with local regulations.

Composition of Tiotepa Kabi

• The active principle 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, eachml contains 10 mg of tiotepa (10 mg/ml).
• Another excipient is sodium carbonate

Aspect of the product and contents of the package

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

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

Each box contains 1 vial.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Fresenius Kabi España, S.A.U.

Torre Mapfre – Vila Olímpica

Marina, 16-18.

08005 Barcelona (Spain)

Responsible for manufacturing

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Last review date of this leaflet:

07/2024

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS):http://www.aemps.gob.es/

This information is intended solely 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.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 before administration.

2.Special precautions for disposal and other manipulations

Generalities

Proper procedures for handling and disposing of anticancer drugs will be taken into account.All transfer procedures will have to comply strictly with aseptic techniques, preferably using a vertical laminar flow safety cabinet.As with other cytotoxic compounds, extreme caution will be exercised during the manipulation and preparation of tiotepa solutions to avoid accidental contact with the skin or mucous membranes.Accidental exposure to tiotepa may cause topical reactions. Therefore, the use of gloves is recommended during the preparation of the infusion solution.If tiotepa accidentally comes into contact with the skin, it should be washed immediately with water and soap.If tiotepa accidentally comes into contact with mucous membranes, they should be washed immediately with water.

Dosage calculation and posology in pediatric and adult patients

See section 4.2 of the technical data sheet for dosage 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 injection.

Using a syringe with a needle, withdraw 1.5 ml of sterile water for injection in 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 repeatedly inverting the vial.

Only colorless, transparent solutions without particles will be used. Reconstituted solutions may occasionally show opalescence; such solutions can still be administered.

Additional dilution in the infusion bag

The reconstituted solution is hypotonic and must be diluted before administration with 500 ml of injection solution with 9 mg/ml of sodium chloride (0.9%) for injections (1,000 ml if the dose is greater than 500 mg) or with an appropriate volume of 9 mg/ml sodium chloride (0.9%) to obtain 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 must be administered to patients using an infusion device equipped 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 must be washed with approximately 5 ml of injection solution with 9 mg/ml of sodium chloride (0.9%).

Disposal

Tiotepa Kabi is for single use only.

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