Thiotepa Vivanta 100 mg powder for concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

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

tiotepa

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

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

Contents of the leaflet:

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

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

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

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

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

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

Do not use Tiotepa Vivanta

• if you are allergic to thiotepa,
• if you are pregnant or think you may be pregnant,
• if you are breastfeeding,
• 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 epilepsy, or have had them in the past (if you have been treated with phenytoin or fosphenytoin).

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

Antimicrobial agents will be administered for the prevention and treatment of infections.

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

Other medicines and Tiotepa Vivanta

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 may be pregnant before receiving Tiotepa Vivanta. You must not use Tiotepa Vivanta during pregnancy.

Both women and men receiving Tiotepa Vivanta should use effective contraceptive methods during treatment.

Men must not father a child during treatment with Tiotepa Vivanta and for one year after treatment has ended.

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

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

Driving and using machines

Some adverse reactions of thiotepa, such as dizziness, headache and blurred vision, may affect your ability to drive and operate machinery. Do not drive or operate machinery if you are affected.

3. How to use Tiotepa Vivanta

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

How Tiotepa Vivanta is administered

Tiotepa Vivanta 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. The treatment may last up to 5 days. The frequency of administration and the duration of treatment will depend on your condition.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

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

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

The adverse effects of Tiotepa Vivanta 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 counts of white blood cells, platelets, and red blood cells (anemia)
• attack by transplanted cells against your body (graft-versus-host disease)
• dizziness, headache, blurred vision
• uncontrollable 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)
• skin redness (erythema)
• hair loss
• back and abdominal pain, pain
• muscle and joint pain
• abnormal electrical activity in the heart (arrhythmia)
• inflammation of lung tissue
• liver enlargement
• impaired function of certain organs
• hepatic vein occlusion (veno-occlusive disease, VOD)
• yellowing of the skin and eyes (jaundice)
• hearing deterioration
• lymphatic obstruction
• high blood pressure
• liver enlargement, increased 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 gain and growth
• bladder problems
• insufficient testosterone production
• insufficient thyroid hormone production
• reduced pituitary activity
• confusion

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

• anxiety, confusion
• abnormal dilation of a brain artery (intracranial aneurysm)
• elevated creatinine levels
• allergic reactions
• blockage of a blood vessel (embolism)
• irregular heart rhythm
• heart failure
• cardiovascular insufficiency
• oxygen deficiency
• fluid accumulation in the lungs (pulmonary edema)
• pulmonary hemorrhage
• respiratory arrest
• blood in urine (hematuria) and moderate renal failure
• inflammation of the urinary bladder
• discomfort during urination and reduced urine output (dysuria and oliguria)
• increased levels of nitrogen-containing components in 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 in muscular movements
• bruising associated with low platelet count
• menopausal symptoms
• cancer (secondary malignant neoplasms)
• impaired brain function
• male and female infertility

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

• skin inflammation and peeling (erythrodermic psoriasis)
• delirium, nervousness, hallucinations, agitation
• gastrointestinal ulcer
• inflammation of 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 adverse effect, consult your doctor or pharmacist, 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 Vivanta

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

Do not use Tiotepa Vivanta 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 medicinal product remains stable for 8 hours when stored at 2°C-8 °C.

After dilution, the medicinal product 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.

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

6. Contents of the container and additional information

Composition of Tiotepa Vivanta

• The active substance is tiotepa. One vial contains 100 mg of tiotepa. After reconstitution with 10 ml of water for injections, each ml contains 10 mg of tiotepa (10 mg/ml).

Tiotepa Vivanta does not contain any other components.

Appearance of the product and contents of the container

Tiotepa Vivanta is a white crystalline powder supplied in a 10 ml glass vial containing 100 mg of tiotepa.

Each carton contains 1 vial.

Marketing Authorization Holder

Vivanta Generics s.r.o.

Trtinová 260/1, Cakovice

196 00 Prague 9

Czech Republic

Manufacturer

Pharmadox Healthcare Ltd.,

KW20A Corradino Industrial Estate

Paola PLA3000, Malta

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Local Representative:

Vivanta Generics s.r.o. Spanish branch

C/Guzmán el Bueno, 133, edificio Britannia

28003 Madrid, Spain

Date of latest revision of this leaflet: May 2025

Detailed and up-to-date 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

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This information is intended for healthcare professionals only:

PREPARATION GUIDE

Tiotepa Vivanta 100 mg powder for concentrate for solution for infusion

Tiotepa

Read this guide before preparing and administering Tiotepa Vivanta.

1. PRESENTATION

Tiotepa Vivanta 100 mg powder for concentrate for solution for infusion

Tiotepa Vivanta must be reconstituted and diluted before 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 should be exercised during handling and preparation of Tiotepa Vivanta 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 during the preparation of the infusion solution. If the tiotepa solution comes into accidental contact with the skin, wash thoroughly with water and soap immediately. If tiotepa comes into accidental contact with mucous membranes, rinse thoroughly with water.

Dosage calculation of Tiotepa Vivanta

Tiotepa Vivanta is administered at various doses and in combination with other chemotherapeutic agents to patients undergoing conventional hematopoietic stem cell transplantation (HSCT) due to hematological diseases or solid tumors. The recommended dosage of tiotepa in adult and pediatric patients depends on the type of HSCT (autologous or allogeneic) and the disease.

Dosage in adults

AUTologous HSCT

Hematological diseases

The recommended dose in hematological diseases ranges from 125 mg/m²/day (3.38 mg/kg/day) to 300 mg/m²/day (8.10 mg/kg/day) as a single daily infusion administered for 2 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning treatment.

LYMPHOMA

The recommended dose ranges from 125 mg/m²/day (3.38 mg/kg/day) to 300 mg/m²/day (8.10 mg/kg/day) as a single daily infusion administered for 2 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning treatment.

CENTRAL NERVOUS SYSTEM (CNS) LYMPHOMA

The recommended dose is 185 mg/m²/day (5 mg/kg/day) as a single daily infusion administered for 2 consecutive days prior to autologous HSCT, without exceeding a maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning treatment.

MULTIPLE MYELOMA

The recommended dose ranges from 150 mg/m²/day (4.05 mg/kg/day) to 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning treatment.

Solid tumors

The recommended dose in solid tumors ranges from 120 mg/m²/day (3.24 mg/kg/day) to 250 mg/m²/day (6.76 mg/kg/day), divided into one or two daily infusions administered for 2 to 5 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning treatment.

BREAST CANCER

The recommended dose ranges from 120 mg/m²/day (3.24 mg/kg/day) to 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 to 5 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning treatment.

CNS TUMORS

The recommended dose ranges from 125 mg/m²/day (3.38 mg/kg/day) to 250 mg/m²/day (6.76 mg/kg/day), divided into one or two daily infusions administered for 3 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning treatment.

OVARIAN CANCER

The recommended dose is 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 2 consecutive days prior to autologous HSCT, without exceeding a maximum cumulative total dose of 500 mg/m² (13.51 mg/kg) throughout the conditioning treatment.

GERM CELL TUMORS

The recommended dose ranges from 150 mg/m²/day (4.05 mg/kg/day) to 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning treatment.

ALLOGENEIC HSCT

Hematological diseases

The recommended dose in hematological diseases ranges from 185 mg/m²/day (5 mg/kg/day) to 481 mg/m²/day (13 mg/kg/day), divided into one or two daily infusions administered for 1 to 3 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 555 mg/m² (15 mg/kg) throughout the conditioning treatment.

LYMPHOMA

The recommended dose is 370 mg/m²/day (10 mg/kg/day) divided into two daily infusions prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning treatment.

MULTIPLE MYELOMA

The recommended dose is 185 mg/m²/day (5 mg/kg/day) as a single daily infusion prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 185 mg/m² (5 mg/kg) throughout the conditioning treatment.

LEUKEMIA

The recommended dose ranges from 185 mg/m²/day (5 mg/kg/day) to 481 mg/m²/day (13 mg/kg/day), divided into one or two daily infusions administered for 1 or 2 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 555 mg/m² (15 mg/kg) throughout the conditioning treatment.

THALASSEMIA

The recommended dose is 370 mg/m²/day (10 mg/kg/day) divided into two daily infusions administered prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning treatment.

Dosage in pediatric patients

AUTologous HSCT

Solid tumors

The recommended dose in solid tumors ranges from 150 mg/m²/day (6 mg/kg/day) to 350 mg/m²/day (14 mg/kg/day) as a single daily infusion administered for 2 to 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning treatment.

CNS TUMORS

The recommended dose ranges from 250 mg/m²/day (10 mg/kg/day) to 350 mg/m²/day (14 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning treatment.

ALLOGENEIC HSCT

Hematological diseases

The recommended dose in hematological diseases ranges from 125 mg/m²/day (5 mg/kg/day) to 250 mg/m²/day (10 mg/kg/day), divided into one or two daily infusions administered for 1 to 3 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 375 mg/m² (15 mg/kg) throughout the conditioning treatment.

LEUKEMIA

The recommended dose is 250 mg/m²/day (10 mg/kg/day) divided into two daily infusions administered prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.

THALASSEMIA

The recommended dose ranges from 200 mg/m²/day (8 mg/kg/day) to 250 mg/m²/day (10 mg/kg/day), divided into two daily infusions administered prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.

REFRACTORY CYTOPENIA

The recommended dose is 125 mg/m²/day (5 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 375 mg/m² (15 mg/kg) throughout the conditioning treatment.

GENETIC DISEASES

The recommended dose is 125 mg/m²/day (5 mg/kg/day) as a single daily infusion administered for 2 consecutive days prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.

SICKLE CELL ANEMIA

The recommended dose is 250 mg/m²/day (10 mg/kg/day) divided into two daily infusions administered prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.

Reconstitution

Tiotepa Vivanta 100 mg powder for concentrate for solution for infusion

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

Using a syringe fitted 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 without particles should be used. Reconstituted solutions may occasionally show opalescence; such solutions may still be administered.

Further dilution in the infusion bag

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

Administration

Tiotepa Vivanta solution for infusion should be visually inspected for the presence of particles before 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 alter the potency of the solution.

Tiotepa Vivanta must be administered under aseptic conditions as an infusion over 2–4 hours at room temperature (approximately 25 °C) and under normal lighting conditions.

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

Disposal

Tiotepa Vivanta is for single use only.

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