Thiotepa Vivanta 15 mg powder for concentrate for solution for infusion EFG
SpainTable of Contents
Patient Information Leaflet
Introduction
Patient Information Leaflet
Tiotepa Vivanta 15 mg powder for concentrate for solution for infusion EFG
tiotepa
Read this entire leaflet carefully before you start using this medicine, as 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 this leaflet:
- What Tiotepa Vivanta is and what it is used for
- What you need to know before using Tiotepa Vivanta
- How to use Tiotepa Vivanta
- Possible adverse effects
- How to store Tiotepa Vivanta
- 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 that belongs to the group of alkylating agents.
This medicine is used to prepare the patient 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 using Tiotepa Vivanta
Do not use Tiotepa Vivanta
- if you are allergic to thiotepa,
- if you are pregnant or think you might 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
Tell 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 to have regular blood tests during treatment to monitor your blood cell counts.
Antimicrobial agents will be administered for prevention and treatment of infections.
Tiotepa Vivanta may cause a different type of cancer in the future. Your doctor will explain this risk to you.
Other medicines and Tiotepa Vivanta
Tell 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 Vivanta. You must not use Tiotepa Vivanta during pregnancy.
Both women and men receiving Tiotepa Vivanta must use effective contraception during treatment.
Men must not father a child during treatment with Tiotepa Vivanta and for one year after the end of treatment.
It is unknown whether this medicine is excreted in human 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 or operate machinery. Do not drive or operate machinery if 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 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 preparation for your transplant)
- infection
- liver problems, such as blockage of a hepatic vein
- attack of the graft 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 Vivanta occur at certain frequencies, which are defined below:
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
- rash, pruritus, desquamation
- 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 hepatic vein (veno-occlusive disease, VOD)
- yellowing of the skin and eyes (jaundice)
- hearing deterioration
- 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
Common 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)
- altered 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 kidney failure
- inflammation of the urinary bladder
- discomfort when urinating and reduced urine output (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)
- altered 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 cardiac 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, blisters, etc.) that may affect the entire body surface, which can 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 packaging 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.
Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations.
6. Contents of the container and other information
Composition of Tiotepa Vivanta
- The active substance is tiotepa. One vial contains 15 mg of tiotepa. After reconstitution with 1.5 ml of water for injections, each ml contains 10 mg of tiotepa (10 mg/ml).
Tiotepa Vivanta contains no other components.
Appearance of the product and contents of the container
Tiotepa Vivanta is a white crystalline powder supplied in a 3 ml glass vial containing 15 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
You may request further information about this medicinal product by contacting 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 the most recent 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
This information is intended for healthcare professionals only:
PREPARATION GUIDE
Tiotepa Vivanta 15 mg powder for concentrate for solution for infusion
Tiotepa
Read this guide before preparing and administering Tiotepa Vivanta.
- PRESENTATION
Tiotepa Vivanta 15 mg powder for concentrate for solution for infusion
Tiotepa Vivanta must be reconstituted and diluted before administration.
- SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING
General
Appropriate procedures for handling and disposal of antineoplastic medicinal products 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 preparation of the infusion solution. If the tiotepa solution comes into accidental contact with the skin, wash thoroughly with soap and water immediately. If tiotepa comes into accidental contact with mucous membranes, rinse thoroughly with water.
Dose 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 between 125 mg/m²/day (3.38 mg/kg/day) and 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 the maximum cumulative total dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning treatment.
LYMPHOMA
The recommended dose ranges between 125 mg/m²/day (3.38 mg/kg/day) and 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 the 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 the maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning treatment.
MULTIPLE MYELOMA
The recommended dose ranges between 150 mg/m²/day (4.05 mg/kg/day) and 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 the 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 between 120 mg/m²/day (3.24 mg/kg/day) and 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 the maximum cumulative total dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning treatment.
BREAST CANCER
The recommended dose ranges between 120 mg/m²/day (3.24 mg/kg/day) and 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 the maximum cumulative total dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning treatment.
CNS TUMORS
The recommended dose ranges between 125 mg/m²/day (3.38 mg/kg/day) and 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 the 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 the maximum cumulative total dose of 500 mg/m² (13.51 mg/kg) throughout the conditioning treatment.
GERM CELL TUMORS
The recommended dose ranges between 150 mg/m²/day (4.05 mg/kg/day) and 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 the 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 between 185 mg/m²/day (5 mg/kg/day) and 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 the 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 the 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 the maximum cumulative total dose of 185 mg/m² (5 mg/kg) throughout the conditioning treatment.
LEUKEMIA
The recommended dose ranges between 185 mg/m²/day (5 mg/kg/day) and 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 the 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 the 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 between 150 mg/m²/day (6 mg/kg/day) and 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 the maximum cumulative total dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning treatment.
CNS TUMORS
The recommended dose ranges between 250 mg/m²/day (10 mg/kg/day) and 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 the 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 between 125 mg/m²/day (5 mg/kg/day) and 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 the 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 the maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.
THALASSEMIA
The recommended dose ranges between 200 mg/m²/day (8 mg/kg/day) and 250 mg/m²/day (10 mg/kg/day), divided into two daily infusions administered prior to allogeneic HSCT without exceeding the 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 the 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 the 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 the maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning treatment.
Reconstitution
Tiotepa Vivanta 15 mg powder for concentrate for solution for infusion
Tiotepa Vivanta must be reconstituted with 1.5 ml of sterile water for injections.
Using a syringe fitted with a needle, withdraw 1.5 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 injection solution (0.9%) for injections (1,000 ml if the dose exceeds 500 mg) or with an appropriate volume of 9 mg/ml sodium chloride (0.9%) for injection to achieve a final concentration of Tiotepa Vivanta between 0.5 and 1 mg/ml.
Administration
Tiotepa Vivanta solution for infusion 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 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 by infusion over 2–4 hours at room temperature (approximately 25 °C) and under normal lighting conditions.
The indwelling catheter should be flushed before and after each infusion with approximately 5 ml of 9 mg/ml sodium chloride injection solution (0.9%).
Disposal
Tiotepa Vivanta is for single use only.
Any unused medicinal product and all materials that have been in contact with it must be disposed of in accordance with local regulations.