Thiotepa Riemsar 15 mg powder for concentrate for solution for infusion EFG
Spain
Table of Contents
- Package leaflet: Information for the user
- Introduction
- 1. What Thiotepa Riemser is and what it is used for
- 2. What you need to know before starting to use Thiotepa Riemser
- 3. How to use Thiotepa Riemser
- 4. Possible adverse effects
- 5. Storage of Thiotepa Riemser
- 6. Contents of the pack and other information
Package leaflet: Information for the user
Introduction
Package leaflet: information for the user
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser 100 mg powder for concentrate for solution for infusion EFG
tiotepa
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 further questions, ask your doctor.
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.
Contents of this leaflet
- What Thiotepa Riemser is and what it is used for
- What you need to know before using Thiotepa Riemser
- How to use Thiotepa Riemser
- Possible side effects
- How to store Thiotepa Riemser
- Contents of the pack and other information
1. What Thiotepa Riemser is and what it is used for
Thiotepa Riemser contains thiotepa as the active substance, a medicine belonging to the group of alkylating agents.
Thiotepa Riemser 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.
Thiotepa Riemser can be used in adults, children, and adolescents.
2. What you need to know before starting to use Thiotepa Riemser
Do not use Thiotepa Riemser
- 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, live viral vaccines, or bacterial vaccines.
Warnings and precautions
Tell 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 Thiotepa Riemser destroys bone marrow cells responsible for producing blood cells, you will need periodic blood tests during treatment to monitor your blood cell counts.
Antimicrobials will be administered for the prevention and treatment of infections.
Thiotepa Riemser may cause a different type of cancer in the future. Your doctor will explain this risk to you.
Other medicines and Thiotepa Riemser
Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.
Pregnancy, breastfeeding and fertility
Tell your doctor if you are pregnant or think you may be pregnant before starting Thiotepa Riemser. You must not use Thiotepa Riemser during pregnancy.
Both women and men receiving Thiotepa Riemser must use effective contraception during treatment. Men must not father a child while receiving treatment and for one year after completion of treatment.
It is unknown whether this medicine is excreted in human breast milk. As a precautionary measure, women must not breastfeed during treatment with Thiotepa Riemser.
Thiotepa Riemser may affect male and female fertility. Male patients should seek advice regarding sperm preservation before starting treatment.
Driving and using machines
Some adverse effects of thiotepa, 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.
3. How to use Thiotepa Riemser
Your doctor will calculate the dose based on your body surface area or body weight and your condition.
How Thiotepa Riemser is administered
Thiotepa Riemser 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 may cause adverse effects, although not everyone experiences them.
Some of the more serious adverse effects of treatment with Thiotepa Riemser or of the transplant procedure are:
- decrease in circulating blood cell counts (an expected effect of the medicine as part of preparation for your transplant infusion)
- infection
- liver problems, such as hepatic vein occlusion
- 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 manage these events.
Other adverse effects of Thiotepa Riemser, which may occur with certain frequencies, are listed 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
- 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, 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
- hepatic vein occlusion (veno-occlusive disease, VOD)
- yellowing of the skin and eyes (jaundice)
- hearing impairment
- lymphatic obstruction
- high blood pressure
- elevated liver, kidney, 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 one of the arteries in the brain (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 the 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 the blood
- 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 primary 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 the heart muscle tissue (myocarditis)
- abnormal heart disease (cardiomyopathy)
Frequency not known (frequency cannot be estimated from the 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 effects, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Thiotepa Riemser
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 after "CAD/EXP". The expiry date refers to the last day of the month indicated.
Store and transport refrigerated (between 2 °C and 8 °C).
Do not freeze.
After reconstitution, the medicine remains stable for 8 hours when stored between 2 °C and 8 °C.
After dilution, the medicine remains stable for 24 hours when stored between 2 °C and 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 should be disposed of in accordance with local regulations.
6. Contents of the pack and other information
Composition of Thiotepa Riemser
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
- The active substance is thiotepa. One vial contains 15 mg of thiotepa. After reconstitution, each ml contains 10 mg of thiotepa (10 mg/ml).
Thiotepa Riemser 100 mg powder for concentrate for solution for infusion EFG
- The active substance is thiotepa. One vial contains 100 mg of thiotepa. After reconstitution, each ml contains 10 mg of thiotepa (10 mg/ml).
- Thiotepa Riemser does not contain any other ingredients.
Appearance of the product and contents of the pack
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser is a white crystalline powder supplied in a glass vial containing 15 mg of thiotepa.
Thiotepa Riemser 100 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser is a white crystalline powder supplied in a glass vial containing 100 mg of thiotepa.
Each carton contains 1 vial.
Marketing Authorization Holder
Esteve Pharmaceuticals GmbH
Hohenzollerndamm 150-151
14199 Berlin
Germany
Manufacturer
HWI development GmbH
Straßburger Str. 77
77767 Appenweier
Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
Belgium/Belgium/Belgium Eurocept Pharmaceuticals Netherlands/Netherlands/Netherlands Tel/Tel: +31 35 528 8377 | Lithuania UAB ARMILA Lithuania Tel: +370- (0) 5 2777596 |
Bulgaria Thrive Pharma Ltd. Bulgaria Tel: +359 2 878 05 43 | Luxembourg/Luxembourg Eurocept Pharmaceuticals Netherlands/Netherlands/Netherlands Tél/Tel: +31 35 528 8377 |
Czech Republic LERAM pharmaceuticals s.r.o. Czech Republic Tel: +420 513 035 442 | Hungary SANATIS Europe Kft. Hungary Tel.: +36- (0) 23 367 673 |
Denmark CampusPharma AB Sweden Tlf: +46 31 205020 | Malta Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 |
Germany Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 | Netherlands Eurocept Pharmaceuticals Netherlands Tel: +31 35 528 8377 |
Estonia AUXILIA Pharma OÜ Estonia Tel: +372 605 00 05 | Norway CampusPharma AB Sweden Tlf: +46 31 205020 |
Greece Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 | Austria AGEA Pharma GmbH Austria Tel: +43- (0) 1 336 01 41 |
Spain Esteve Pharmaceuticals, S.A. Spain Tel: +34 93 446 60 00 | Poland COPHARMA JOSEPH RAKOTO Poland Tel.: +48 691 702 426 |
France KEOCYT France Tél: +33 1 42 31 07 10 | Portugal Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 |
Croatia MEDIS Adria d.o.o. Croatia Tel: +385 1 2303 446 | Romania SANATIS Europe Kft. Hungary Tel: +36- (0) 23 367 673 |
Ireland Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 | Slovenia MEDIS d.o.o. Slovenia Tel: +386- (0) 1 589 69 00 |
Iceland CampusPharma AB Iceland Tel: +46 31 205020 | Slovakia LERAM pharmaceuticals s.r.o. Czech Republic Tel: +420 513 035 442 |
Italy Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 | Finland CampusPharma AB Sweden Tel: +46 31 205020 |
Cyprus Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 | Sweden CampusPharma AB Sweden Tel: +46 31 205020 |
Latvia Auxilia Pharma OÜ Estonia Tel: +372 605 00 05 | United Kingdom (Northern Ireland) Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427-0 |
Date of the most recent review of this leaflet: {MM/YYYY}.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.
This information is intended for healthcare professionals only:
PREPARATION GUIDE
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser 100 mg powder for concentrate for solution for infusion EFG
thiotepa
Read this guide before preparing and administering Thiotepa Riemser.
- PRESENTATION
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser is supplied as 15 mg of powder for concentrate for solution for infusion.
Thiotepa Riemser 100 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser is supplied as 100 mg of powder for concentrate for solution for infusion.
Thiotepa Riemser 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 followed. All transfer procedures must strictly comply with 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 Thiotepa Riemser solutions to avoid accidental contact with skin or mucous membranes. Topical reactions may occur following accidental exposure to thiotepa. Therefore, the use of gloves is recommended during preparation of the infusion solution. If thiotepa solution comes into accidental contact with the skin, wash thoroughly with water and soap immediately. If thiotepa comes into accidental contact with mucous membranes, rinse thoroughly with water.
Dose Calculation of Thiotepa Riemser
Thiotepa Riemser 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 Thiotepa Riemser in adult and pediatric patients depends on the type of HSCT (autologous or allogeneic) and the disease.
Dosage in adults
AUTOLGOUS 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 agents, 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 agents, 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 agents, 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 agents, 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 agents, 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 agents, 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 agents, 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 agents, 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 to 2 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic agents, 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
AUTOLGOUS 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 agents, 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 agents, 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 agents, 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
Thiotepa Riemser 15 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser must be reconstituted with 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 Riemser 100 mg powder for concentrate for solution for infusion EFG
Thiotepa Riemser must be reconstituted with 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 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 show opalescence; such solutions may still be administered.
Further dilution in the infusion bag
The reconstituted solution is hypotonic and must be further diluted before administration with 500 ml of 9 mg/ml (0.9%) sodium chloride injection solution (1,000 ml if the dose exceeds 500 mg) or with an appropriate volume of 9 mg/ml (0.9%) sodium chloride solution to obtain a final concentration of Thiotepa Riemser between 0.5 and 1 mg/ml.
Administration
Thiotepa Riemser solution for infusion should be visually inspected for the presence of particles 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 alter the potency of the solution.
Thiotepa Riemser 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 (0.9%) sodium chloride injection solution.
Disposal
Thiotepa Riemser 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.