Tepadina
thiotepa
thiotepa
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.
What TEPADINA is and what it is used for
What you need to know before you use TEPADINA
How to use TEPADINA
Possible side effects
How to store TEPADINA
Contents of the pack and other information
TEPADINA contains the active substance thiotepa, which belongs to a group of medicines called alkylating agents.
TEPADINA is used to prepare patients for bone marrow transplantation. It works by destroying bone marrow cells. This enables the transplantation of new bone marrow cells (haematopoietic progenitor cells), which in turn enable the body to produce healthy blood cells.
TEPADINA can be used in adults and children and adolescents.
if you are allergic to thiotepa,
if you are pregnant or think you may be pregnant,
if you are breast-feeding,
if you are receiving yellow fever vaccination, live virus and bacterial vaccines.
You should tell your doctor if you have:
liver or kidney problems,
heart or lung problems,
seizures/fits (epilepsy) or have had them in the past (if treated with phenytoin or fosphenytoin).
Because TEPADINA destroys bone marrow cells responsible for producing blood cells, regular blood tests will be taken during treatment to check your blood cell counts.
In order to prevent and manage infections, you will be given anti-infectives.
TEPADINA may cause another type of cancer in the future. Your doctor will discuss this risk with you.
Tell your doctor if you are taking, have recently taken or might take any other medicines.
You must tell your doctor if you are pregnant or you think you may be pregnant before you receive TEPADINA. You must not use TEPADINA during pregnancy.
Both women and men using TEPADINA must use effective contraceptive methods during treatment. Men should not father a child while treated with TEPADINA and during the year after cessation of treatment.
It is not known whether this medicinal product is excreted in breast milk. As a precautionary measure, women must not breast-feed during treatment with TEPADINA.
TEPADINA can impair male and female fertility. Male patients should seek advice for sperm preservation before therapy is started.
It is likely that certain adverse reactions of thiotepa like dizziness, headache and blurred vision could affect your ability to drive and use machines. If you are affected, do not drive or use machines.
Your doctor will calculate the dose according to your body surface or weight and your disease.
TEPADINA is administered by a qualified healthcare professional as an intravenous infusion (drip in a vein) after dilution of the individual vial. Each infusion will last 2-4 hours.
You will receive your infusions every 12 or 24 hours. The duration of treatment can last up to 5 days. Frequency of administration and duration of treatment depend on your disease.
Like all medicines, TEPADINA can cause side effects, although not everybody gets them. The most serious side effects of TEPADINA therapy or the transplant procedure may include
decrease in circulating blood cell counts (intended effect of the medicine to prepare you for your transplant infusion)
infection
liver disorders including blocking of a liver vein
the graft attacks your body (graft versus host disease)
respiratory complications
Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events.
Side effects of TEPADINA may occur with certain frequencies, which are defined as follows:
increased susceptibility to infection
whole-body inflammatory state (sepsis)
decreased counts of white blood cells, platelets and red blood cells (anaemia)
the transplanted cells attack your body (graft versus host disease)
dizziness, headache, blurred vision
uncontrolled shaking of the body (convulsion)
sensation of tingling, pricking or numbness (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mucosa of the mouth (mucositis)
irritated stomach, gullet, intestine
inflammation of the colon
anorexia, decreased appetite
high glucose in the blood
skin rash, itching, shedding
skin colour disorder (do not confuse 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
altered organ function
blocking of a liver vein (veno-occlusive disease, VOD)
yellowing of the skin and eyes (jaundice)
hearing impaired
lymphatic obstruction
high blood pressure
increased liver, renal and digestive enzymes
abnormal blood electrolytes
weight gain
fever, general weakness, chills
bleeding (haemorrhage)
nasal bleeding
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
decreased sperm cell count
vaginal bleeding
absence of menstrual periods (amenorrhea)
memory loss
delaying in weight and height increase
bladder disfunction
underproduction of testosterone
insufficient production of thyroid hormone
deficient activity of the pituitary gland
confusional state
anxiety, confusion
abnormal bulging outward of one of the arteries in the brain (intracranial aneurysm)
creatinine elevated
allergic reactions
occlusion of a blood vessel (embolism)
heart rhythm disorder
heart inability
cardiovascular inability
oxygen deficiency
fluid accumulation in the lungs (pulmonary oedema)
pulmonary bleeding
respiratory arrest
blood in the urine (haematuria) and moderate renal insufficiency
inflammation of the urinary bladder
discomfort in urination and decrease in urine output (disuria and oliguria)
increase in the amount of nitrogen components in the blood stream (BUN increase)
cataract
inability of the liver
cerebral haemorrhage
cough
constipation and upset stomach
obstruction of the bowel
perforation of stomach
changes in muscle tone
gross lack of coordination of muscle movements
bruises due to a low platelet count
menopausal symptoms
cancer (second primary malignancies)
abnormal brain function
male and female infertility
inflammation and exfoliation of the skin (erythrodermic psoriasis)
delirium, nervousness, hallucination, agitation
gastrointestinal ulcer
inflammation of the muscular tissue of the heart (myocarditis)
abnormal heart condition (cardiomyopathy)
increased blood pressure in the arteries (blood vessels) of the lungs (pulmonary arterial hypertension)
severe skin damage (e.g. severe lesions, bullae, etc.) potentially involving the full body surface which can be even life-threatening
damage to a component of the brain (the so-called white matter) which can be even life- threatening (leukoencephalopathy).
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this
medicine.
Keep this medicine out of the sight and reach of children.
Do not use TEPADINA after the expiry date which is stated on the carton and vial label, after EXP. The expiry date refers to the last day of that month.
Store and transport refrigerated (2°C-8°C). Do not freeze.
After reconstitution the product is stable for 8 hours when stored at 2°C -8°C.
After dilution the product 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 product should be used immediately.
Any unused product or waste material should be disposed of in accordance with local requirements.
The active substance is thiotepa. One vial contains 15 mg thiotepa. After reconstitution, each mL contains 10 mg thiotepa (10 mg/mL).
TEPADINA does not contain any other ingredients.
TEPADINA is a white crystalline powder supplied in a glass vial containing 15 mg thiotepa. Each carton contains 1 vial.
ADIENNE S.r.l. S.U.
Via Galileo Galilei, 19 20867 Caponago (MB) Italy Tel: +39 02 40700445
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Accord Healthcare AB Tel: +46 8 624 00 25
Accord Healthcare Polska Sp. z o.o.
Teл.: +48 22 577 28 00
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 00
Accord Healthcare Polska Sp. z o.o. Tel.: +48 22 577 28 00
Accord Healthcare AB Tlf: + 46 8 624 00 25
Accord Healthcare Ireland Ltd Tel: +44 (0) 208 901 3370
Accord Healthcare GmbH Tel: +49 89 700 9951 0
Accord Healthcare B.V. Tel: +31 30 850 6014
Accord Healthcare AB Tel: +46 8 624 00 25
Accord Healthcare AB Tlf: + 46 8 624 00 25
Accord Healthcare Italia Srl
Τηλ: + 39 02 943 23 700
Accord Healthcare GmbH Tel: +43 (0)662 424899-0
Accord Healthcare S.L.U. Tel: +34 93 301 00 64
Accord Healthcare Polska Sp. z o.o. Tel.: +48 22 577 28 00
Accord Healthcare France SAS
Tél: +33 (0)320 401 770
Accord Healthcare, Unipessoal Lda Tel: +351 214 697 835
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 00
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 00
Accord Healthcare Ireland Ltd Tel: +44 (0)1271 385257
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 00
Accord Healthcare AB Sími: + 46 8 624 00 25
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 00
Accord Healthcare Italia Srl Tel: +39 02 943 23 700
Accord Healthcare Oy Puh/Tel: + 358 10 231 4180
Accord Healthcare S.L.U.
Τηλ: + 34 93 301 00 64
Accord Healthcare AB Tel: + 46 8 624 00 25
Accord Healthcare AB
Tel: +46 8 624 00 25
Accord-UK Ltd
Tel: +44 (0)1271 385257
The following information is intended for healthcare professionals only.
Thiotepa
Read this guide prior to the preparation and administration of TEPADINA.
TEPADINA is supplied as 15 mg powder for concentrate for solution for infusion. TEPADINA must be reconstituted and diluted prior to administration.
General
Procedures for proper handling and disposal of anticancer medicinal products should be considered. All transfer procedures require strict adherence to aseptic techniques, preferably employing a vertical laminar flow safety hood.
As with other cytotoxic compounds, caution need to be exercised in handling and preparation of TEPADINA solutions to avoid accidental contact with skin or mucous membranes. Topical reactions associated with accidental exposure to thiotepa may occur. In fact, the use of gloves is recommended in preparing the solution for infusion. If thiotepa solution accidentally contacts the skin, immediately the skin must be thoroughly washed with soap and water. If thiotepa accidentally contacts mucous membranes, they must be flushed thoroughly with water.
Calculation of dose of TEPADINA
TEPADINA is administered at different doses in combination with other chemotherapeutic medicinal products in patients prior to conventional haematopoietic progenitor cell transplantation (HPCT) for haematological diseases or solid tumours.
TEPADINA posology is reported, in adult and paediatric patients, according to the type of HPCT (autologous or allogeneic) and disease.
Posology in adults
AUTOLOGOUS HPCT
The recommended dose in haematological 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 from 2 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 900 mg/m2 (24.32 mg/kg), during the time of the entire 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 from 2 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 900 mg/m2 (24.32 mg/kg), during the time of the entire 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 before autologous HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/kg), during the time of the entire 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 before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
The recommended dose in solid tumours ranges from 120 mg/m2/day (3.24 mg/kg/day) to
250 mg/m2/day (6.76 mg/kg/day) divided in one or two daily infusions, administered from 2 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of
800 mg/m2 (21.62 mg/kg), during the time of the entire 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 from 3 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 800 mg/m2 (21.62 mg/kg), during the time of the entire conditioning treatment.
CNS TUMOURS
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 in one or two daily infusions, administered from 3 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
OVARIAN CANCER
The recommended dose is 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered in 2 consecutive days before autologous HPCT, without exceeding the total maximum cumulative dose
of 500 mg/m2 (13.51 mg/kg), during the time of the entire conditioning treatment.
GERM CELL TUMOURS
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 before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
ALLOGENEIC HPCT
The recommended dose in haematological diseases ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 3 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
LYMPHOMA
The recommended dose in lymphoma is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2
(10 mg/kg), during the time of the entire conditioning treatment. MULTIPLE MYELOMA
The recommended dose is 185 mg/m2/day (5 mg/kg/day) as a single daily infusion before allogeneic
HPCT, without exceeding the total maximum cumulative dose of 185 mg/m2 (5 mg/kg), during the time of the entire conditioning treatment.
LEUKAEMIA
The recommended dose ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day
(13 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 2 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
THALASSEMIA
The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2
(10 mg/kg), during the time of the entire conditioning treatment.
Posology in paediatric patients
AUTOLOGOUS HPCT
The recommended dose in solid tumours 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 from 2 up to 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 1 050 mg/m2 (42 mg/kg), during the time of the entire conditioning treatment.
CNS TUMOURS
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 before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 1 050 mg/m2 (42 mg/kg), during the time of the entire conditioning treatment.
ALLOGENEIC HPCT
The recommended dose in haematological diseases ranges from 125 mg/m2/day (5 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 3 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 375 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
LEUKAEMIA
The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2
(10 mg/kg), during the time of the entire 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 in two daily infusions, administered before allogeneic HPCT without exceeding the total
maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire 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 before allogeneic HPCT, without exceeding the total maximum cumulative dose of 375 mg/m2 (15 mg/kg), during the time of the entire 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 before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.
SICKLE CELL ANAEMIA
The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2
(10 mg/kg), during the time of the entire conditioning treatment.
Reconstitution
TEPADINA 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. Inject the content of the syringe into the vial through the rubber stopper.
Remove the syringe and the needle and mix manually by repeated inversions.
Only colourless solutions, without any particulate matter, must be used. Reconstituted solutions may occasionally show opalescence; such solutions can still be administered.
Further dilution in the infusion bag
The reconstituted solution is hypotonic and must be further diluted prior to administration with
500 mL sodium chloride 9 mg/mL (0.9%) solution for injection (1 000 mL if the dose is higher than 500 mg) or with an appropriate volume of sodium chloride 9 mg/mL (0.9%) in order to obtain a final TEPADINA concentration between 0.5 and 1 mg/mL.
Administration
TEPADINA infusion solution should be inspected visually for particulate matter prior to administration. Solutions containing a precipitate should be discarded.
The infusion solution must be administered to patients using an infusion set equipped with a 0.2 µm in-line filter. Filtering does not alter solution potency.
TEPADINA should be aseptically administered as a 2-4 hours infusion under room temperature (about 25°C) and normal light conditions.
Prior to and following each infusion, the indwelling catheter line should be flushed with approximately 5 mL sodium chloride 9 mg/mL (0.9%) solution for injection.
Disposal
TEPADINA is for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements