Tepadina: detailed information

Package leaflet: Information for the user

TEPADINA 15 mg powder for concentrate for solution for infusion

tiotepa
Please 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 questions, ask your doctor.
If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

What TEPADINA is and what it is used for
What you need to know before using TEPADINA
How to use TEPADINA
Possible side effects
How to store TEPADINA
Contents of the pack and other information

1. What TEPADINA is and what it is used for

TEPADINA contains the active substance tiotepa, 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 allows 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, children, and adolescents.

2. What you need to know before using TEPADINA

Do not use TEPADINA

if you are allergic to thiotepa,
if you are pregnant or suspect you might be pregnant,
if you are breastfeeding,
if you are receiving the yellow fever vaccine, live virus vaccines or bacterial vaccines.

Warnings and precautions
Tell your doctor if you have:

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

Since TEPADINA destroys bone marrow cells responsible for blood cell production,
you will have regular blood tests during treatment to monitor your blood cell counts.
To prevent and treat infections, you will be given anti-infective agents.
TEPADINA may cause another type of tumour in the future. Your doctor will discuss this
risk with you.
Other medicines and TEPADINA
Tell your doctor if you are taking, have recently taken, or might take any other
medicines.
Pregnancy, breastfeeding and fertility
Before taking TEPADINA, inform your doctor if you are pregnant or think you might be pregnant. Do not use TEPADINA during pregnancy.
During treatment with TEPADINA, both men and women must use effective contraception. Men must not father a child during treatment with TEPADINA and for one year after stopping treatment.
It is not known whether this medicine is excreted in human milk. As a precautionary measure, women must not breastfeed during treatment with TEPADINA.
TEPADINA may impair male and female fertility. Male patients are advised to consider sperm preservation before starting therapy.
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. If you experience these symptoms, do not drive
and do not use machinery.

3. How to use TEPADINA

The doctor will calculate the dosage according to body surface area or body weight, and depending on the disease.
How TEPADINA is administered
TEPADINA is administered by a qualified healthcare professional as an intravenous infusion (a drip into a vein) after dilution of the single vial. Each infusion will last 2–4 hours.
Frequency of administration
Infusions will be given every 12 or 24 hours. Treatment may last up to 5 days. The frequency of administration and duration of treatment depend on the disease.

4. Possible side effects

Like all medicines, TEPADINA can cause side effects, although not everybody gets them.
The most serious side effects of TEPADINA therapy or of the transplant procedure include:

reduction in circulating blood cell counts (an intended effect of the medicine to prepare you for transplant infusion)
infection
liver disorders, including blockage of a liver vein
the transplanted cells attack the body (graft-versus-host disease)
respiratory complications
Your doctor will regularly monitor your blood cell counts and liver enzymes to detect and manage these events.

Side effects with TEPADINA may occur with varying frequencies, defined as follows:

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

increased susceptibility to infections
systemic inflammatory condition affecting the whole body (sepsis)
reduced counts of white blood cells, platelets, and red blood cells (anaemia)
transplanted cells attacking the body (graft-versus-host disease)
dizziness, headache, blurred vision
uncontrolled body shaking (seizures)
tingling, prickling, and numbness sensation (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mucous lining of the mouth (mucositis)
irritation of the stomach, oesophagus, and intestine
inflammation of the colon
anorexia, loss of appetite
high blood glucose levels
skin rash, itching, peeling
change in skin colour (do not confuse with jaundice – see below)
redness of the skin (erythema)
hair loss
abdominal and back pain, general pain
muscle and joint pain
abnormal electrical activity of the heart (arrhythmia)
inflammation of lung tissue
enlarged liver
altered organ function
blockage of a liver vein (VOD – veno-occlusive disease)
yellowing of the skin and eyes (jaundice)
hearing loss
lymphatic obstruction
high blood pressure
increased liver, renal, and digestive enzymes
abnormal blood electrolytes
weight gain
fever, weakness, chills
bleeding (haemorrhage)
nosebleed
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
reduced sperm count
vaginal bleeding
absence of menstrual periods (amenorrhoea)
memory loss
delayed increase in weight and height growth
bladder dysfunction
reduced testosterone production
insufficient production of thyroid hormones
reduced pituitary gland activity
confusion

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

anxiety, confusion
abnormal outward bulging of one of the brain arteries (intracranial aneurysm)
elevated creatinine
allergic reactions
blockage of a blood vessel (embolism)
heart rhythm disorders
altered cardiac function
altered cardiovascular function
oxygen deficiency
fluid accumulation in the lungs (pulmonary oedema)
lung bleeding
respiratory arrest
blood in the urine (haematuria) and moderate kidney failure
inflammation of the urinary bladder
difficulty urinating and reduced urine output (dysuria and oliguria)
increased levels of nitrogen-containing compounds in the blood (increased BUN)
cataract
altered liver function
cerebral haemorrhage
cough
constipation and stomach disturbances
intestinal obstruction
stomach perforation
altered muscle tone
lack of coordination in muscle movements
bruising due to low platelet count
menopausal symptoms
cancer (secondary primary tumour)
abnormal brain function
male and female infertility

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

skin inflammation and peeling (erythrodermic psoriasis)
delirium, nervousness, hallucinations, agitation
gastrointestinal ulcer
inflammation of myocardial tissue (myocarditis)
abnormal heart conditions (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 and may also be life-threatening.
damage to a component of the brain (so-called white matter) that may also be life-threatening (leukoencephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TEPADINA

Keep this medicine out of the sight and reach of children.
Do not use TEPADINA after the expiry date stated on the carton and vial label, after EXP. The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C-8 °C).
Do not freeze.
After reconstitution, the product is stable for 80 hours when stored at 2 °C - 8 °C.
After dilution, the product is stable for up to 48 hours when stored at 2°C - 8°C and up to 6 hours when stored at 25°C.
From a microbiological standpoint, the product should be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What TEPADINA contains

The active substance is thiotepa. One vial contains 15 mg of thiotepa. After reconstitution, each mL contains 10 mg of thiotepa (10 mg/mL).
TEPADINA contains no other ingredients.

Description of the appearance of TEPADINA and contents of the pack
TEPADINA is a white crystalline powder contained in a glass vial; each vial contains 15 mg of thiotepa.
Each carton contains one vial.

Marketing Authorisation Holder and Manufacturer
ADIENNE S.r.l. S.U.
Via Galileo Galilei, 19
20867 Caponago (MB), Italy
Tel: +39-02 40700445
[email protected]

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Accord Healthcare bv Accord Healthcare AB
Tél/Tel: +32 51 79 40 12 Tel: +46 8 624 00 25

България Luxembourg/Luxemburg
Accord Healthcare Polska Sp. z o.o. Accord Healthcare bv
Tel.: +48 22 577 28 00 Tél/Tel: +32 51 79 40 12

Česká republika Magyarország
Accord Healthcare Polska Sp. z o.o. Accord Healthcare Polska Sp. z o.o.
Tel: +48 22 577 28 00 Tel.: +48 22 577 28 00

Danmark Malta
Accord Healthcare AB Accord Healthcare Ireland Ltd
Tlf: +46 8 624 00 25 Tel: +44 (0) 208 901 3370

Deutschland Nederland
Accord Healthcare GmbH Accord Healthcare B.V.
Tel: +49 89 700 9951 0 Tel: +31 30 850 6014

Eesti Norge
Accord Healthcare AB Accord Healthcare AB
Tel: +46 8 624 00 25 Tlf: +46 8 624 00 25

Ελλάδα Österreich
Accord Healthcare Italia Srl Accord Healthcare GmbH
Τηλ: +39 02 943 23 700 Tel: +43 (0)662 424899-0

España Polska
Accord Healthcare S.L.U. Accord Healthcare Polska Sp. z o.o.
Tel: +34 93 301 00 64 Tel.: +48 22 577 28 00

France Portugal
Accord Healthcare France SAS Accord Healthcare, Unipessoal Lda
Tél: +33 (0)320 401 770 Tel: +351 214 697 835

Hrvatska România
Accord Healthcare Polska Sp. z o.o. Accord Healthcare Polska Sp. z o.o.
Tel: +48 22 577 28 00 Tel: +48 22 577 28 00

Ireland Slovenija
Accord Healthcare Ireland Ltd Accord Healthcare Polska Sp. z o.o.
Tel: +44 (0)1271 385257 Tel: +48 22 577 28 00

Ísland Slovenská republika
Accord Healthcare AB Accord Healthcare Polska Sp. z o.o.
Sími: +46 8 624 00 25 Tel: +48 22 577 28 00

Italia Suomi/Finland
Accord Healthcare Italia Srl Accord Healthcare Oy
Tel: +39 02 943 23 700 Puh/Tel: +358 10 231 4180

Κύπρος Sverige
Accord Healthcare S.L.U. Accord Healthcare AB
Τηλ: +34 93 301 00 64 Tel: +46 8 624 00 25

Latvija United Kingdom (Northern Ireland)
Accord Healthcare AB Accord-UK Ltd
Tel: +46 8 624 00 25 Tel: +44 (0)1271 385257

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only.

INSTRUCTIONS FOR PREPARATION
TEPADINA 15 mg powder for concentrate for solution for infusion
Thiotepa
Read these instructions before preparing and administering TEPADINA.

1. PRESENTATION

TEPADINA is presented as 15 mg powder for concentrate for solution for infusion.
TEPADINA must be reconstituted and diluted before administration.

2. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING

As with other cytotoxic compounds, extreme care must be taken during the handling and preparation of TEPADINA solutions to avoid accidental contact with the skin or mucous membranes. Local reactions may occur following accidental exposure to thiotepa. Therefore, it is recommended to wear gloves before preparing the infusion solution. If the thiotepa solution comes into accidental contact with the skin, wash the affected area thoroughly and immediately with water and soap. In case of accidental contact of thiotepa with mucous membranes, copious washing with water is recommended.

Dosage calculation of TEPADINA
TEPADINA is administered at different dosages in combination with other chemotherapeutic agents prior to conventional haematopoietic progenitor cell transplantation (HPCT) in patients with haematological disorders or solid tumours.

The recommended dosage of TEPADINA in adult and paediatric patients depends on the type of HPCT (autologous or allogeneic) and the underlying disease.

Dosage in adults
AUTologous HPCT
Haematological disorders
The recommended dose in haematological disorders 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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

Central nervous system 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 HPCT, without exceeding a maximum total cumulative dose of 370 mg/m² (10 mg/kg) throughout the conditioning regimen.

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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

Solid tumours
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 into one or two daily infusions administered for 2 to 5 consecutive days prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning regimen.

Breast carcinoma
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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning regimen.

Brain 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 into one or two daily infusions administered for 3 to 4 consecutive days prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

Ovarian carcinoma
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 HPCT, without exceeding a maximum total cumulative dose of 500 mg/m² (13.51 mg/kg) throughout the conditioning regimen.

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 prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

ALLOGENEIC HPCT
Haematological disorders
The recommended dose in haematological disorders 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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 555 mg/m² (15 mg/kg) throughout the conditioning regimen.

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

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

Leukaemia
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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 555 mg/m² (15 mg/kg) throughout the conditioning regimen.

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

Dosage in paediatric patients
AUTologous HPCT
Solid tumours
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 for 2 to 3 consecutive days prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning regimen.

Brain 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 prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning regimen.

ALLOGENEIC HPCT
Haematological disorders
The recommended dose in haematological disorders 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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 375 mg/m² (15 mg/kg) throughout the conditioning regimen.

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

Thalassaemia
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 HPCT, without exceeding a maximum total cumulative dose of 250 mg/m² (10 mg/kg) throughout the conditioning regimen.

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 HPCT, without exceeding a maximum total cumulative dose of 375 mg/m² (15 mg/kg) throughout the conditioning regimen.

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 HPCT, without exceeding a maximum total cumulative dose of 250 mg/m² (10 mg/kg) throughout the conditioning regimen.

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

Reconstitution
TEPADINA must be reconstituted with 1.5 mL of water for injections.
Using a syringe with a pre-attached needle, withdraw 1.5 mL of water for injections using aseptic technique.
Inject the syringe contents through the rubber stopper into the vial.
Remove the syringe and needle and mix manually by repeated inversion.
Only use solutions that are colourless and free from particulate matter. Reconstituted solutions may occasionally appear opalescent; such solutions may still be administered.

Further dilution in the infusion bag
The reconstituted solution is hypotonic and must be further diluted prior to administration in 500 mL of sodium chloride 9 mg/mL (0.9%) for injection (1,000 mL if the dose exceeds 500 mg), or in an appropriate volume of sodium chloride 9 mg/mL (0.9%) for injection to achieve a final TEPADINA concentration between 0.5 and 1 mg/mL.

Administration
The infusion solution of TEPADINA must be visually inspected to exclude the presence of particulate matter prior to administration. Discard solutions containing precipitate.
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.
Administer TEPADINA aseptically as a 2- to 4-hour infusion at room temperature (approximately 25°C) under normal light conditions.
Before and after each infusion, thoroughly flush the indwelling catheter line with approximately 5 mL of sodium chloride 9 mg/mL (0.9%) for injection.

Disposal
TEPADINA is for single use only.
Any unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.

Package leaflet: Information for the user

TEPADINA 100 mg powder for concentrate for solution for infusion

thiotepa
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor.
If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

What TEPADINA is and what it is used for
What you need to know before using TEPADINA
How to use TEPADINA
Possible side effects
How to store TEPADINA
Contents of the pack and other information

1. What TEPADINA is and what it is used for

TEPADINA contains the active substance tiotepa, 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 allows transplantation of new bone marrow cells (hematopoietic progenitor cells), which in turn enable the body to produce healthy blood cells.
TEPADINA can be used in adults and in children and adolescents.

2. What you need to know before using TEPADINA

Do not use TEPADINA

if you are allergic to thiotepa,
if you are pregnant or suspect you may be pregnant,
if you are breastfeeding,
if you are receiving the yellow fever vaccine, live virus vaccines, or bacterial vaccines.

Warnings and precautions
Inform your doctor if you have:

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

Since TEPADINA destroys bone marrow cells responsible for blood cell production, regular blood tests will be performed during treatment to monitor your blood cell counts.
To prevent and treat infections, you will be given anti-infective agents.
TEPADINA may cause another type of tumour in the future. Your doctor will discuss this risk with you.

Other medicines and TEPADINA
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding and fertility
Before taking TEPADINA, inform your doctor if you are pregnant or suspect you may be pregnant. Do not use TEPADINA during pregnancy.
During treatment with TEPADINA, both men and women must use effective contraception. Men must not father a child during treatment with TEPADINA and for one year after stopping treatment.
It is not known whether this medicine is excreted in human milk. As a precautionary measure, women must not breastfeed during treatment with TEPADINA.
TEPADINA may impair male and female fertility. Male patients are advised to consider sperm preservation before starting therapy.

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. If you experience these symptoms, do not drive or operate machinery.

3. How to use TEPADINA

The doctor will calculate the dose based on body surface area or body weight, and according to the disease.
How TEPADINA is administered
TEPADINA is administered by a qualified healthcare professional as an intravenous infusion
(infusion into a vein) after dilution of the single vial. Each infusion will last 2–4 hours.
Frequency of administration
Infusions will be administered every 12 or 24 hours. Treatment may last up to 5 days. The frequency of administration and duration of treatment depend on the disease.

4. Possible side effects

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 include:

reduction in the number of circulating blood cells (an intended effect of the medicine to prepare you for the transplant infusion)
infection
liver problems, including blockage of a liver vein
the transplanted cells attack the body (graft-versus-host disease)
respiratory complications.
Your doctor will regularly monitor your blood cell counts and liver enzymes to detect and manage these events.

Side effects with TEPADINA may occur at various frequencies, defined as follows:
Very common side effects (may affect more than 1 in 10 people)

increased susceptibility to infections
systemic inflammatory condition affecting the whole body (sepsis)
reduced counts of white blood cells, platelets, and red blood cells (anaemia)
transplanted cells attacking the body (graft-versus-host disease)
dizziness, headache, blurred vision
uncontrolled body tremors (seizures)
tingling, prickling, and numbness sensations (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mouth mucosa (mucositis)
irritation of the stomach, oesophagus, and intestine
inflammation of the colon
anorexia, loss of appetite
high blood glucose levels
skin rash, itching, peeling
changes in skin colour (not to be confused with jaundice – see below)
redness of the skin (erythema)
hair loss
abdominal and back pain, general pain
muscle and joint pain
abnormal electrical activity of the heart (arrhythmia)
inflammation of lung tissue
enlarged liver
altered organ function
blockage of a liver vein (VOD – veno-occlusive disease)
yellowing of the skin and eyes (jaundice)
hearing loss
lymphatic obstruction
high blood pressure
increased liver, kidney, and digestive enzymes
abnormal blood electrolytes
weight gain
fever, weakness, chills
bleeding (haemorrhage)
nosebleeds
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
reduced sperm count
vaginal bleeding
absence of menstrual periods (amenorrhoea)
memory loss
delayed weight gain and height growth
bladder dysfunction
reduced testosterone production
insufficient production of thyroid hormones
reduced pituitary gland activity
confusion

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

anxiety, confusion
abnormal outward swelling of a brain artery (intracranial aneurysm)
elevated creatinine
allergic reactions
blockage of a blood vessel (embolism)
heart rhythm disorders
altered cardiac function
altered cardiovascular function
oxygen deficiency
fluid accumulation in the lungs (pulmonary oedema)
pulmonary bleeding
respiratory arrest
blood in the urine (haematuria) and moderate kidney failure
inflammation of the urinary bladder
difficulty urinating and reduced urine output (dysuria and oliguria)
increased levels of nitrogenous compounds in the blood (increased BUN)
cataract
altered liver function
cerebral haemorrhage
cough
constipation and stomach disturbances
intestinal obstruction
stomach perforation
altered muscle tone
lack of coordination in muscle movements
bruising due to low platelet count
menopausal symptoms
cancer (secondary primary tumour)
abnormal brain function
male and female infertility

Uncommon side 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 conditions (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 and may also be life-threatening.
damage to a part of the brain (so-called white matter) that may also be life-threatening (leukoencephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TEPADINA

Keep this medicine out of the sight and reach of children.
Do not use TEPADINA after the expiry date stated on the carton and vial label, after EXP. The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C-8 °C).
Do not freeze.
After reconstitution, the product is stable for 80 hours when stored at 2 °C-8 °C.
After dilution, the product is stable for up to 48 hours when stored at 2 °C-8 °C and up to 6 hours when stored at 25°C.
From a microbiological standpoint, the product should be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What TEPADINA contains

The active substance is tiotepa. One vial contains 100 mg of tiotepa. After reconstitution, each mL contains 10 mg of tiotepa (10 mg/mL).
TEPADINA does not contain any other ingredients.

Description of the appearance of TEPADINA and contents of the pack
TEPADINA is a white crystalline powder contained in a glass vial; each vial contains 100 mg of tiotepa.
Each carton contains one vial.

Marketing Authorization Holder and Manufacturer
ADIENNE S.r.l. S.U.
Via Galileo Galilei, 19
20867 Caponago (MB) Italy
Tel: +39-02 40700445
[email protected]

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Accord Healthcare bv Accord Healthcare AB
Tél: +32 51 79 40 12 Tel: +46 8 624 00 25

България Luxembourg/Luxemburg
Accord Healthcare Polska Sp. z o.o. Accord Healthcare bv
Teл.: +48 22 577 28 00 Tèl/Tel: +32 51 79 40 12

Česká republika Magyarország
Accord Healthcare Polska Sp. z o.o. Accord Healthcare Polska Sp. z o.o.
Tel: +48 22 577 28 00 Tel.: +48 22 577 28 00

Danmark Malta
Accord Healthcare AB Accord Healthcare Ireland Ltd
Tlf: + 46 8 624 00 25 Tel: +44 (0) 208 901 3370

Deutschland Nederland
Accord Healthcare GmbH Accord Healthcare B.V.
Tel: +49 89 700 9951 0 Tel: +31 30 850 6014

Eesti Norge
Accord Healthcare AB Accord Healthcare AB
Tel: +46 8 624 00 25 Tlf: + 46 8 624 00 25

Ελλάδα Österreich
Accord Healthcare Italia Srl Accord Healthcare GmbH
Τηλ: + 39 02 943 23 700 Tel: +43 (0)662 424899-0

España Polska
Accord Healthcare S.L.U. Accord Healthcare Polska Sp. z o.o.
Tel: +34 93 301 00 64 Tel.: +48 22 577 28 00

France Portugal
Accord Healthcare France SAS Accord Healthcare, Unipessoal Lda
Tél: +33 (0)320 401 770 Tel: +351 214 697 835

Hrvatska România
Accord Healthcare Polska Sp. z o.o. Accord Healthcare Polska Sp. z o.o.
Tel: +48 22 577 28 00 Tel: +48 22 577 28 00

Ireland Slovenija
Accord Healthcare Ireland Ltd Accord Healthcare Polska Sp. z o.o.
Tel: +44 (0)1271 385257 Tel: +48 22 577 28 00

Ísland Slovenská republika
Accord Healthcare AB Accord Healthcare Polska Sp. z o.o.
Sími: + 46 8 624 00 25 Tel: +48 22 577 28 00

Italia Suomi/Finland
Accord Healthcare Italia Srl Accord Healthcare Oy
Tel: +39 02 943 23 700 Puh/Tel: + 358 10 231 4180

Κύπρος Sverige
Accord Healthcare S.L.U. Accord Healthcare AB
Τηλ: + 34 93 301 00 64 Tel: + 46 8 624 00 25

Latvija United Kingdom (Northern Ireland)
Accord Healthcare AB Accord-UK Ltd
Tel: +46 8 624 00 25 Tel: +44 (0)1271 385257

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.

The following information is intended for healthcare professionals only.

INSTRUCTIONS FOR PREPARATION
TEPADINA 100 mg powder for concentrate for solution for infusion
Tiotepa
Read these instructions before preparing and administering TEPADINA.

1. PRESENTATION

TEPADINA is presented as 100 mg powder for concentrate for solution for infusion.
TEPADINA must be reconstituted and diluted prior to administration.

2. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING

General aspects
Appropriate procedures must be followed for the handling and disposal of antineoplastic medicinal products.
All transfer procedures require strict adherence to aseptic techniques, preferably using a vertical laminar flow safety cabinet.
As with other cytotoxic agents, extreme care must be taken when handling and preparing TEPADINA solutions to avoid accidental contact with the skin or mucous membranes.
Topical reactions may occur following accidental exposure to thiotepa. Therefore, it is recommended to wear gloves before preparing the infusion solution.
If the thiotepa solution comes into accidental contact with the skin, wash the affected area thoroughly and immediately with water and soap.
In case of accidental contact of thiotepa with mucous membranes, abundant washing with water is recommended.

Dosage calculation of TEPADINA
TEPADINA is administered at different doses in combination with other chemotherapeutic agents prior to conventional haematopoietic progenitor cell transplantation (HPCT) in patients with haematological disorders or solid tumours.
The recommended dosage of TEPADINA in adult and paediatric patients depends on the type of HPCT (autologous or allogeneic) and the underlying disease.

Dosage in adults
AUTLOGOUS HPCT
Haematological disorders
The recommended dose in haematological disorders 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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

PRIMARY CENTRAL NERVOUS SYSTEM 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 HPCT, without exceeding a maximum total cumulative dose of 370 mg/m² (10 mg/kg) throughout the conditioning regimen.

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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning regimen.

BRAIN 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 into one or two daily infusions administered for 3 to 4 consecutive days prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

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 HPCT, without exceeding a maximum total cumulative dose of 500 mg/m² (13.51 mg/kg) throughout the conditioning regimen.

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 prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

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

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

LEUKAEMIA
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 HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 555 mg/m² (15 mg/kg) throughout the conditioning regimen.

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

Dosage in paediatric patients
AUTLOGOUS HPCT
Solid tumours
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 for 2 to 3 consecutive days prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning regimen.

BRAIN 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 prior to autologous HPCT, depending on concomitant chemotherapeutic agents, without exceeding a maximum total cumulative dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning regimen.

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

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 HPCT, without exceeding a maximum total cumulative dose of 250 mg/m² (10 mg/kg) throughout the conditioning regimen.

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 HPCT, without exceeding a maximum total cumulative dose of 375 mg/m² (15 mg/kg) throughout the conditioning regimen.

GENETIC DISORDERS
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 HPCT, without exceeding a maximum total cumulative dose of 250 mg/m² (10 mg/kg) throughout the conditioning regimen.

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

Reconstitution
TEPADINA must be reconstituted with 10 mL of water for injections.
Using a syringe with a pre-attached needle, withdraw 10 mL of water for injections using aseptic technique.
Inject the contents of the syringe into the vial through the rubber stopper.
Remove the syringe and needle and mix manually by repeated inversions.
Use only clear, particle-free solutions. Reconstituted solutions may occasionally appear opalescent; such solutions may 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 of sodium chloride 9 mg/mL (0.9%) for injection (1,000 mL if the dose exceeds 500 mg), or in an appropriate volume of sodium chloride 9 mg/mL (0.9%) for injection to achieve a final TEPADINA concentration between 0.5 and 1 mg/mL.

Administration
The infusion solution for TEPADINA must be visually inspected to exclude the presence of particulate matter prior to administration. Discard solutions containing precipitate.
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.
Administer TEPADINA aseptically via a 2- to 4-hour infusion at room temperature (approximately 25°C) under normal light conditions.
Before and after each infusion, thoroughly flush the indwelling catheter line with approximately 5 mL of sodium chloride 9 mg/mL (0.9%) for injection.

Disposal
TEPADINA is for single use only.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.

Package leaflet: information for the user

TEPADINA 200 mg powder and solvent for solution for infusion

thiotepa
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor.
If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

What TEPADINA is and what it is used for
What you need to know before using TEPADINA
How to use TEPADINA
Possible side effects
How to store TEPADINA
Contents of the pack and other information

1. What TEPADINA is and what it is used for

TEPADINA contains the active substance tiotepa, 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 allows transplantation of new bone marrow cells (haematopoietic progenitor cells), which in turn enables the body to produce healthy blood cells.
TEPADINA can be used in adults, children, and adolescents.

2. What you need to know before using TEPADINA

Do not use TEPADINA

if you are allergic to thiotepa,
if you are pregnant or suspect you might be pregnant,
if you are breastfeeding,
if you are receiving the yellow fever vaccine, live virus vaccines, or bacterial vaccines.

Warnings and precautions
Inform your doctor if you have:

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

Other medicines and TEPADINA
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding and fertility
Before taking TEPADINA, inform your doctor if you are pregnant or suspect you might be pregnant. Do not use TEPADINA during pregnancy.
During treatment with TEPADINA, both men and women must use effective contraception. Men must not father a child during treatment with TEPADINA and for one year after stopping treatment.
It is not known whether this medicine is excreted in breast milk. As a precautionary measure, women must not breastfeed during treatment with TEPADINA.
TEPADINA may impair male and female fertility. Male patients are advised to consider sperm preservation before starting therapy.

Driving and using machines
Adverse reactions to thiotepa such as dizziness, headache, and blurred vision may affect your ability to drive or operate machinery. If you experience these symptoms, do not drive and do not operate machinery.

TEPADINA contains sodium
This medicine contains 709 mg (30.8 mmol) of sodium (the main component of table salt) per bag. This corresponds to 35.5% of the maximum daily recommended dietary intake for an adult.

3. How to use TEPADINA

The doctor will calculate the dosage according to body surface area or body weight, and depending on the disease.
How TEPADINA is administered
TEPADINA is administered by a qualified healthcare professional as an intravenous infusion
(IV infusion into a vein) after dilution of the single vial. Each infusion will last 2–4 hours.
Frequency of administration
Infusions will be given every 12 or 24 hours. Treatment may last up to 5 days. The frequency of administration and duration of treatment depend on the disease.

4. Possible side effects

Like all medicines, TEPADINA can cause side effects, although not everyone experiences them.
The most serious side effects of TEPADINA therapy or of the transplant procedure include:

reduction in the number of circulating blood cells (an intended effect of the medicine to prepare you for the transplant infusion)
infection
liver disorders, including blockage of a liver vein
the transplanted cells attacking the body (graft-versus-host disease)
respiratory complications.
Your doctor will regularly monitor your blood cell counts and liver enzymes to detect and manage these events.

Side effects with TEPADINA may occur at various frequencies, defined as follows.
Very common side effects (may affect more than 1 in 10 people)

increased susceptibility to infections
systemic inflammatory condition affecting the whole body (sepsis)
reduced counts of white blood cells, platelets, and red blood cells (anaemia)
transplanted cells attacking the body (graft-versus-host disease)
dizziness, headache, blurred vision
uncontrolled body tremors (seizures)
tingling, prickling, and numbness sensation (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mouth mucosa (mucositis)
irritation of the stomach, oesophagus, and intestine
inflammation of the colon
anorexia, loss of appetite
high blood glucose levels
skin rash, itching, desquamation
change in skin colour (do not confuse with jaundice – see below)
redness of the skin (erythema)
hair loss
abdominal and back pain, general pain
muscle and joint pain
abnormal electrical activity of the heart (arrhythmia)
inflammation of lung tissue
enlarged liver
altered organ function
blockage of a hepatic vein (VOD - veno-occlusive disease)
yellowing of the skin and eyes (jaundice)
hearing loss
lymphatic obstruction
high blood pressure
increased liver, renal, and digestive enzymes
abnormal blood electrolytes
weight gain
fever, weakness, chills
bleeding (haemorrhage)
nosebleeds
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
reduced sperm count
vaginal bleeding
absence of menstrual periods (amenorrhoea)
memory loss
delayed weight gain and growth in height
bladder dysfunction
decreased testosterone production
insufficient production of thyroid hormones
reduced pituitary gland activity
confusion

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

anxiety, confusion
abnormal outward bulging of a brain artery (intracranial aneurysm)
elevated creatinine
allergic reactions
blockage of a blood vessel (embolism)
heart rhythm disorders
altered cardiac function
altered cardiovascular function
oxygen deficiency
fluid accumulation in the lungs (pulmonary oedema)
lung bleeding
respiratory arrest
blood in the urine (haematuria) and moderate renal failure
inflammation of the urinary bladder
difficulty urinating and reduced urine output (dysuria and oliguria)
increased levels of nitrogen-containing compounds in the blood (increased BUN)
cataract
altered liver function
cerebral haemorrhage
cough
constipation and stomach disturbances
intestinal obstruction
stomach perforation
altered muscle tone
lack of coordination in muscular movements
bruising due to low platelet count
menopausal symptoms
cancer (secondary primary tumour)
abnormal brain function
male and female infertility

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

skin inflammation and peeling (erythrodermic psoriasis)
delirium, nervousness, hallucinations, agitation
gastrointestinal ulcer
inflammation of myocardial tissue (myocarditis)
abnormal heart conditions (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 and may also be life-threatening.
damage to a component of the brain (so-called white matter) that may also be life-threatening (leukoencephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or nurse.
You can also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TEPADINA

Keep this medicine out of the sight and reach of children.
Do not use TEPADINA after the expiry date stated on the packaging, on the label of the aluminium wrapper, and on the bag, after EXP. The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C-8 °C).
Do not freeze.
Keep the bag in the aluminium wrapper to protect the medicine from activation.
After activation and reconstitution of the bag, the product is stable for up to 48 hours if stored at 2 °C-8 °C and for up to 6 hours if stored at 25 °C.
From a microbiological standpoint, the medicine should be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What TEPADINA contains

The active substance is tiotepa. One bag contains 200 mg of tiotepa. After reconstitution with the solvent, each mL of solution contains 1 mg of tiotepa.
The other components are sodium chloride and water for injections (see section 2 “TEPADINA contains sodium”).

Description of the appearance of TEPADINA and contents of the pack
TEPADINA is supplied as a dual-chamber bag, one chamber containing 200 mg of powder and the other chamber containing 200 mL of sodium chloride 9 mg/mL (0.9%) solution for injection.
After reconstitution, the bag contains a clear, colourless solution for infusion.
Each bag is packaged in an aluminium overwrap.
Pack size: 1 bag.

Marketing Authorisation Holder and Manufacturer
ADIENNE S.r.l. S.U.
Via Galileo Galilei, 19
20867 Caponago (MB) Italy
Tel: +39-02 40700445
[email protected]

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder: