Prospect: 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

thiotepa

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any doubts, consult your doctor.

-If you experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

1.What is Thiotepa Riemser and for what it is used

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 package and additional information

Thiotepa Riemser contains thiotepa as the active ingredient, a medication that belongs to the group of alkylating agents.

Thiotepa Riemser is used to prepare the patient for a bone marrow transplant. It acts by destroying bone marrow cells. In this way, it can receive a transplant of new bone marrow cells (hematopoietic stem cells), which in turn allow the body to produce healthy blood cells.

Thiotepa Riemser may be used in adults, children, and adolescents.

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 to receive the yellow fever vaccine, live virus and bacterial vaccines.

Warnings and precautions

Inform your doctor if you have:

-liver or kidney problems,

-heart or lung problems,

-seizures/epileptic crises or have had them in the past (if treated with phenytoin or fosphenytoin).

Since Thiotepa Riemser destroys the bone marrow cells responsible for producing blood cells, you will need to have periodic blood tests during treatment to verify your blood cell counts.

Antibiotics will be provided for the prevention and treatment of infections.

Thiotepa Riemser may cause another type of cancer in the future. Your doctor will explain this type of risk.

Other medications and Thiotepa Riemser

Inform your doctor if you are taking, have taken recently or may need to take any other medication.

Pregnancy, breastfeeding and fertility

Inform your doctor if you are pregnant or think you may be pregnant before starting to receive Thiotepa Riemser. Do not use Thiotepa Riemser during pregnancy.

Both men and women using Thiotepa Riemser must use effective contraceptive methods during treatment. Men should not father any children while receiving treatment and during the year following its completion.

The excretion of this medication in breast milk is unknown. As a precaution, women should not breastfeed during treatment with Thiotepa Riemser.

Thiotepa Riemser may affect male and female fertility. Male patients should seek advice for sperm conservation before starting treatment.

Driving and operating machinery

Some side effects of thiotepa, such as dizziness, headache and blurred vision, may affect your ability to drive and operate machinery. If you notice these side effects, do not drive or operate machinery.

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

How Thiotepa Riemser is administered

Thiotepa Riemser must be administered by a qualified healthcare professional through intravenous infusion (drip in a vein) after diluting each vial. Each infusion lasts 2-4 hours.

Administration frequency

You will receive infusions every 12 or 24 hours. Treatment may last up to 5 days. The administration frequency and treatment duration will depend on your disease.

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

Some of the most serious side effects of treatment with Thiotepa Riemser or the transplant procedure are:

-Decrease in circulating blood cell counts (expected effect of the medicine as preparation for your transplant)

-Infection

-Liver problems, such as hepatic vein occlusion

-Transplant rejection (graft-versus-host disease)

-Respiratory complications

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

Other side effects of Thiotepa Riemser, which may occur with certain frequencies, are listed below:

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

-Increased susceptibility to infections

-Generalized inflammation (septicemia)

-Decrease in white blood cell, platelet, and red blood cell counts (anemia)

-Transplant rejection (graft-versus-host disease)

-Dizziness, headache, blurred vision

-Uncontrolled body tremors (convulsions)

-Prickling, tingling, or numbness (paresthesia)

-Partial loss of mobility

-Cardiac arrest

-Nausea, vomiting, diarrhea

-Mucositis (inflammation of the oral mucosa)

-Gastrointestinal irritation

-Colon inflammation

-Loss of appetite, weight loss

-Elevated blood glucose

-Rash, itching, peeling

-Alteration of skin color (not to be confused with jaundice - see below)

-Redness of the skin (erythema)

-Hair loss

-Back and abdominal pain, pain

-Muscle and joint pain

-Abnormal heart rhythm (arrhythmia)

-Pulmonary tissue inflammation

-Enlargement of the liver

-Alteration of organ function

-Hepatic vein occlusion (veno-occlusive disease, VOD)

-Jaundice (yellowing of the skin and eyes)

-Impaired hearing

-Lymphatic occlusion

-High blood pressure

-Elevated liver, renal, and digestive enzymes

-Abnormal electrolyte levels in the blood

-Weight gain

-Fever, general weakness, chills

-Bleeding (hemorrhage)

-Nasal bleeding

-General swelling due to fluid retention (edema)

-Pain or inflammation at the injection site

-Eye infection (conjunctivitis)

-Decreased sperm count

-Vaginal bleeding

-Absence of menstrual periods (amenorrhea)

-Memory loss

-Delayed weight and height gain

-Urinary problems

-Inadequate testosterone production

-Inadequate thyroid hormone production

-Decreased pituitary activity

-Confusion state

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

-Anxiety, confusion

-Abnormal dilation of one of the arteries in the brain (intracranial aneurysm)

-Elevated creatinine

-Allergic reactions

-Arterial occlusion (embolism)

-Alteration of heart rhythm

-Heart failure

-Cardiovascular incapacity

-Oxygen deficiency

-Pulmonary edema (fluid accumulation in the lungs)

-Pulmonary hemorrhage

-Respiratory arrest

-Blood in the urine (hematuria) and moderate renal insufficiency

-Urinary tract inflammation

-Difficulty urinating and decreased urine production (dysuria and oliguria)

-Increased nitrogen components in the blood

-Cataracts

-Liver insufficiency

-Cerebral hemorrhage

-Tos

-Constipation and gastrointestinal discomfort

-Intestinal obstruction

-Stomach perforation

-Muscle tone changes

-General lack of coordination of muscle movements

-Hematomas associated with low platelet counts

-Menopausal symptoms

-Cancer (main secondary neoplasms)

-Cerebral function alteration

-Male and female infertility

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

-Psoriasis erythrodérmica (inflammation and peeling of the skin)

-Delirium, nervousness, hallucinations, agitation

-Gastrointestinal ulcer

-Myocarditis (inflammation of the heart muscle)

-Abnormal heart disease (myocardialopathy)

Unknown frequency (frequency cannot be estimated from available data)

-Pulmonary arterial hypertension (high blood pressure in the pulmonary arteries)

-Severe skin damage (e.g., severe lesions, bullae, etc.) that can affect the entire body surface, which can be even fatal

-Damage to a component of the brain (the so-called white matter) that can be even potentially fatal (leucoencephalopathy)

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial after "CAD/EXP". The expiration date is the last day of the month indicated.

Store and transport refrigerated (between 2 °C and 8 ºC).

Do not freeze.

After reconstitution, the medication remains stable for 8 hours when stored at between 2 °C and 8 ºC.

After dilution, the medication remains stable for 24 hours when stored at 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.

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

Composition of Thiotepa Riemser

Thiotepa Riemser 15 mg powder for concentrate for solution for infusionEFG

-The active substance is thiotepa. A 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 infusionEFG

-The active substance is thiotepa. A 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 component.

Aspect of the product and content of the package

Thiotepa Riemser 15 mg powder for concentrate for solution for infusionEFG

Thiotepa Riemser is a white crystalline powder that is supplied in a glass vial containing 15 mg of thiotepa.

Thiotepa Riemser 100 mg powder for concentrate for solution for infusionEFG

Thiotepa Riemser is a white crystalline powder that is supplied in a glass vial containing 100 mg of thiotepa.

Each box contains 1 vial.

Marketing Authorization Holder

Esteve Pharmaceuticals GmbH

Hohenzollerndamm 150-151

14199 Berlin

Germany

Responsible for manufacturing

HWI development GmbH

Straßburger Str. 77

77767 Appenweier

Germany

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet: {MM/AAAA}.

Other sources of information

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

This information is intended solely for healthcare professionals:

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 preparation and administration of Thiotepa Riemser.

1.PRESENTATION

Thiotepa Riemser 15 mg powder for concentrate for solution for infusionEFG

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 infusionEFG

Thiotepa Riemser is supplied as 100 mg of powder for concentrate for solution for infusion.

Thiotepa Riemser must be reconstituted and diluted before administration.

2.SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

General

Proper procedures for handling and disposal of anticancer drugs will be taken into account. All transfer procedures will have to comply strictly with aseptic techniques, preferably using a vertical laminar flow safety cabinet. As with other cytotoxic compounds, extreme caution will be exercised during the handling and preparation of Thiotepa Riemser solutions to avoid accidental contact with the skin or mucous membranes. Accidental exposure to thiotepa may cause topical reactions. Therefore, the use of gloves during the preparation of the infusion solution is recommended. If thiotepa accidentally comes into contact with the skin, it should be washed immediately with water and soap. If thiotepa accidentally comes into contact with mucous membranes, they should be washed immediately with water.

Calculation of the dose of Thiotepa Riemser

Thiotepa Riemser is administered in various doses and in combination with other chemotherapy drugs to patients who are to receive a conventional hematopoietic stem cell transplant (HSCT) for hematological diseases or solid tumors.

The recommended dose of Thiotepa Riemser in adult and pediatric patients depends on the type of HSCT (autologous or allogenic) and the disease.

Adult dose

Hematological diseases

The recommended dose in hematological diseases varies between 125 mg/m2/day (3.38 mg/kg/day) and 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion, administered over 2 to 4 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 900 mg/m2(24.32 mg/kg), throughout the conditioning treatment.

Lymphoma

The recommended dose varies between 125 mg/m2/day (3.38 mg/kg/day) and 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion, administered over 2 to 4 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative 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 over 2 consecutive days before an autologous HSCT, without exceeding the maximum cumulative dose of 370 mg/m2(10 mg/kg), throughout the conditioning treatment.

Multiple Myeloma

The recommended dose varies between 150 mg/m2/day (4.05 mg/kg/day) and 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered over 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 750 mg/m2(20.27 mg/kg), throughout the conditioning treatment.

Solid tumors

The recommended dose in solid tumors varies between 120 mg/m2/day (3.24 mg/kg/day) and 250 mg/m2/day (6.76 mg/kg/day) divided into one or two daily infusions, administered over 2 to 5 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 800 mg/m2(21.62 mg/kg), throughout the conditioning treatment.

Breast cancer

The recommended dose varies between 120 mg/m2/day (3.24 mg/kg/day) and 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered over 3 to 5 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 800 mg/m2(21.62 mg/kg), throughout the conditioning treatment.

CNS tumors

The recommended dose varies between 125 mg/m2/day (3.38 mg/kg/day) and 250 mg/m2/day (6.76 mg/kg/day) divided into one or two daily infusions, administered over 3 to 4 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative 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 over 2 consecutive days before an autologous HSCT, without exceeding the maximum cumulative dose of 500 mg/m2(13.51 mg/kg), throughout the conditioning treatment.

Germinative cell tumors

The recommended dose varies between 150 mg/m2/day (4.05 mg/kg/day) and 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered over 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 750 mg/m2(20.27 mg/kg), throughout the conditioning treatment.

Allogenic HSCT

Hematological diseases

The recommended dose in hematological diseases varies between 185 mg/m2/day (5 mg/kg/day) and 481 mg/m2/day (13 mg/kg/day) divided into one or two daily infusions, administered over 1 to 3 consecutive days before an allogenic HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative 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 before an allogenic HSCT, without exceeding the maximum cumulative 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 before an allogenic HSCT, without exceeding the maximum cumulative dose of 185 mg/m2(5 mg/kg), throughout the conditioning treatment.

Leukemia

The recommended dose varies between 185 mg/m2/day (5 mg/kg/day) and 481 mg/m2/day (13 mg/kg/day) divided into one or two daily infusions, administered over 1 to 2 consecutive days before an allogenic HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 555 mg/m2(15 mg/kg), throughout the conditioning treatment.

Talassemia

The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided into two daily infusions, administered before an allogenic HSCT, without exceeding the maximum cumulative dose of 370 mg/m2(10 mg/kg), throughout the conditioning treatment.

Pediatric dose

Autologous HSCT

Solid tumors

The recommended dose in solid tumors varies between 150 mg/m2/day (6 mg/kg/day) and 350 mg/m2/day (14 mg/kg/day) as a single daily infusion, administered over 2 to 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 1 050 mg/m2(42 mg/kg), throughout the conditioning treatment.

CNS tumors

The recommended dose varies between 250 mg/m2/day (10 mg/kg/day) and 350 mg/m2/day (14 mg/kg/day) as a single daily infusion, administered over 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative dose of 1 050 mg/m2(42 mg/kg), throughout the conditioning treatment.

Allogenic HSCT

Hematological diseases

The recommended dose in hematological diseases varies between 125 mg/m2/day (5 mg/kg/day) and 250 mg/m2/day (10 mg/kg/day) divided into one or two daily infusions, administered over 1 to 3 consecutive days before an allogenic HSCT, depending on the combination with other chemotherapy drugs, without exceeding the maximum cumulative 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 before an allogenic HSCT, without exceeding the maximum cumulative dose of 250 mg/m2(10 mg/kg), throughout the conditioning treatment.

Talassemia

The recommended dose varies between 200 mg/m2/day (8 mg/kg/day) and 250 mg/m2/day (10 mg/kg/day) divided into two daily infusions, administered before an allogenic HSCT, without exceeding the maximum cumulative dose of 250 mg/m2(10 mg/kg), throughout the conditioning treatment.

Citopenia refractoria

The recommended dose is 125 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered over 3 consecutive days before an allogenic HSCT, without exceeding the maximum cumulative 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 over 2 consecutive days before an allogenic HSCT, without exceeding the maximum cumulative dose of 250 mg/m2(10 mg/kg), throughout the conditioning treatment.

Falciform anemia

The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided into two daily infusions, administered before an allogenic HSCT, without exceeding the maximum cumulative dose of 250 mg/m2(10 mg/kg), throughout the conditioning treatment.

Reconstitution

Thiotepa Riemser 15 mg powder for concentrate for solution for infusionEFG

Thiotepa Riemser must be reconstituted with 1.5 ml of sterile water for injection.

Using a syringe provided with a needle, withdraw 1.5 ml of sterile water for injection in aseptic conditions.

Thiotepa Riemser 100 mg powder for concentrate for solution for infusionEFG

Thiotepa Riemser must be reconstituted with 10 ml of sterile water for injection.

Using a syringe provided with a needle, withdraw 10 ml of sterile water for injection in aseptic conditions.

Inject the contents of the syringe into the vial by piercing the rubber stopper.

Remove the syringe and needle and mix manually by inverting the vial repeatedly. Only colourless, transparent solutions without particles will be used. Reconstituted solutions may occasionally show opalescence; such solutions may still be administered.

Additional dilution in the infusion bag

The reconstituted solution is hypotonic and must be further diluted before administration with 500 ml of sodium chloride 9 mg/ml (0.9%) injection solution (1000 ml if the dose is greater than 500 mg) or with an appropriate volume of sodium chloride 9 mg/ml (0.9%) injection solution to obtain a final Thiotepa Riemser concentration of between 0.5 and 1 mg/ml.

Administration

Thiotepa Riemser infusion solution must be visually inspected for the presence of particles before administration. Solutions containing precipitates must be discarded.

The infusion solution must be administered to patients using an infusion device equipped with a 0.2 µm in-line filter. Filtration does not alter the potency of the solution.

Thiotepa Riemser must be administered in aseptic conditions using an infusion device over 2 to 4 hours at room temperature (approximately 25 °C) and under normal lighting conditions.

Before and after each infusion, the permanent catheter must be washed with approximately 5 ml of sodium chloride 9 mg/ml (0.9%) injection solution.

Disposal

Thiotepa Riemser is for single use only.

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.