Thiotepa SeaCross 15 mg powder for concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Tiotepa Seacross 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Seacross 100 mg powder for concentrate for solution for infusion EFG

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are not listed in this leaflet. See section 4.

Leaflet contents

1. What Tiotepa Seacross is and what it is used for
2. What you need to know before using Tiotepa Seacross
3. How to use Tiotepa Seacross
4. Possible adverse reactions
5. How to store Tiotepa Seacross
6. Contents of the pack and other information

1. What Tiotepa Seacross is and what it is used for

Tiotepa Seacross contains the active substance tiotepa, a medicine belonging to the group of alkylating agents.

Tiotepa is used to prepare the patient for a bone marrow transplant. It works by destroying the cells in the bone marrow. This allows the patient to receive a transplant of new bone marrow cells (hematopoietic stem cells), which in turn enable the body to produce healthy blood cells.

Tiotepa can be used in adults, children, and adolescents.

2. What you need to know before using Tiotepa Seacross

Do not use Tiotepa

• if you are allergic to tiotepa,
• if you are pregnant or think you may be pregnant,
• if you are breastfeeding,
• if you are due to receive the yellow fever vaccine or other live virus or bacterial vaccines.

Warnings and precautions

Tell your doctor if you have:

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

Since Tiotepa destroys bone marrow cells responsible for producing blood cells, you will need to have regular blood tests during treatment to monitor your blood cell counts.

To prevent and treat infections, you will be given anti-infective agents.

Tiotepa may cause another type of cancer in the future. Your doctor will explain this risk to you.

Other medicines and Tiotepa

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding and fertility

Tell your doctor if you are pregnant or think you may be pregnant before receiving Tiotepa. You must not use Tiotepa during pregnancy.

Both women and men receiving Tiotepa should use effective contraceptive methods during treatment.

Men must not father a child during treatment with Tiotepa and for one year after the end of treatment.

It is unknown whether Tiotepa is excreted in human milk. As a precautionary measure, women should not breastfeed during treatment with Tiotepa.

Tiotepa may affect male and female fertility. Male patients should seek advice regarding sperm preservation before starting treatment.

Driving and using machines

Some adverse reactions of tiotepa, such as dizziness, headache and blurred vision, may affect your ability to drive and use machines. Do not drive or operate machinery if you are affected.

3. How to use Tiotepa Seacross

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

How Tiotepa is administered

Tiotepa must be administered by a qualified healthcare professional as an intravenous infusion (a drip into a vein) after dilution of each vial. Each infusion lasts 2–4 hours.

Frequency of administration

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

4. Possible adverse effects

Like all medicines, Tiotepa can cause adverse effects, although not everyone experiences them.

Some more serious side effects of treatment with Tiotepa or of the transplant procedure are:

• decrease in circulating blood cell counts (an expected effect of the medicine as part of your transplant preparation)
• infection
• liver problems, such as hepatic vein occlusion
• attack by the transplanted cells against your body (graft-versus-host disease)
• respiratory complications

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

Adverse effects of Tiotepa occur at certain frequencies, defined as follows:

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

• increased susceptibility to infections
• generalized inflammation (septicemia)
• decreased counts of white blood cells, platelets, and red blood cells (anemia)
• attack by transplanted cells against your body (graft-versus-host disease)
• dizziness, headache, blurred vision
• uncontrollable body tremors (seizures)
• tingling, prickling, or numbness sensation (paresthesia)
• partial loss of mobility
• cardiac arrest
• nausea, vomiting, diarrhea
• inflammation of the oral mucosa (mucositis)
• irritation of stomach, esophagus, and intestine
• inflammation of the colon
• anorexia, loss of appetite
• elevated blood glucose levels
• rash, pruritus, skin peeling
• skin color changes (should not be confused with jaundice – see below)
• redness of the skin (erythema)
• hair loss
• back and abdominal pain, general pain
• muscle and joint pain
• abnormal electrical activity in the heart (arrhythmia)
• inflammation of lung tissue
• liver enlargement
• impaired function of certain organs
• hepatic vein occlusion (veno-occlusive disease, VOD)
• yellowing of the skin and eyes (jaundice)
• hearing deterioration
• lymphatic obstruction
• high blood pressure
• liver enlargement, elevated renal and digestive enzymes
• abnormal blood electrolyte levels
• weight gain
• fever, general weakness, chills
• bleeding (hemorrhage)
• nosebleeds
• generalized swelling due to fluid retention (edema)
• pain or inflammation at the injection site
• eye infection (conjunctivitis)
• decreased sperm count
• vaginal bleeding
• absence of menstrual periods (amenorrhea)
• memory loss
• delayed weight and height gain
• bladder problems
• insufficient testosterone production
• insufficient thyroid hormone production
• reduced pituitary activity
• confusion

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

• anxiety, confusion
• abnormal dilation of an artery in the brain (intracranial aneurysm)
• elevated creatinine levels
• allergic reactions
• blockage of a blood vessel (embolism)
• irregular heart rhythm
• heart failure
• cardiovascular insufficiency
• oxygen deficiency
• fluid accumulation in the lungs (pulmonary edema)
• pulmonary hemorrhage
• respiratory arrest
• blood in the urine (hematuria) and moderate kidney failure
• inflammation of the urinary bladder
• discomfort during urination and reduced urine output (dysuria and oliguria)
• increased levels of nitrogen-containing components in the blood (elevated BUN)
• cataracts
• liver failure
• cerebral hemorrhage
• cough
• constipation and gastric discomfort
• intestinal obstruction
• stomach perforation
• changes in muscle tone
• general lack of coordination of muscular movements
• bruising associated with low platelet count
• menopausal symptoms
• cancer (secondary primary neoplasms)
• impaired brain function
• male and female infertility

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

• skin inflammation and peeling (erythrodermic psoriasis)
• delirium, nervousness, hallucinations, agitation
• gastrointestinal ulcer
• inflammation of cardiac muscle tissue (myocarditis)
• abnormal heart disease (cardiomyopathy)

Frequency not known (frequency cannot be estimated from available data)

• increased blood pressure in the arteries (blood vessels) of the lungs (pulmonary arterial hypertension)
• severe skin damage (e.g., severe lesions, bullae, etc.) that may affect the entire body surface and may even be fatal
• damage to a component of the brain (so-called white matter) that may be potentially fatal (leukoencephalopathy).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tiotepa Seacross

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

Do not use Tiotepa Seacross after the expiry date stated on the container after "EXP". The expiry date refers to the last day of the month indicated.

Store and transport refrigerated (2 °C–8 °C).

Do not freeze.

After reconstitution, the medicinal product remains stable for 72 hours when stored at 2 °C–8 °C.

After dilution, the medicinal product remains stable for 36 hours when stored at 2 °C–8 °C and for 6 hours when stored at 25 °C. From a microbiological standpoint, the product should be used immediately.

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.

6. Contents of the container and other information

Composition of Tiotepa Seacross

• The active substance is tiotepa.
• One vial of Tiotepa Seacross 15 mg contains 15 mg of tiotepa. After reconstitution, each ml contains 10 mg of tiotepa (10 mg/ml).

One vial of Tiotepa Seacross 100 mg contains 100 mg of tiotepa. After reconstitution, each ml contains 10 mg of tiotepa (10 mg/ml).

• Tiotepa Seacross does not contain any other component.

Appearance of the product and contents of the container

Tiotepa Seacross 15 mg is a white crystalline powder supplied in a glass vial containing 15 mg of tiotepa.

Tiotepa Seacross 100 mg is a white crystalline powder supplied in a glass vial containing 100 mg of tiotepa.

Each carton contains 1 vial.

Marketing Authorization Holder and Manufacturer

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

Local Representative

Pharmavic Ibérica, S.L.

C/ Compositor Lehmberg Ruiz

6 Edificio Ibiza, Oficina 7

29007 Málaga, (Spain)

Tel: 676295501

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany	Thiotepa Seacross 15mg powder for concentrate for infusion solution
Thiotepa Seacross 100mg powder for concentrate for infusion solution
Spain	Tiotepa Seacross 15mg powder for concentrate for perfusion solution EFG
Tiotepa Seacross 100mg powder for concentrate for perfusion solution EFG
France	THIOTEPA SEACROSS 15 mg, powder for solution for dilution for perfusion
THIOTEPA SEACROSS 100 mg, powder for solution for dilution for perfusion
Italy	TIOTEPA SEACROSS
Portugal	Tiotepa Seacross
United Kingdom (Northern Ireland)	Thiotepa Seacross 15 mg powder for concentrate for solution for infusion
Thiotepa Seacross 100 mg powder for concentrate for solution for infusion

Date of the most recent review of this summary: May 2024

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended for healthcare professionals only:

PREPARATION GUIDE

Tiotepa Seacross 15 mg powder for concentrate for solution for infusion EFG

Tiotepa Seacross 100 mg powder for concentrate for solution for infusion EFG

Tiotepa

Read this guide before preparing and administering Tiotepa Seacross.

1. PRESENTATION

Tiotepa Seacross is supplied as 15 mg powder for concentrate for solution for infusion.

Tiotepa Seacross is supplied as 100 mg powder for concentrate for solution for infusion.

Tiotepa Seacross must be reconstituted and diluted before administration.

2. SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

General

Appropriate procedures for handling and disposal of antineoplastic medicinal products must be followed. All transfer procedures must strictly comply with aseptic techniques, preferably using a vertical laminar flow safety cabinet. As with other cytotoxic compounds, extreme caution should be taken during handling and preparation of Tiotepa Seacross solutions to avoid accidental contact with skin or mucous membranes. Topical reactions may occur following accidental exposure to tiotepa. Therefore, the use of gloves is recommended during the preparation of the infusion solution. If the tiotepa solution comes into accidental contact with the skin, it should be immediately washed thoroughly with soap and water. If tiotepa comes into accidental contact with mucous membranes, they should be thoroughly rinsed with water.

Dose Calculation of Tiotepa Seacross

Tiotepa Seacross is administered at various doses and in combination with other chemotherapeutic agents to patients undergoing conventional hematopoietic stem cell transplantation (HSCT) due to hematological disorders or solid tumors.

The recommended dosage of Tiotepa Seacross in adult and pediatric patients depends on the type of HSCT (autologous or allogeneic) and the underlying disease.

Dosage in adults

AUTologous HSCT

Hematological disorders

The recommended dose in hematological disorders ranges between 125 mg/m²/day (3.38 mg/kg/day) and 300 mg/m²/day (8.10 mg/kg/day) as a single daily infusion administered for 2 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

LYMPHOMA

The recommended dose ranges between 125 mg/m²/day (3.38 mg/kg/day) and 300 mg/m²/day (8.10 mg/kg/day) as a single daily infusion administered for 2 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 900 mg/m² (24.32 mg/kg) throughout the conditioning regimen.

CENTRAL NERVOUS SYSTEM (CNS) LYMPHOMA

The recommended dose is 185 mg/m²/day (5 mg/kg/day) as a single daily infusion administered for 2 consecutive days prior to autologous HSCT, without exceeding a maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning regimen.

MULTIPLE MYELOMA

The recommended dose ranges between 150 mg/m²/day (4.05 mg/kg/day) and 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

Solid tumors

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

BREAST CANCER

The recommended dose ranges between 120 mg/m²/day (3.24 mg/kg/day) and 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 to 5 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 800 mg/m² (21.62 mg/kg) throughout the conditioning regimen.

CNS TUMORS

The recommended dose ranges between 125 mg/m²/day (3.38 mg/kg/day) and 250 mg/m²/day (6.76 mg/kg/day), divided into one or two daily infusions administered for 3 to 4 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total 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 HSCT, without exceeding a maximum cumulative total dose of 500 mg/m² (13.51 mg/kg) throughout the conditioning regimen.

GERM CELL TUMORS

The recommended dose ranges between 150 mg/m²/day (4.05 mg/kg/day) and 250 mg/m²/day (6.76 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 750 mg/m² (20.27 mg/kg) throughout the conditioning regimen.

ALLOGENEIC HSCT

Hematological disorders

The recommended dose in hematological disorders ranges between 185 mg/m²/day (5 mg/kg/day) and 481 mg/m²/day (13 mg/kg/day), divided into one or two daily infusions administered for 1 to 3 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 555 mg/m² (15 mg/kg) throughout the conditioning regimen.

LYMPHOMA

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

MULTIPLE MYELOMA

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

LEUKEMIA

The recommended dose ranges between 185 mg/m²/day (5 mg/kg/day) and 481 mg/m²/day (13 mg/kg/day), divided into one or two daily infusions administered for 1 or 2 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total 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 prior to allogeneic HSCT, without exceeding a maximum cumulative total dose of 370 mg/m² (10 mg/kg) throughout the conditioning regimen.

Dosage in pediatric patients

AUTologous HSCT

Solid tumors

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

CNS TUMORS

The recommended dose ranges between 250 mg/m²/day (10 mg/kg/day) and 350 mg/m²/day (14 mg/kg/day) as a single daily infusion administered for 3 consecutive days prior to autologous HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 1,050 mg/m² (42 mg/kg) throughout the conditioning regimen.

ALLOGENEIC HSCT

Hematological disorders

The recommended dose in hematological disorders ranges between 125 mg/m²/day (5 mg/kg/day) and 250 mg/m²/day (10 mg/kg/day), divided into one or two daily infusions administered for 1 to 3 consecutive days prior to allogeneic HSCT, depending on combination with other chemotherapeutic drugs, without exceeding a maximum cumulative total dose of 375 mg/m² (15 mg/kg) throughout the conditioning regimen.

LEUKEMIA

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

THALASSEMIA

The recommended dose ranges between 200 mg/m²/day (8 mg/kg/day) and 250 mg/m²/day (10 mg/kg/day), divided into two daily infusions prior to allogeneic HSCT, without exceeding a maximum cumulative total 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 HSCT, without exceeding a maximum cumulative total 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 HSCT, without exceeding a maximum cumulative total dose of 250 mg/m² (10 mg/kg) throughout the conditioning regimen.

SICKLE CELL ANEMIA

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

Reconstitution

Tiotepa Seacross 15 mg powder for concentrate for solution for infusion must be reconstituted with 1.5 ml of sterile water for injectable preparations. Using a syringe equipped with a needle, withdraw 1.5 ml of sterile water for injection under aseptic conditions.

Tiotepa Seacross 100 mg powder for concentrate for solution for infusion must be reconstituted with 10 ml of sterile water for injectable preparations. Using a syringe equipped with a needle, withdraw 10 ml of sterile water for injection under aseptic conditions.

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

Remove the syringe and needle and mix manually by repeated inversion of the vial.

Only clear, colorless solutions free from particles should be used. Reconstituted solutions may occasionally show opalescence; such solutions may still be administered.

Further dilution in the infusion bag

The reconstituted solution is hypotonic and must be diluted before administration with 500 ml of 9 mg/ml sodium chloride (0.9%) solution for injection (1,000 ml if the dose exceeds 500 mg), or with an appropriate volume of 9 mg/ml sodium chloride (0.9%) solution to achieve a final concentration of Tiotepa Seacross between 0.5 and 1 mg/ml.

Administration

Tiotepa Seacross solution for infusion should be visually inspected for the presence of particles before administration. Solutions containing precipitates should be discarded.

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

Tiotepa Seacross must be administered under aseptic conditions by infusion over 2–4 hours at room temperature (approximately 25 °C) and under normal lighting conditions.

Before and after each infusion, the indwelling catheter should be flushed with approximately 5 ml of 9 mg/ml sodium chloride (0.9%) solution for injection.

Disposal

Tiotepa Seacross is for single use only.

Any unused medicinal product and all materials that have been in contact with it must be disposed of in accordance with local regulations.