TIOTEPA SEACROSS 15 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Tiotepa Seacross 15 mg powder for concentrate for solution for infusionEFG

Tiotepa Seacross 100 mg powder for concentrate for solution for infusionEFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if you think they might be unrelated to the medicine. See section 4.

Contents of the pack

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

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

Tiotepa Seacross contains tiotepa as the active substance, a medicine that belongs 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 you use 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 going to receive the yellow fever vaccine with live virus and bacterial vaccines.

Warnings and precautions

Tell your doctor if you have:

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

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

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

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

Other medicines and Tiotepa

Tell your doctor if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

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

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

Men should not father a child during treatment with Tiotepa or for a year after the end of treatment.

It is not known if Tiotepa is excreted in breast milk. As a precaution, women should not breastfeed during treatment with Tiotepa.

Tiotepa may affect male and female fertility. Male patients should seek advice on 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 use machines if you are affected.

3. How to use Tiotepa Seacross

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

How Tiotepa is administered

Tiotepa must be administered by a qualified healthcare professional via intravenous infusion (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 the duration of treatment will depend on your disease.

4. Possible side effects

Like all medicines, Tiotepa can cause side effects, although not everybody gets them.

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

• decrease in blood cell counts (expected effect of the medicine as preparation for transplant)
• infection
• liver problems, such as blockage of a liver vein
• graft-versus-host disease (GVHD)
• respiratory complications

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

The side effects of Tiotepa occur with certain frequencies, which are defined below:

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

• increased risk of infections
• generalized inflammation (septicemia)
• decrease in white blood cell, platelet, and red blood cell counts (anemia)
• graft-versus-host disease (GVHD)
• dizziness, headache, blurred vision
• uncontrolled body tremors (seizures)
• tingling, numbness, or prickling sensations (paresthesia)
• partial loss of mobility
• cardiac arrest
• nausea, vomiting, diarrhea
• inflammation of the mouth mucosa (mucositis)
• irritation of the stomach, esophagus, intestine
• inflammation of the colon
• loss of appetite, anorexia
• elevated blood glucose
• rash, itching, peeling
• skin color changes (not to be confused with jaundice - see below)
• redness of the skin (erythema)
• hair loss
• back and abdominal pain
• muscle and joint pain
• abnormal heart rhythm (arrhythmia)
• inflammation of lung tissue
• enlargement of the liver
• altered function of some organs
• blockage of a liver vein (veno-occlusive disease, VOD)
• yellowing of the skin and eyes (jaundice)
• hearing impairment
• lymphatic obstruction
• high blood pressure
• enlargement of the liver, elevated kidney and digestive enzymes
• abnormal blood electrolyte values
• 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
• bladder problems
• insufficient testosterone production
• insufficient thyroid hormone production
• reduced pituitary activity
• state of confusion

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

• anxiety, confusion
• abnormal dilation of a brain artery (intracranial aneurysm)
• elevated creatinine
• allergic reactions
• blockage of a blood vessel (embolism)
• abnormal heart rhythm
• heart failure
• cardiovascular disability
• oxygen deficiency
• fluid accumulation in the lungs (pulmonary edema)
• pulmonary bleeding
• respiratory arrest
• blood in the urine (hematuria) and moderate kidney failure
• inflammation of the urinary bladder
• discomfort while urinating and decreased urine production (dysuria and oliguria)
• elevated blood urea nitrogen (BUN)
• cataracts
• liver failure
• cerebral bleeding
• cough
• constipation and stomach discomfort
• intestinal obstruction
• stomach perforation
• changes in muscle tone
• general lack of coordination of muscle movements
• bruises associated with low platelet count
• menopausal symptoms
• cancer (secondary primary malignancies)
• altered brain function
• male and female infertility

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

• inflammation and peeling of the skin (erythrodermic psoriasis)
• delirium, nervousness, hallucinations, agitation
• gastrointestinal ulcers
• inflammation of the heart muscle (myocarditis)
• abnormal heart disease (myocardial disease)

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 can affect the entire body surface, which can be life-threatening
• damage to a component of the brain (so-called white matter) that can be life-threatening (leukoencephalopathy)

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if you think they might be unrelated to the medicine. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side 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 which is stated on the carton after "EXP". The expiry date refers to the last day of the month shown.

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

Do not freeze.

After reconstitution, the product is stable for 72 hours when stored at 2°C-8°C.

After dilution, the product is stable for 36 hours when stored at 2°C-8°C and for 6 hours when stored at 25°C. From a microbiological point of view, the product should be used immediately.

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

6. Container Content and Additional Information

Composition of Tiotepa Seacross

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

A 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 components.

Appearance of the Product and Container Content

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 box 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)

Phone: 676295501

This Medicinal Product is Authorized in the Member States of the European Economic Area under the Following Names:

Date of the Last Revision of this Leaflet:May 2024

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

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This Information is Intended Only for Healthcare Professionals:

PREPARATION GUIDE

Tiotepa Seacross15 mg powder for concentrate for solution for perfusion EFG

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

Tiotepa

Read this guide before preparing and administering Tiotepa Seacross.

1. Presentation

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

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

Tiotepa Seacross must be reconstituted and diluted before administration.

1. Special Precautions for Disposal and Other Handling

Generalities

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

Calculation of the Dose of Tiotepa Seacross

Tiotepa Seacross is administered in different doses and in combination with other chemotherapeutic medicinal products to patients who are to receive a conventional hematopoietic stem cell transplant (HSCT) for hematological diseases or solid tumors.

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

Posology in Adults

AUTologous HSCT

Hematological Diseases

The recommended dose in hematological diseases ranges from 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion, administered for 2 to 4 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 900 mg/m2 (24.32 mg/kg) during the entire conditioning treatment.

LYMPHOMA

The recommended dose ranges from 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion, administered for 2 to 4 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 900 mg/m2 (24.32 mg/kg) during the entire conditioning treatment.

LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM (CNS)

The recommended dose is 185 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before an autologous HSCT, without exceeding the maximum accumulated dose of 370 mg/m2 (10 mg/kg) during the entire conditioning treatment.

MULTIPLE MYELOMA

The recommended dose ranges from 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 750 mg/m2 (20.27 mg/kg) during the entire conditioning treatment.

Solid Tumors

The recommended dose in solid tumors ranges from 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) divided into one or two daily infusions, administered for 2 to 5 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 800 mg/m2 (21.62 mg/kg) during the entire conditioning treatment.

BREAST CANCER

The recommended dose ranges from 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered for 3 to 5 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 800 mg/m2 (21.62 mg/kg) during the entire conditioning treatment.

TUMORS OF THE CNS

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 before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 750 mg/m2 (20.27 mg/kg) during the entire conditioning treatment.

OVARIAN CANCER

The recommended dose is 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before an autologous HSCT, without exceeding the maximum accumulated dose of 500 mg/m2 (13.51 mg/kg) during the entire conditioning treatment.

STEM CELL TUMORS

The recommended dose ranges from 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 750 mg/m2 (20.27 mg/kg) during the entire conditioning treatment.

ALLOGENEIC HSCT

Hematological Diseases

The recommended dose in hematological diseases ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided into one or two daily infusions, administered for 1 to 3 consecutive days before an allogeneic HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 555 mg/m2 (15 mg/kg) during the entire conditioning treatment.

LYMPHOMA

The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided into two daily infusions before an allogeneic HSCT, without exceeding the maximum accumulated dose of 370 mg/m2 (10 mg/kg) during the entire conditioning treatment.

MULTIPLE MYELOMA

The recommended dose is 185 mg/m2/day (5 mg/kg/day) as a single daily infusion before an allogeneic HSCT, without exceeding the maximum accumulated dose of 185 mg/m2 (5 mg/kg) during the entire conditioning treatment.

LEUKEMIA

The recommended dose ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided into one or two daily infusions, administered for 1 or 2 consecutive days before an allogeneic HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 555 mg/m2 (15 mg/kg) during the entire conditioning treatment.

THALASSEMIA

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

Posology in Pediatric Patients

AUTologous HSCT

Solid Tumors

The recommended dose in solid tumors ranges from 150 mg/m2/day (6 mg/kg/day) to 350 mg/m2/day (14 mg/kg/day) as a single daily infusion, administered for 2 to 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 1,050 mg/m2 (42 mg/kg) during the entire conditioning treatment.

TUMORS OF THE CNS

The recommended dose ranges from 250 mg/m2/day (10 mg/kg/day) to 350 mg/m2/day (14 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before an autologous HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 1,050 mg/m2 (42 mg/kg) during the entire conditioning treatment.

ALLOGENEIC HSCT

Hematological Diseases

The recommended dose in hematological diseases ranges from 125 mg/m2/day (5 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided into one or two daily infusions, administered for 1 to 3 consecutive days before an allogeneic HSCT, depending on the combination with other chemotherapeutic medicinal products, without exceeding the maximum accumulated dose of 375 mg/m2 (15 mg/kg) during the entire conditioning treatment.

LEUKEMIA

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

THALASSEMIA

The recommended dose ranges from 200 mg/m2/day (8 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided into two daily infusions, administered before an allogeneic HSCT, without exceeding the maximum accumulated dose of 250 mg/m2 (10 mg/kg) during the entire conditioning treatment.

REFRACTORY CYTOPENIA

The recommended dose is 125 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before an allogeneic HSCT, without exceeding the maximum accumulated dose of 375 mg/m2 (15 mg/kg) during the entire conditioning treatment.

GENETIC DISEASES

The recommended dose is 125 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before an allogeneic HSCT, without exceeding the maximum accumulated dose of 250 mg/m2 (10 mg/kg) during the entire conditioning treatment.

SICKLE CELL ANEMIA

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

Reconstitution

Tiotepa Seacross 15 mg powder for concentrate for solution for perfusion must be reconstituted with 1.5 ml of sterile water for injectable preparations. With a syringe equipped with a needle, extract 1.5 ml of sterile water for injectables under aseptic conditions.

Tiotepa Seacross 100 mg powder for concentrate for solution for perfusion must be reconstituted with 10 ml of sterile water for injectable preparations. With a syringe equipped with a needle, extract 10 ml of sterile water for injectables under 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 repeatedly inverting the vial.

Only clear, particle-free solutions will 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 injectable solution containing 9 mg/ml of sodium chloride (0.9%) for injectables (1,000 ml if the dose is higher than 500 mg) or with an appropriate volume of sodium chloride 9 mg/ml (0.9%) to obtain a final concentration of Tiotepa Seacross between 0.5 and 1 mg/ml.

Administration

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

The infusion solution should be administered to patients using an infusion set equipped with a 0.2 μm in-line 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 permanent catheter should be flushed with approximately 5 ml of injectable solution containing 9 mg/ml of sodium chloride (0.9%).

Elimination

Tiotepa Seacross is for single use.

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