TEPADINA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/VIAL

4.1 Therapeutic indications

TEPADINA is indicated, in combination with other chemotherapy medicinal products:

• with or without total body irradiation (TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients;
• when high dose chemotherapy with HPCT support is appropriate for the treatment of breast cancer in adult patients and CNS tumours in paediatric patients.

4.3 Contraindications

Hypersensitivity to the active substance.

Pregnancy and lactation (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Posology and method of administration

TEPADINA administration must be supervised by a physician experienced in conditioning treatment prior to haematopoietic progenitor cell transplantation.

Posology

TEPADINA is administered at different doses, in combination with other chemotherapeutic medicinal products, in patients with haematological diseases or solid tumours prior to HPCT.

TEPADINA posology is reported, in adult and paediatric patients, according to the type of HPCT (autologous or allogeneic) and disease.

Adults

AUTOLOGOUS HPCT

Haematological diseases

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

LYMPHOMA

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

CENTRAL NERVOUS SYSTEM (CNS) LYMPHOMA

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

Breast cancer

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

ALLOGENEIC HPCT

Haematological diseases

The recommended dose in haematological diseases ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 2 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.

LYMPHOMA

The recommended dose in lymphoma is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.

LEUKAEMIA

The recommended dose ranges from 185 mg/m2/day (5 mg/kg/day) to 370 mg/m2/day (10 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 2 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.

Paediatric population

AUTOLOGOUS HPCT

CNS TUMOURS

The recommended dose ranges from 200 mg/m2/day (8 mg/kg/day) to 300 mg/m2/day (12 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 900 mg/m2 (36 mg/kg), during the time of the entire conditioning treatment.

ALLOGENEIC HPCT

Haematological diseases

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

LEUKAEMIA

The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.

THALASSEMIA

The recommended dose ranges from 200 mg/m2/day (8 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.

REFRACTORY CYTOPENIA

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

GENETIC DISEASES

The recommended dose ranges from 125 mg/m2/day (5 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) as a single daily infusion or administered for 2 consecutive days before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.

SICKLE CELL ANAEMIA

The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.

Special populations

Renal impairment

Studies in renally impaired patients have not been conducted. As thiotepa and its metabolites are poorly excreted in the urine, dose modification is not recommended in patients with mild or moderate renal insufficiency. However, caution is recommended (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

Thiotepa has not been studied in patients with hepatic impairment. Since thiotepa is mainly metabolized through the liver, caution needs to be exercised when thiotepa is used in patients with pre-existing impairment of liver function, especially in those with severe hepatic impairment. Dose modification is not recommended for transient alterations of hepatic parameters (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elderly

The administration of thiotepa has not been specifically investigated in elderly patients. However, in clinical studies, a proportion of patients over the age of 65 received the same cumulative dose as the other patients. No dose adjustment was deemed necessary.

Method of administration

TEPADINA must be administered by a qualified healthcare professional as a 2–4 hours intravenous infusion via a central venous catheter.

Each vial must be reconstituted with 1.5 mL (TEPADINA 15 mg) or 10 mL (TEPADINA 100 mg) of sterile water for injections. The total volume of reconstituted vials to be administered should be further diluted in 500 mL of sodium chloride 9 mg/mL (0.9%) solution for injection prior to administration (1 000 mL if the dose is higher than 500 mg). In children, if the dose is lower than 250 mg, an appropriate volume of sodium chloride 9 mg/mL (0.9%) solution for injection may be used in order to obtain a final TEPADINA concentration between 0.5 and 1 mg/mL. For instructions on reconstitution and further dilution prior to administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Precautions to be taken before handling or administering the medicinal product

Topical reactions associated with accidental exposure to thiotepa may occur. Therefore, the use of gloves is recommended in preparing the solution for infusion. If thiotepa solution accidentally contacts the skin, the skin must be immediately thoroughly washed with soap and water. If thiotepa accidentally contacts mucous membranes, they must be flushed thoroughly with water (see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).