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

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**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_).