ion is not recommended for transient alterations of hepatic parameters (see section 4.4).
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 TEPADINA vial must be reconstituted with 1.5 ml of sterile water for injection. 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.
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).
4.3 Contraindications
Hypersensitivity to the active substance.
Pregnancy and lactation (see section 4.6).
Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines (see section 4.5).
4.4 Special warnings and precautions for use
The consequence of treatment with thiotepa at the recommended dose and schedule is profound myelosuppression, occurring in all patients. Severe granulocytopenia, thrombocytopenia, anaemia or any combination thereof may develop. Frequent complete blood counts, including differential white blood cell counts, and platelet counts need to be performed during the treatment and until recovery is achieved. Platelet and red blood cell support, as well as the use of growth factors such as Granulocyte-colony stimulating factor (G-CSF), should be employed as medically indicated. Daily white blood cell counts and platelet counts are recommended during therapy with thiotepa and after transplant for at least 30 days.
Prophylactic or empiric use of anti-infectives (bacterial, fungal, viral) should be considered for the prevention and management of infections during the neutropenic period.
Thiotepa has not been studied in patients with hepatic impairment. Since thiotepa is mainly metabolized through the liver, caution needs to be observed when thiotepa is used in patients with pre-existing impairment of liver function, especially in those with severe hepatic impairment. When treating such patients it is recommended that serum transaminase, alkaline phosphatase and bilirubin are monitored regularly following transplant, for early detection of hepatotoxicity.
Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or prior progenitor cell transplant may be at an increased risk of hepatic veno-occlusive disease (see section 4.8).
Caution must be used |
