Description

Thiotepa 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 solid tumours in adult and paediatric patients.

Hypersensitivity to the active substance. Pregnancy and lactation. Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines.

There are no data on the use of thiotepa during pregnancy. In pre-clinical studies thiotepa, as most alkylating agents, has been shown to cause embryofoetal lethality and teratogenicity. Therefore, thiotepa is contraindicated during pregnancy. It is unknown whether thiotepa is excreted in human milk. Due to its pharmacological properties and its potential toxicity for breast-fed newborns/infants, breastfeeding is contraindicated during treatment with thiotepa.

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.

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. 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. 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.

There is no experience with overdoses of thiotepa. The most important adverse reactions expected in case of overdose is myeloablation and pancytopenia. There is no known antidote for thiotepa. The haematological status needs to be closely monitored and vigorous supportive measures instituted as medically indicated.

Haematopoietic Agents