al disorders
Nausea
Stomatitis
Vomiting
Diarrhoea
Abdominal pain
Enteritis
Intestinal obstruction
Hepatobiliary disorders
Venoocclusive liver disease
Liver failure
Skin and subcutaneous tissue disorders
Rash
Erythema
Desquamation
Pigmentation disorder
Severe toxic skin reactions including cases of Stevens-Johnson syndrome and toxic epidermal necrolysis
Musculoskeletal and connective tissue disorders
Growth retardation
Renal and urinary disorders
Bladder disorders
Renal failure
Cystitis haemorrhagic
General disorders and administration site conditions
Pyrexia
Mucosal inflammation
Pain
Multi-organ failure
Investigation
Blood bilirubin increased
Transaminases increased
Blood creatinine increased
Aspartate aminotransferase increased
Alanine aminotransferase increased
Blood urea increased
Blood electrolytes abnormal
Prothrombin time ratio increased
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
4.9 Overdose
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.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antineoplastic agents, Alkylating Agents, ATC code: L01AC01
Mechanism of action
Thiotepa is a polyfunctional cytotoxic agent related chemically and pharmacologically to the nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylene imine radicals that, as in the case of irradiation therapy, disrupt the bonds of DNA, e.g. by alkylation of guanine at the N-7, breaking the linkage between the purine base and the sugar and liberating alkylated guanine.
Clinical safety and efficacy
The conditioning treatment must provide cytoreduction and ideally disease eradication. Thiotepa has marrow ablation as its dose-limiting toxicity, allowing significant dose escalation with the infusion of autologous HPCT. In allogeneic HPCT, the conditioning treatment must be sufficiently immunosuppressive and myeloablative to overcome host rejection of the graft. Due to its highly myeloablative characteristics, thiotepa enhances recipient immunosuppression and myeloablation, thus strengthening engraftment; this compensates for the loss of the GvHD-related GvL effects. As alkylating agent, thiotepa produces the most profound inhibition of tumour cell growth in vitro with the smallest increase in medicinal product concentration. Due to its lack of extramedullary toxicity despite dose escalation beyond myelotoxic doses, thiotepa has been used for decades in combination with other chemotherapy medicinal products prior to autologous and allogeneic HPCT.
The results of published clinical studies support |
