tion of therapy and vaccination.
Concomitant use not recommended
Live attenuated vaccines (except yellow fever): risk of systemic, possibly fatal disease. This risk is increased in subjects who are already immunosuppressed by their underlying disease.
An inactivated virus vaccine should be used instead, whenever possible (poliomyelitis).
Phenytoin: risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic medicinal product or risk of toxicity enhancement and loss of efficacy of the cytotoxic medicinal product due to increased hepatic metabolism by phenytoin.
Concomitant use to take into consideration
Ciclosporine, tacrolimus: excessive immunosuppression with risk of lymphoproliferation.
Alkylating chemotherapeutic agents, including thiotepa, inhibit plasma pseudocholinesterase by 35% to 70%. The action of succinyl-choline can be prolonged by 5 to 15 minutes.
Thiotepa must not be concurrently administered with cyclophosphamide when both medicinal products are present in the same conditioning treatment. TEPADINA must be delivered after the completion of any cyclophosphamide infusion.
The concomitant use of thiotepa and other myelosuppressive or myelotoxic agents (i.e. cyclophosphamide, melphalan, busulfan, fludarabine, treosulfan) may potentiate the risk of haematologic adverse reactions due to overlapping toxicity profiles of these medicinal products.
Interaction common to all cytotoxics
Due to the increase of thrombotic risk in case of malignancy, the use of anticoagulative treatment is frequent. The high intra-individual variability of the coagulation state during malignancy, and the potential interaction between oral anticoagulants and anticancer chemotherapy require, if it is decided to treat the patient with oral anticoagulants, to increase the frequency of the INR (International Normalised Ratio) monitoring.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential have to use effective contraception during treatment and a pregnancy test should be performed before treatment is started.
Pregnancy
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 (see section 5.3). Therefore, thiotepa is contraindicated during pregnancy.
Breast-feeding
It is unknown whether thiotepa is excreted in human milk. Due to its pharmacological properties and its potential toxicity for breast-fed newborns/infants, breast-feeding is contraindicated during treatment with thiotepa.
Fertility
As most alkylating agents, thiotepa might impair male and female fertility.
Male patients should seek for sperm cryopreservation before therapy is started and should not father a child while treated and during the year after cessation of treatment (see section 5.3).
4.7 Effects on ability to drive and use machines
TEPADINA may have major influence on the ability to drive and use machines. It is likely that certain adverse reactions of thiotepa like dizziness, headache and blurred vision could affect these functions.
4.8 Undesirable effects
Summary of the safety profile
The safety of thiotepa has been examined through a review of adverse events reported in published data from clinical trials. In these studies, a total of 6,588 adult patients and 902 paediatric patients re |
