Special Warning : אזהרת שימוש

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 in patients with history of cardiac diseases, and cardiac function must be monitored regularly in patients receiving thiotepa.

Caution must be used in patients with history of renal diseases and periodic monitoring of renal function should be considered during therapy with thiotepa.

Thiotepa might induce pulmonary toxicity that may be additive to the effects produced by other cytotoxic agents (busulfan, fludarabine and cyclophosphamide) (see section 4.8).

Previous brain irradiation or craniospinal irradiation may contribute to severe toxic reactions (e.g. encephalopathy).

The increased risk of a secondary malignancy with thiotepa, a known carcinogen in humans, must be explained to the patient.

Concomitant use with live attenuated vaccines (except yellow fever vaccines), phenytoin and fosphenytoin is not recommended (see section 4.5).
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 (see section 4.5).

During the concomitant use of thiotepa and inhibitors of CYP2B6 or CYP3A4, patients should be carefully monitored clinically (see section 4.5).

As most alkylating agents, thiotepa might impair male or 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 4.6).

Effects on Driving

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.