Temodal Special Precautions

Patients who received concomitant TEMODAL and radiotherapy in a pilot trial for the prolonged 42-day schedule were shown to be at particular risk for developing Pneumocystis carinii pneumonia. Thus, prophylaxis against Pneumocystis carinii pneumonia is required for all patients receiving concomitant TEMODAL and radiotherapy for the 42-day regimen (with a maximum of 49 days). There may be a higher occurrence of PCP when temozolomide is administered during a longer dosing regimen. However, all patients receiving temozolomide, particularly patients receiving steroids should be observed closely for the development of PCP regardless of the regimen.
Antiemetic therapy: Nausea and vomiting are very commonly associated with TEMODAL, and guidelines are provided.
Patients with newly diagnosed glioblastoma multiforme: Antiemetic prophylaxis is recommended prior to the initial dose of concomitant temozolomide. Antiemetic prophylaxis is strongly recommended during the adjuvant phase.
Patients with recurrent or progressive glioma: Patients who have experienced severe (Grade 3 or 4) vomiting in previous treatment cycles may require antiemetic therapy.
All Patients: Use in patients with hepatic or renal impairment: The pharmacokinetics of TEMODAL were comparable in patients with normal hepatic function and in those with mild or moderate hepatic impairment. No data are available on the administration of TEMODAL in patients with severe hepatic impairment (Child-Pugh grade C) or with renal impairment. Based on the pharmacokinetic properties of TEMODAL, it is unlikely that dose reductions are required in patients with severe hepatic impairment or any degree of renal impairment. However, caution should be exercised when TEMODAL is administered in these patients.
Hepatotoxicity: Hepatic injury, including fatal hepatic failure, has been reported in patients treated with TEMODAL. Baseline liver function tests should be performed prior to treatment initiation. If abnormal, physicians should assess the benefit/risk prior to initiating temozolomide including the potential for fatal hepatic failure. For patients on a 42-day treatment cycle, liver function tests should be repeated midway during this cycle. For all patients, liver function tests should be checked after each treatment cycle. For patients with significant liver function abnormalities, physicians should assess the benefit/risk of continuing treatment. Liver toxicity may occur several weeks or more after the last treatment with temozolomide.
Additionally, hepatitis due to hepatitis B virus (HBV) reactivation, in some cases resulting in death, has been reported. Patients should be screened for HBV infection before treatment initiation. Patients with evidence of prior HBV infection should be monitored for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment with TEMODAL. Therapy should be discontinued for patients with evidence of active hepatitis B infection.
Use in Children: There is no clinical experience with use of TEMODAL in children under the age of 3 years. Experience in older children and adolescents is very limited.
Use in the Elderly: Elderly patients (>70 years of age) appear to be at increased risk of neutropenia and thrombocytopenia, compared with younger patients.