Vision Abnormal * 8 (5)
*Blurred vision, visual deficit, vision changes, vision troubles.
Table 4 Adverse Hematologic Effects (Grade 3 to 4) in the
Anaplastic Astrocytoma Trial in Adults
TEMODAR a
Hemoglobin 7/158 (4%)
Lymphopenia 83/152 (55%)
Neutrophils 20/142 (14%)
Platelets 29/156 (19%)
WBC 18/158 (11%)
a Change from Grade 0 to 2 at baseline to Grade 3 or 4 during treatment.
In addition, the following spontaneous adverse experiences have been reported during the marketing surveillance of TEMODAR Capsules: allergic reactions, including rare cases of anaphylaxis. Rare cases of erythema multiforme have been reported which resolved after discontinuation of TEMODAR and, in some cases, recurred upon rechallenge. Rare cases of opportunistic infections including Pneumocystis carinii pneumonia (PCP) have also been reported.
OVERDOSAGE
Doses of 500, 750, 1000, and 1250 mg/m 2 (total dose per cycle over 5 days) have been eva luated clinically in patients. Dose-limiting toxicity was hematologic and was reported with any dose but is expected to be more severe at higher doses. An overdose of 2000 mg per day for 5 days was taken by one patient and the adverse events reported were pancytopenia, pyrexia, multi-organ failure and death. There are reports of patients who have taken more than 5 days of treatment (up to 64 days) with adverse events reported including bone marrow suppression, which in some cases was severe and prolonged, and infections and resulted in death. In the event of an overdose, hematologic eva luation is needed. Supportive measures should be provided as necessary.
DOSAGE AND ADMINISTRATION
Dosage of TEMODAR Capsules must be adjusted according to nadir neutrophil and platelet counts in the previous cycle and the neutrophil and platelet counts at the time of initiating the next cycle.
For TEMODAR dosage calculations based on body surface area (BSA) see Table 9 . For suggested capsule combinations on a daily dose see Table 10 .
Patients with Newly Diagnosed High Grade Glioma:
Concomitant Phase
TEMODAR is administered orally at 75 mg/m 2 daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions) followed by maintenance TEMODAR for 6 cycles. Focal RT includes the tumor bed or resection site with a 2-3 cm margin. No dose reductions are recommended during the concomitant phase; however, dose interruptions or discontinuation may occur based on toxicity. The TEMODAR dose should be continued throughout the 42 day concomitant period up to 49 days if all of the following conditions are met: absolute neutrophil count >/= 1.5 × 10 9 /L platelet count >/= 100 × 10 9 /L common toxicity criteria (CTC) non-hematological toxicity </= Grade 1 (except for alopecia, nausea and vomiting). During treatment a complete blood count should be obtained weekly. Temozolomide dosing should be interrupted or discontinued during concomitant phase according to the hematological and non-hematological toxicity criteria as noted in Table 5 . PCP prophylaxis is required during the concomitant administration of TEMODAR and radiotherapy and should be continued in patients who develop lymphocytopenia until recovery from lymphocytopenia (CTC grade </= 1).
Table 5 |
