TEMODAR- temozolomide capsule
TEMODAR- temozolomide injection, powder, lyophilized, for solution
Merck Sharp & Dohme Corp.
1 INDICATIONS AND USAGE1.1 Newly Diagnosed Glioblastoma MultiformeTEMODAR® (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.
1.2 Refractory Anaplastic AstrocytomaTEMODAR is indicated for the treatment of adult patients with refractory anaplastic astrocytoma, i.e., patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.
2 DOSAGE AND ADMINISTRATION2.1 Recommended Dosing and Dose Modification GuidelinesThe recommended dose for TEMODAR as an intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes [see Clinical Pharmacology (12.3)]. Dosage of TEMODAR 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 5. For suggested capsule combinations on a daily dose see Table 6.
Patients with Newly Diagnosed High Grade Glioma:
Concomitant Phase:
TEMODAR is administered at 75 mg/m2 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- to 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 greater than or equal to 1.5 × 109 /L, platelet count greater than or equal to 100 × 109 /L, common toxicity criteria (CTC) nonhematological toxicity less than or equal to 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 nonhematological toxicity criteria as noted in Table 1. Pneumocystis carinii pneumonia (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 less than or equal to 1).
TABLE 1: Temozolomide Dosing Interruption or Discontinuation During Concomitant Radiotherapy and Temozolomide Toxicity TMZ Interruption * TMZ Discontinuation
TMZ=temozolomide; CTC=Common Toxicity Criteria.
* Treatment with concomitant TMZ could be continued when all of the following conditions were met: absolute neutrophil count greater than or equal to 1.5 × 109 /L; platelet count greater than or equal to 100 × 109 /L; CTC nonhematological toxicity less than or equal to Grade 1 (except for alopecia, nausea, vomiting).
Absolute Neutrophil Count greater than or equal to 0.5 and less than 1.5 × 109 /L less than 0.5 × 109 /L
Platelet Count greater than or equal to 10 and less than 100 × 109 /L less than 10 × 109 /L
CTC Nonhematological Toxici