atients treated with TEMODAR may experience myelosuppression, including prolonged pancytopenia, which may result in aplastic anemia, which in some cases has resulted in a fatal outcome. In some cases, exposure to concomitant medications associated with aplastic anemia, including carbamazepine, phenytoin, and sulfamethoxazole/trimethoprim, complicates assessment. Prior to dosing, patients must have an absolute neutrophil count (ANC) greater than or equal to 1.5 × 109 /L and a platelet count greater than or equal to 100 × 109 /L. A complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 109 /L and platelet count exceeds 100 × 109 /L. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression.
5.2 Myelodysplastic Syndrome
Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed.
5.3 Pneumocystis carinii Pneumonia
For treatment of newly diagnosed glioblastoma multiforme: Prophylaxis against Pneumocystis carinii pneumonia (PCP) is required for all patients receiving concomitant TEMODAR and radiotherapy for the 42-day regimen.
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.
5.4 Laboratory TestsFor the concomitant treatment phase with RT, a complete blood count should be obtained prior to initiation of treatment and weekly during treatment.
For the 28-day treatment cycles, a complete blood count should be obtained prior to treatment on Day 1 and on Day 22 (21 days after the first dose) of each cycle. Blood counts should be performed weekly until recovery if the ANC falls below 1.5 × 109 /L and the platelet count falls below 100 × 109 /L [see Recommended Dosing and Dose Modification Guidelines (2.1)].
5.5 Use in PregnancyTEMODAR can cause fetal harm when administered to a pregnant woman. Administration of TEMODAR to rats and rabbits during organogenesis at 0.38 and 0.75 times the maximum recommended human dose (75 and 150 mg/m2), respectively, caused numerous fetal malformations of the external organs, soft tissues, and skeleton in both species [see Use in Specific Populations (8.1)].
5.6 Infusion TimeAs bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes, infusion over a shorter or longer period of time may result in suboptimal dosing. Additionally, the possibility of an increase in infusion-related adverse reactions cannot be ruled out.
6 ADVERSE REACTIONS6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Newly Diagnosed Glioblastoma Multiforme:
During the concomitant phase (TEMODAR+radiotherapy), adverse reactions including thrombocytopenia, nausea, vomiting, anorexia, and constipation were more frequent in the TEMODAR+RT arm. The incidence of other adverse reactions was comparable in the two arms. The most common adverse reactions across the cumulative TEMODAR experience were a |
