Indication

TEMODAR (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

Select Important Safety Information

TEMODAR is contraindicated in patients who have a history of hypersensitivity (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components, or to DTIC.

Patients 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. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have also been observed.

Prophylaxis against Pneumocystis carinii pneumonia 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.

TEMODAR can cause fetal harm when administered to a pregnant woman. In nursing women, a decision should be made whether to discontinue nursing or to discontinue TEMODAR, taking into account the importance of the drug to the mother. The safety and effectiveness of TEMODAR in children have not been established.

As bioequivalence between TEMODAR Capsules and TEMODAR for Injection 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.

TEMODAR Capsules should not be opened or chewed. If capsules are accidentally opened or damaged, rigorous precautions should be taken with the capsule contents to avoid inhalation or contact with the skin or mucous membranes.

Caution should be exercised when administered to those with severe hepatic or renal impairment.

The adverse event profile was similar in patients <65 years of age and those ≥65 years.

The most common adverse reactions in clinical studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were alopecia 69%, 55%; fatigue 54%, 61%; nausea 36%, 49%; vomiting 20%, 29%; anorexia 19%, 27%; headache 19%, 23%; rash 19%, 13%; constipation 18%, 22%; with the following important adverse events also reported: convulsions 6%, 11% and thrombocytopenia 4%, 8%.

Of these adverse events, those grade ≥3 in clinical studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were fatigue 7%, 9%; nausea 1%, 1%; vomiting <1%, 2%; anorexia 1%, 1%; headache 2%, 4%; rash 1%, 1%; constipation 1%, 0%; convulsions 3%, 3%; thrombocytopenia 3%, 4%.

When laboratory abnormalities and adverse events were combined, Grade 3 or 4 neutropenia occurred in 8% and Grade 3 or 4 platelet abnormalities, including thrombocytopenic events, occurred in 14% of patients treated with temozolomide.

Adverse reactions reported from intravenous formulation studies that were not reported in TEMODAR Capsule studies were: pain, irritation, pruritus, warmth, swelling, and erythema at infusion site as well as the following adverse reactions: petechiae and hematoma.