It is an alkylating drug indicated for the treatment of adult patients with: ? Newly diagnosed glioblastoma multiforme (GBM) concomitantly with radiotherapy and then as maintenance treatment. ? Refractory anaplastic astrocytoma patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.
Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound Methyl Triazen Imidazole Carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA. Alkylation (methylation) occurs mainly at the 0 6 and N 7 positions of guanine.
Newly Diagnosed GBM: 75 mg/m2 for 42 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m2 once daily for Days 1-5 of a 28-day cycle of It for 6 cycles. ? Refractory Anaplastic Astrocytoma: Initial dose 150 mg/m2 once daily for 5 consecutive days per 28-day treatment cycle. ? The recommended dose for It as an intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when It for Injection was given over 90 minutes.
Valproic Acid: Administration of valproic acid decreases oral clearance of temozolomide by about 5%. The clinical implication of this effect is not known.
Known hypersensitivity to any It component or to dacarbazine (DTIC).
Alopecia,fatigue,nausea,vomiting,headache,constipation, anorexia,convulsions,rash,hemiparesis,diarrhea,asthenia, fever,dizziness,coordination abnormal,viral infection,amnesia, and insomnia.
Nursing mothers: Not recommended. Pediatric use: No established use
Doses of 500, 750, 1000, and 1250 mg/m2 (total dose per cycle over 5 days) have been evaluated 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 reactions 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 reactions 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 evaluation is needed. Supportive measures should be provided as necessary.
Store at a temperature not exceeding 25°C in a dry place. Protect from light and moisture. Do not freeze.
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