Temozolomide (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: POWDER, CAPSULE.
Routes of administration: INTRAVENOUS, ORAL.
Brand Names
- TEMODAR
- TEMOZOLOMIDE
Contraindications
TEMOZOLOMIDE is contraindicated in patients with a history of hypersensitivity reactions to: • temozolomide or any other ingredients in TEMOZOLOMIDE; and • dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to TEMOZOLOMIDE have included anaphylaxis [see Adverse Reactions ( 6.2 )].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1)]. Hepatotoxicity [see Warnings and Precautions (5.2)]. Pneumocystis Pneumonia [see Warnings and Precautions (5.3)]. Secondary Malignancies[see Warnings and Precautions (5.4)].
Mechanism of Action
Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA. Alkylation (methylation) occurs mainly at the O6 and N7 positions of guanine.
Overdosage
Dose-limiting toxicity was myelosuppression 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 myelosuppression, which in some cases was severe and prolonged, and infections and resulted in death. In the event of an overdose, monitor complete blood count and provide supportive measures as necessary.