Overview
11 DESCRIPTION Temozolomide is an alkylating drug. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]- as -tetrazine-8-carboxamide. The structural formula of temozolomide is: The material is a white to light tan or light pink powder with a molecular formula of C 6 H 6 N 6 O 2 and a molecular weight of 194.15.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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 DNA alkylation, mainly at the O 6 and N 7 positions of guanine, which causes DNA double strand breaks and results in programmed cell death. 12.2 Pharmacodynamics Temozolomide exposure-response relationships and the time course of pharmacodynamic response are unknown. 12.3 Pharmacokinetics Following a single oral dose of 150 mg/m 2 , the mean C max is 7.5 mcg/mL for temozolomide and 282 ng/mL for MTIC. The mean AUC is 23.4 mcg∙hr/mL for temozolomide and 864 ng∙hr/mL for MTIC.
Indications
- 1 INDICATIONS AND USAGE TEMODAR is an alkylating drug indicated for the treatment of adults with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. ( 1.1 ) Anaplastic astrocytoma. ( 1.2 ) Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma. ( 1.2 ) Treatment of adults with refractory anaplastic astrocytoma. ( 1.2 ) 1.1 Newly Diagnosed Glioblastoma TEMODAR is indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment. 1.
Common Doses
- 75 mg
- 150 mg
- 200 mg
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION Administer either orally or intravenously. ( 2.4 ) Newly Diagnosed Glioblastoma : 75 mg/m 2 once daily for 42 to 49 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m 2 once daily for Days 1 to 5 of each 28-day cycle for 6 cycles. May increase maintenance dose to 200 mg/m 2 for Cycles 2 to 6 based on toxicity. ( 2.1 ) Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less. ( 2.
Contraindications
- 4 CONTRAINDICATIONS TEMODAR is contraindicated in patients with a history of serious hypersensitivity reactions to: temozolomide or any other ingredients in TEMODAR; and dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to TEMODAR have included anaphylaxis [see Adverse Reactions (6.2) ]. History of serious hypersensitivity to temozolomide or any other ingredients in TEMODAR and dacarbazine. ( 4 )
Side Effects
- 6 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) ] The most common adverse reactions (≥20%) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions. ( 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.