Temozolomide

What it is and how it works

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 O 6 and N 7 positions of guanine.

Mechanism class: Alkylating Activity

Indications

1. INDICATIONS AND USAGE TEMOZOLOMIDE Capsules, USP are an alkylating drug indicated for the treatment of adult patients with: • Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. • Refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine. Newly Diagnosed Glioblastoma TEMOZOLOMIDE Capsules, USP is indicated for the treatment of adult patients with newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. Refractory Anaplastic Astrocytoma TEMOZOLOMIDE Capsules , USP is indicated for the treatment of adult patients with refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

Dosage and administration (summary)

2. DOSAGE AND ADMINISTRATION Administer either orally or intravenously. Newly Diagnosed Glioblastoma: o 75 mg/m 2 once daily for 42 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 – 6 based on toxicity. o Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to grade 1 or less. Refractory Anaplastic Astrocytoma: Initial dose of 150 mg/m 2 once daily on Days 1 to 5 of each 28-day cycle.

Contraindications

4. 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 . History of hypersensitivity to temozolomide or any other ingredients in TEMOZOLOMIDE capsules, USP and dacarbazine.

Warnings and precautions

5. WARNINGS AND PRECAUTIONS Myelosuppression: Monitor absolute neutrophil count (ANC) and platelet count prior to each cycle and during treatment. Geriatric patients and women have a higher risk of developing myelosuppression. Myelodysplastic Syndrome and Secondary Malignancies , including myeloid leukemia, have been observed. Pneumocystis Pneumonia (PCP): Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP. Hepatotoxicity: Fatal and severe hepatotoxicity have been reported.

Pregnancy

Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, TEMOZOLOMIDE can cause fetal harm when administered to a pregnant woman. Available postmarketing reports describe cases of spontaneous abortions and congenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, a…

Storage and supply

16. HOW SUPPLIED/STORAGE AND HANDLING TEMOZOLOMIDE is a cytotoxic drug. Follow applicable special handling and disposal procedures. TEMOZOLOMIDE Capsules, USP are supplied in amber glass bottles, with child-resistant polypropylene caps (not supplied in sachets) containing the following capsule strengths: TEMOZOLOMIDE Capsules USP, 5 mg: Have opaque…

Source: Temozolomide (Temozolomide) — US FDA prescribing information, 2025-01-09, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.