Temozolomide is an oral alkylating agent of the imidazotetrazine class, used primarily in the treatment of specific malignant gliomas. It is a prodrug that undergoes rapid non-enzymatic conversion at physiological pH to the active metabolite MTIC (3-methyl-(triazen-1-yl)imidazole-4-carboxamide). Its lipophilic nature allows it to cross the blood-brain barrier effectively, making it a cornerstone in neuro-oncology, particularly for glioblastoma multiforme (GBM). In India, it is a critical component of the Stupp protocol (concomitant and adjuvant therapy with radiotherapy).
Adult: **Newly diagnosed GBM (Stupp Protocol):** 75 mg/m² orally daily for 42 days concomitantly with focal radiotherapy, followed by a 4-week break, then 6 cycles of adjuvant therapy: 150-200 mg/m² orally daily for 5 days, repeated every 28 days. **Refractory Anaplastic Astrocytoma:** Initial dose: 150 mg/m² orally daily for 5 days, repeated every 28 days. Cycle 2 onwards: May be increased to 200 mg/m²/day for 5 days if nadir counts meet criteria.
Note: Swallow capsule whole with a full glass of water, on an empty stomach (at least 1 hour before and 2 hours after food). Do not open, chew, or crush capsules. If capsule is damaged, avoid direct contact with skin or mucous membranes. Administer at the same time each day during a treatment cycle. For the concomitant phase with RT, administer temozolomide 1 hour prior to radiotherapy.
Temozolomide is a prodrug that undergoes spontaneous hydrolysis at physiological pH to form the reactive compound MTIC. MTIC further decomposes to release a methyldiazonium ion. This highly electrophilic cation is the ultimate alkylating species responsible for transferring methyl groups to nucleophilic sites on DNA. The primary cytotoxic lesion is the methylation of the O6 position of guanine. If not repaired by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), this mismatch leads to futile cycles of mismatch repair (MMR), ultimately triggering DNA double-strand breaks and apoptosis.
Pregnancy: **Pregnancy Category D.** Based on animal data and mechanism, can cause fetal harm. May cause teratogenicity and embryolethality. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy. Men with female partners of childbearing potential should use condoms during and for at least 3 months after therapy.
Driving: May cause fatigue, dizziness, and somnolence. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| Valproic Acid | May decrease temozolomide clearance by ~5%, potentially increasing exposure. Clinical significance uncertain but monitor for increased toxicity. | Moderate |
| Strong CYP450 Inducers (e.g., Carbamazepine, Phenytoin, Rifampicin) | Potential to increase the conversion rate of temozolomide to MTIC, but clinical impact on efficacy/toxicity is not well established. Monitor efficacy. | Moderate |
| Live Vaccines | Increased risk of vaccine-induced infection due to immunosuppression. Contraindicated. | Major |
| Other Myelosuppressive Agents (e.g., Clozapine, other chemotherapy) | Additive risk of severe bone marrow suppression. Avoid concurrent use or monitor blood counts very closely. | Major |