II. Indications
- FDA Approved
- Anaplastic Astrocytoma
- Glioblastoma Multiforme
- Off Label (typically recurrent or refractory neoplasms)
- Cutaneous T Cell Lymphoma
- Ewing Sarcoma
- Lymphoma (CNS)
- Metastatic Melanoma
- Neuroblastoma (children)
- Neuroendocrine Tumors (e.g. Carcinoid Tumor)
- Renal Cell Carcinoma
- Soft Tissue Sarcoma
III. Mechanism
- See Alkylating Agent
- Triazene Alkylating Agent, an analog of Dacarbazine
- Temozolomide is a prodrug activated at physiologic pH to MTIC (monomethyl triazeno imidazole carboxamide)
- Contrast with Dacarbazine which is only metabolized to active MTIC in the liver
- MTIC methylates DNA at guanine's O6 and N7
- Inhibits DNA Replication
- Similar activity to Dacarbazine
IV. Medications
- Capsule: Various from 5 mg to 250 mg
- Lyophilized injection powder for IV Solution: 100 mg
V. Dosing
- See other references for disease specific dosing protocols
VI. Pharmacokinetics
- Good CNS penetration
VII. Adverse Effects
- Alopecia
- Bone Marrow Suppression
- Secondary Malignancy
- Impaired future fertility
- Respiratory (interstitial pneumonitis, pulmonary fibrosis)
- Opportunistic infections (CMV, Hepatitis B)
VIII. Safety
- Avoid in Lactation
- Avoid in Pregnancy (all trimesters)
- Use reliable Contraception
- Monitoring
IX. Drug Interactions
-
Valproic Acid
- Raises Temozolomide levels by decreasing clearance
X. Resources
XI. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Wesolowski (2010) AJNR Am J Neuroradiol 31(8):1383-4 +PMID: 20538821 [PubMed]