Temozolomide (Temodar and Temodal) is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma
Antineoplastic Agents Immunosuppressive Agents Antineoplastic Agents, Alkylating Alkylating Agents Antineoplastic and Immunomodulating Agents CYP3A4 Inhibitors
Temozolomide 20 MG
For the treatment of adult patients diagnosed with anaplastic astrocytoma whose disease has progressed after therapy with nitrosourea and procarbazine, as well as concomitantly with radiation therapy for treatment of newly diagnosed glioblastoma multiforme. Also used as maintenance therapy for glioblastoma multiforme.
Temozolomide is an imidazotetrazine deritave and an antineoplastic agent. It is a prodrug that has little to no pharmacological activity until it is hydrolyzed in vivo to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC). After administration, temozolomide undergoes rapid, nonenzymatic hydrolysis at physiological pH to MTIC, which is the active form of the drug. MTIC is generated through the effect of water at the highly electropositive C4 position of temozolomide, causing the ring of temozolomide to open, release carbon dioxide, and generate MTIC.
Temozolomide is not active until it is converted at physiologic pH to MTIC. It is suggested that MTIC then alkylates DNA at the N7 position of guanine, O3 position of adenosine, and O6 position of guanosine, with the most common site being the N7 position. This methylation of guanine residues lead to single and double-strand DNA breaks and subsequent apoptotic cell death. It is suggested that the N7-methylguanine plays a critical role in the antitumor activity of the drug, as there is a correlation between the sensitivity of tumor cell lines to temozolomide and the activity of O6-alkylguanine alkyltransferase, which is the DNA repair protein that specifically removes alkyl groups at the O6 position of guanine. Cells lines that have lower levels of AGT are more sensitive to the cytotoxicity of temozolomide. It is also suggested that cytotoxic mechanism of temozolomide is related to the failure of the DNA MMR system to find a complementary base for methylated guanine. The DNA MMR system is involved in the formation of a number of proteins that remove methylated guanine. Evidence shows that when this repair process is targeted to the DNA strand opposite the O6-methylguanine, its inability to find the correct target leads to long-lived nicks in the DNA. The accumulation of these nicks lead to the inhibition of replication in the daughter cells, thereby blocking the cell cycle at the G2-M boundary.
Rapid and complete absorption in the gastrointestinal tract
About 38% of the administered temozolomide total radioactive dose is recovered over 7 days: 37.7% in urine and 0.8% in feces.
Approximately 1.8 hours.
Chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Headache. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. You may need drugs to lower this side effect. Talk with your doctor. Hard stools (constipation). Drinking more liquids, working out, or adding fiber to your diet may help. Talk with your doctor about a stool softener or laxative. Loose stools (diarrhea). Swelling in the arms or legs. Hair loss. Hair most often grows back when this drug is stopped. Feeling tired or weak. Not hungry. Low white blood cell count or low platelet count. Irritation where the shot is given.