Temozolomide is an imidazotetrazine derivative, the chemical name is 3, 4- dihydro- 3- methyl- 4- oxoimidazo [5, 1- d]- as- tetrazine- 8- carboxamide.It has a molecular weight of 194.15. The molecule is stable at acidic pH ( < 5) and labile at pH > 7; hence it can be administered orally and intravenously. The prodrug, temozolomide, is rapidly hydrolyzed to the active 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) at neutral and alkaline pH values, with hydrolysis taking place even faster at alkaline pH.
Each capsule contains Temozolomide INN 100 mg and 250 mg.
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 O6 and N7 positions of guanine.
Protein Binding: 15%.
Half Life: Approximately 1.8 hours
Excretion: 37.7% in urine and 0.8% in feces
Zolomide® is used to treat Glial Tumors, Brain Metastasis, Ewing’s Tumors, Malignant Melanoma and Neuroendocrine Tumors.
Dosage and administration
Glial Tumors: 150-200 mg/m2 (d 1-5) repeated every 4 weeks or 75 mg/m2/d for 6 weeks followed by 6 weeks radiotherapy followed by 150-200 mg/m2 (d 1-5) repeated every 4 weeks for 6 cycle.
Brain Metastasis: 150 mg/m2 (d 1-7, 15-21) or 150-200 mg/m2 (d 1-5) or 75 mg/m2/d during radiotherapy and 200 mg/m2 d 1-5, repeated every 4 weeks.
Ewing’s Tumors: 100 mg/m2 (d 1-5) repeated every 3 weeks, given in combination with Irinotecan.
Malignant Melanoma: 200 mg/m2(d 1-5) repeated every 4 weeks, given in combination with Interferon alpha.
Neuroendocrine Tumors: 150 mg/m2 (d 1-7, 15-21) repeated every 4 weeks, given in combination with Thalidomide.
To reduce nausea and vomiting, Temozolomide should be taken on an empty stomach. Bedtime administration may be advised. Antiemetic therapy may be administered prior to and/or following administration of Temozolomide. Temozolomide Capsules should not be opened or chewed. They should be swallowed whole with a glass of water.
Possible side effects
Seizure (convulsions),numbness or tingling on one side of your body; signs of infection such as fever, chills, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), loss of appetite, nausea and vomiting, unusual weakness; dry cough are common side effects of Zolomide®
Zolomide® is contraindicated in patients who have a history of hypersensitivity reaction (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components. Zolomide® is also contraindicated in patients who have a history of hypersensitivity to DTIC, since both drugs are metabolized to 5-(3-methyltriazen-1-yl)-imidazole 4-carboxamide (MTIC).
Pregnancy Category D, Temozolomide can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Temozolomide.
Valproic Acid: Administration of valproic acid decreases oral clearance of temozolomide by about 5%. The clinical implication of this effect is not known.
Caution should be exercised when Zolomide® is administered to patients with severe renal and cardiac impairment.
Store at 15o to 30oC. Protect from light.
Zolomide® cap. 100 mg: Each capsule contains Temozolomide INN 100 mg. supplied in a 5 capsule’s box.