Temozolomide

194.15

194.15

1308068-626-2

YF1K15M17Y

759883|362856

DTXSID5043714

C1244

L01AX03|L - Antineoplastic and immunomodulating agents

2933990090

106

-1.1

white to light brown

2.0±0.1 g/cm3

212 °C (decomp)

526.6°C at 760 mmHg

272.3±27.9 °C

1.895

DMSO: soluble 10mg/mL, clear

2-8°C

NONH for all modes of transport

3

45-46-60-61-22-36/37/38

24/25-45-36/37-26-53-36

NJ5927050

T,Xi

P201-P261-P305 + P351 + P338-P308 + P313

H302-H315-H319-H335-H350-H360

|Danger|H300 (52.1%): Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P310, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 167 companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Serum aminotransferase elevations occur during temozolomide therapy in up to 12% of patients, but these elevations are usually mild and self-limited, not requiring dose adjustment or drug discontinuation. An instance of serum aminotransferase elevation with jaundice was reported in the registration trials of temozolomide and subsequent to its approval. More strikingly, multiple single case reports and several case series of temozolomide hepatotoxicity have been reported in the literature. The onset of injury was typically within 2 to 8 weeks of starting temozolomide but several patients had received multiple courses before the onset of liver injury. The pattern of serum enzyme elevations was usually mixed initially, but the disease tended to be cholestatic. In several instances, jaundice was deep and prolonged. Features of hypersensitivity (rash, fever, eosinophilia) and autoantibody formation were not present. Liver histology demonstrated cholestasis and bile duct injury and a striking decrease in bile ducts (bile duct loss or paucity). Jaundice and pruritus tended to be prolonged and some patients developed vanishing bile duct syndrome, while others recovered clinically but had persistent serum alkaline phosphatase elevations during follow up and to the time of death from the brain tumor. Rechallenge was not done, but several patients subsequently received other antineoplastic agents, some of which were alkylating agents without recurrence of liver injury.

15%

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.|FDA Label|For the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy (RT) and subsequently as monotherapy treatment.For the treatment of children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.|Temodal hard capsules is indicated for the treatment of:adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment;children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.|Temomedac hard capsules is indicated for the treatment of:adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy (RT) and subsequently as monotherapy treatment;children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.|Temozolomide Sun is indicated for the treatment of:adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy (RT) and subsequently as monotherapy treatment;children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.|Treatment of malignant glioma|Drug: Temozolomide

Temozolomide is an orally administered alkylating agent used largely in the therapy of malignant brain tumors including glioblastoma and astrocytoma. Temozolomide has been associated with a low rate of serum enzyme elevations during treatment and with rare instances of clinically apparent cholestatic liver injury.

Antineoplastic Agents, Alkylating Agents

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.

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)

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.|0.4 L/kg|5.5 L/hr/m2

Approximately 1.8 hours.

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.

8-carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one

Human drugs -> Temozolomide Teva -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Temozolomide Accord -> EMA Drug Category|Human drugs -> Temodal -> EMA Drug Category|Human drugs -> Temomedac -> EMA Drug Category|Human drugs -> Temozolomide Hexal -> EMA Drug Category|Human drugs -> Temozolomide Sun -> EMA Drug Category|Human drugs -> Temozolomide Sandoz -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients