Temozolomide hospira 5, 20, 100, 140, 180 and 250 mg hard capsules is a generic medicinal product containing temozolomide as active substance. Stevens, in cancer drug design and discovery second edition, 2014 summary. Great care should be taken to prevent inhaling particles of temozolomide and. The active substance of the reference product is temozolomide. Chemical hazard, click to download safety data sheet. Temozolomide is an imidazotetrazine that is 3,4dihydroimidazo5,1d1,2,3,5tetrazine which is substituted at positions 3, 4, and 8 by methyl, oxo, and carboxamide groups, respectively. The majority of patients received temodal, once daily for five days, repeating every 28 days up to the high dose of 200 mgm2day. Temozolomide is a triazene analog of dacarbazine with antineoplastic activity. You must avoid getting pregnant or fathering a child while you are on temozolomide. Information for the user temozolomide 5 mg hard capsules temozolomide 20 mg hard capsules. Temozolomide d3 safety data sheet according to regulation ec no.
The cytotoxicity of mtic is thought to be due primarily to methylation of dna at the o. In vivo it spontaneously degrades and reacts with water to release a methyldiazonium cation which preferentially methylates dna at n7 positions of guanine in guanine rich regions. A process for the preparation of compounds of formula ia, where rch 3 i. Interaction of temozolomide with dna and repair processes. Temozolomide is rapidly and completely absorbed after oral administration. Page 1 temozolomide oral chemotherapy education name of your medication generic name temozolomide teh moh zoh loh mide brand name temodar teh moh dar approved uses temozolomide is used to treat anaplastic astrocytoma and glioblastoma multiforme. For research use only, not for human or veterinary use. Following a single oral dose of 150 mgm 2, temozolomide and its active mtic metabolite had c max values of 7. The most common side effects with temozolomide are nausea feeling sick, vomiting, constipation, loss of appetite, alopecia hair loss, headache, fatigue tiredness. Food reduces the rate and extent of temozolomide absorption. Temozolomide, a new drug, has shown promise in treating malignant gliomas and other difficulttotreat tumors. Temozolomide induces g2m arrest and apoptosis through adduction of a methyl group to o6 position of guanine in genomic dna and functional inactivation of dna repair protein o6alkylguanine dna alkyltransferase agt in base excision. Temozolomide is a second generation imidazotetrazine anticancer chemotherapeutic that is clinically approved to treat gliobastoma multiforme, anaplastic astrocytoma, and oligodendrocytoma.
Due to the high sensitivity of temozolomide to basic ph values the recoveryincluding process is especially advantageous because it enables obtaining high yields of highly. Therefore, temozolomide may be administered both orally and intravenously with a median t max of one hour. Extensive subdural spread of a glioblastoma associated with subdural hygroma. Orion temozolomide 20 mg capsules have a white opaque capsule with two stripes in orange. Identification of the substancemixture and of the companyundertaking product name. Temozolomide tmz is the first new chemotherapy agent to be approved for the treatment of high. New zealand datasheet 1 product name orion temozolomide capsules. Temozolomide temodar is an oral alkylating agent approved by the fda for use in the firstline treatment of glioblastoma multiforme as well as for recurrent anaplastic astrocytoma. Temozolomide dosing should be interrupted or discontinued during concomitant phase according to the hematological and nonhematological toxicity criteria as noted in. We have a range of complex generics and drug delivery based formulations. Getwell oncology in india is a manufacturer and supplier of temozolomide capsules temzol at a cost effective price.
Temozolomide tmz is a methylating agent of the imidotetrazine class, whose cytotoxic product is o 6methylguanine dna adducts, which initiate a futile recycling of the mismatch repair pathway causing dna strand breaks and apoptotic cell death in mismatch repair proficient cells. Temodar is indicated for the treatment of adult patients with refractory anaplastic astrocytoma, i. Reconstituted temodaris a clear solutionand essentially free of visible particles. Temozolomide acts as an alkylating agent, attaching alkyl groups to guanine bases in dna and interfering with dna replication.
Temozolomide is an highly orallyavailable, imidazotetrazinebased, monofunctional dna alkylating agent. Additional offlabel nccn compendial uses for temozolomide, meeting nccn categories 1. Temozolomide stability in extemporaneously compounded oral. Both temozolomide and dacarbazine are prodrugs of mtic. Temozolomide, a novel alkylating agent with activity in the. Us8258294b2 process for the preparation of temozolomide. Temozolomide is a dna methylating agent and drug resistancemodifying agent. In the case of liquids, use proper absorbent materials. Stevens, in cancer drug design and discovery second edition, 2014. Material safety data sheet of temozolomide tmz abmole.
Dec 14, 2020 temozolomide is spontaneously hydrolyzed at physiologic ph to the active species, mtic and to temozolomide acid metabolite. Discard if particulate matter or discoloration is observed. This novel oral alkylating agent has demonstrated promising activity not only in brain tumors, but in a variety of solid tumors, including malignant melanoma. Temozolomide stability in extemporaneously compounded. Additional offlabel nccn compendial uses for temozolomide, meeting nccn categories 1, 2a or 2b, are approved for the following indications. Mtic is further hydrolyzed to 5aminoimidazole4carboxamide aic, which is known to be an intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species. Guidance on the compilation of safety data sheets echa europa. The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of temozolomide in two extempora. Temzol temozolomide capsules manufacturer in india. Tmz has certain advantages over many existing alkylating agents because. The present invention provides a process for preparing highly pure temozolomide base which includes recovery from the purification mother liquors by using an anionic exchange resin.
Jul 31, 2020 temozolomide for injection definition temozolomide for injection is a sterile, lyophilized mixture of temozolomide and suitable added substances. Temozolomide induces g2m arrest and apoptosis through adduction of a methyl group to o6 position of guanine in genomic dna and functional inactivation of dna repair protein o6alkylguanine dna alkyltransferase agt in base excision repair ber pathway. Buy highly pure temozolomide related compound a 4diazo4himidazole5carboxamide 1643554, cas no. Temozolomide is indicated in adult patients for the treatment of newly diagnosed.
Temozolomide is a prodrug that acts as a molecular delivery device to transport a reactive methylating species to guaninerich sequences in the major groove of dna. Temozolomide 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg capsules. Kenilworth, nj is a novel oral alkylating agent that has demonstrated efficacy in the treatment of a variety of solid tumors, including primary malignant brain tumors and metastatic melanoma 1. Temozolomide tmz, sold under the brand name temodar among others, is a medication used to treat some brain tumors such as glioblastoma multiforme or anaplastic astrocytoma.
The reference medicinal product temodal 5, 20, 100, 140, 180, 250 mg hard capsules, has been centrally authorized on 26 january 1999. Mtic is further hydrolyzed to 5aminoimidazole4carboxamide aic, which is known to be an intermediate in purine and nucleic acid biosynthesis and to methylhydrazine, which is believed to be the active alkylating species. A prodrug for mtic 53methyltriaz1en1yl1himidazole4carboxamide, formed by spontaneous hydrolysis of temozolomide in the body, it is used as an oral alkylating agent for the treatment of newly. Temzol temozolomide capsules manufacturer in india getwell. Sigmaaldrich offers a number of temozolomide products. Harmful by inhalation, in contact with skin and if swallowed. No chemical in this material are subject to the reporting requirements of sara title iii, section 302. Mar 11, 2020 o store temozolomide at room temperature 68f77f in a dry location away from light. Temozolomide 3,4dihydro3methyl 85622931 c 6 h 6 n 6 0 2. Temozolomide tzm, as a single agent, does not significantly increase mdian survival time mst with respect to control. By treating temozolomide hydrochloride with a mixture of an organic acid, a water miscible organic solvent, and water, temozolomide free base is obtained in an acidic medium.
Temozolomide is rapidly and completely absorbed in the gastrointestinal tract and is stable at both acidic and neutral ph. A 12hour regimen has been tested, and clinical trials involving 4. Temozolomide stability in extemporaneously compounded oral suspensions abstract temozolomide, commercially available in capsules, is an oral alkylating agent used to treat brain tumors. Temozolomide is spontaneously hydrolyzed at physiologic ph to the active species, mtic and to temozolomide acid metabolite. Ccrg 81045 is an oral dna alkylating agent used to treat some brain cancers. Features and benefits this compound is a featured product for apoptosis research. Sds of temozolomide, safety data sheets, cas 85622931. Temodar temodal in the united kingdom and europe, schering. Mar 23, 2020 temozolomide may reduce certain kinds of blood cells which are important for blood clotting and fighting infections. In advance of clinical experience, learner will download and. This material does not contain any chemical components with known cas numbers that exceed the. Pulsed and discontinuous electromagnetic field exposure decreases temozolomide resistance in glioblastoma by modulating the expression of o6methylguaninedna methyltransferase, cyclind1, and p53. Temozolomide has been well characterised and possesses an acceptable clinical safety profile as demonstrated in 1017 patients with malignant glioma, melanoma, or other advanced cancers.
Temozolomide promiscuously methylates a range of sites in purine residues of dna, notably at the n 7 position of guanine. Visually inspect reconstituted solutionfor particulatematter and discoloration. Noteworthy, intracranial injection of nu1025, immediately before the administration of 100 or 200 mgkg temozolomide, significantly increases lifespans with respect to controls or to groups treated with temozolomide only. Temozolomide dosage modifications during maintenance treatment toxicity interruption and dose reduction discontinuation absolute neutrophil count withhold temozolomide if anc less than 1. The dna repair protein o 6alkylguanine dna alkyltransferase agt repairs these adducts in a suicide manner and. Temozolomide plasma protein binding varies from 836%, with an average of around 15%. Temozolomide is an oral prodrug that is hydrolyzed in vivo to the alkylating antineoplastic agent 53methyltriazen1ylimidazole4carboxamide. Temozolomide undergoes rapid chemical conversion at physiologic ph to the active compound, monomethyl triazeno imidazole carboxamide mtic. Temozolomide dna alkylating agent cellagen technology.
Temozolomide is an imidazotetrazine prodrug that is stable at acidic ph but undergoes. Temozolomide tzm is a methylating agent that crosses the bloodbrain barrier and is indicated for malignant gliomas and metastatic mel. Accidental release measures contain spill and collect, as appropriate. Temozolomide, targets, molecular targets, and validated targets. Temozolomide temodar american journal of neuroradiology.
266 337 421 226 1768 1263 533 981 577 666 1678 1739 1460 68 1386 615 327 1587 733 710 1506 714 619 1638 1734 626 364 499 59 1600 1666 1309 1625 364 699 952 133 688