Temozolomide

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.

• 1. INDICATIONS AND USAGE TEMOZOLOMIDE Capsules are an alkylating drug indicated for the treatment of adult patients with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.

• 4. CONTRAINDICATIONS TEMOZOLOMIDE is contraindicated in patients with a history of hypersensitivity reactions to: • temozolomide or any other ingredients in TEMOZOLOMIDE; and • dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide.contraindicated

2. DOSAGE AND ADMINISTRATION Administer either orally or intravenously. (2.4) Newly Diagnosed Glioblastoma: 75 mg/m 2 once daily for 42 to 49 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m 2 once daily for Days 1 to 5 of each 28-day cycle for 6 cycles. May increase maintenance dose to 200 mg/ m 2 for cycles 2 – 6 based on toxicity. ( 2.1 ) Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to grade 1 or less. ( 2.1 ) Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma: Beginning 4 weeks after the end of radiotherapy, administer TEMOZOLOMIDE Capsules orally in a single dose on days 1-5 of a 28-day cycle for 12 cycles. The recommended dosage for Cycle 1 is 150 mg/m 2 per day and for Cycles 2 to 12 is 200 mg/m 2 if patient experienced no or minimal toxicity in Cycle 1. ( 2.2 ) Refractory Anaplastic Astrocytoma : Initial dose of 150 mg/m 2 once daily on Days 1 to 5 of each 28-day cycle. ( 2.2 ) 2.1 Monitoring to Inform Dosage and Administration Prior to dosing, withhold TEMOZOLOMIDE until patients have an absolute neutrophil count (ANC) of 1.5 x 10 9 /L or greater and a platelet count of 100 x 10 9 /L or greater. For concomitant radiotherapy, obtain a complete blood count prior to initiation of treatment and weekly during treatment. For the 28-day treatment cycles, obtain a complete blood count prior to treatment on Day 1 and on Day 22 of each cycle.

5. WARNINGS AND PRECAUTIONS Myelosuppression: Monitor absolute neutrophil count (ANC) and platelet count prior to each cycle and during treatment. Geriatric patients and women have a higher risk of developing myelosuppression. ( 5.1 , 8.5 ) Hepatotoxicity : Fatal and severe hepatotoxicity have been reported. Perform liver tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately 2 to 4 weeks after the last dose of TEMOZOLOMIDE ( 5.2 ) Pneumocystis Pneumonia (PCP): Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP.( 5.3 ) Secondary Malignancies : Myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed. ( 5.4 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. Advise male patients with pregnant partners or female partners of reproductive potential to use condoms. ( 5.5 , 8.1 , 8.3 ) Exposure to Opened Capsules : TEMOZOLOMIDE capsules should not be opened, chewed, or dissolved but should be swallowed whole with a glass of water. ( 5.6 ) 5.1 Myelosuppression Myelosuppression, including pancytopenia, leukopenia and anemia, some with fatal outcomes, have occurred with TEMOZOLOMIDE [see Adverse Reactions ( 6.1 , 6.2 )] . In MK-7365-006, myelosuppression usually occurred during the first few cycles of therapy and was generally not cumulative.

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions ( 5.1 )]. Hepatotoxicity [see Warnings and Precautions ( 5.2 )]. Pneumocystis Pneumonia [see Warnings and Precautions ( 5.3 )]. Secondary Malignancies [see Warnings and Precautions ( 5.4 )]. The most common adverse reactions (≥ 20% incidence) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions. ( 6.1 ) The most common Grade 3 to 4 hematologic laboratory abnormalities (≥ 10% incidence) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Devatis Inc. at 1-833-534-4406 or druginfo@devatis.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch or www.devatis.com. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Newly Diagnosed Glioblastoma The safety of TEMOZOLOMIDE was evaluated in Study MK-7365-051 [see Clinical Studies ( 14.1 )]. Severe or life-threatening adverse reactions occurred in 49% of patients treated with TEMOZOLOMIDE; the most common were fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%).

8. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] TEMOZOLOMIDE can cause fetal harm when administered to a pregnant woman. Available postmarketing reports describe cases of spontaneous abortions and congenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies with exposure to TEMOZOLOMIDE during pregnancy. These cases report similar adverse developmental outcomes to those observed in animal studies. Administration of TEMOZOLOMIDE to rats and rabbits during the period of organogenesis caused numerous external, internal, and skeletal malformations at doses less than the maximum human dose based on body surface area (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Following a single oral dose of 150 mg/m 2 , the mean C max is 7.5 mcg/mL for temozolomide and 282 ng/mL for MTIC. The mean AUC is 23.4 mcg·hr/mL for temozolomide and 864 ng·hr/mL for MTIC.

10. OVERDOSAGE Dose-limiting toxicity was myelosuppression and was reported with any dose but is expected to be more severe at higher doses. An overdose of 2000 mg per day for 5 days was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi-organ failure, and death. There are reports of patients who have taken more than 5 days of treatment (up to 64 days), with adverse reactions reported including myelosuppression, which in some cases was severe and prolonged, and infections and resulted in death. In the event of an overdose, monitor complete blood count and provide supportive measures as necessary.

• Aug 11, 1999NDANDA021029Merck Sharp Dohme
• Feb 27, 2009NDANDA022277Merck Sharp Dohme
• Feb 12, 2014ANDAANDA201742Sun Pharm
• May 8, 2015ANDAANDA203691Amneal Pharms
• Apr 27, 2016ANDAANDA206309Rising
• Feb 27, 2017ANDAANDA201528Accord Hlthcare
• Apr 26, 2017ANDAANDA207658Deva Holding As
• Nov 23, 2021ANDAANDA213328Nivagen Pharms Inc

1. 1Disease Progression1,8749.1%
2. 2Off Label Use1,7368.4%
3. 3Death1,7308.4%
4. 4Thrombocytopenia1,5577.5%
5. 5Product Use In Unapproved Indication1,4266.9%
6. 6Nausea1,2976.3%
7. 7Drug Ineffective1,2506.1%
8. 8Neutropenia1,0265.0%
9. 9Fatigue1,0255.0%
10. 10Vomiting9724.7%
11. 11Malignant Neoplasm Progression9104.4%
12. 12Febrile Neutropenia8214.0%
13. 13Diarrhoea7773.8%
14. 14Anaemia7553.7%
15. 15Asthenia6393.1%

Recent PubMed references pinned to Temozolomide as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Hsa-miR-25-3p Inhibition Sensitizes Patient-Derived Glioblastoma Cells to Temozolomide via β-catenin Downregulation.
  Cellular and molecular neurobiology · 2026 · Richter K, Markmann H, Kaps P, et al.
  PMID 42218313DOI 10.1007/s10571-026-01750-6
• Implications of the Cuproptosis Protein SLC31A1 for the Immune Microenvironment and Temozolomide Sensitivity in Glioblastoma.
  Anticancer research · 2026 · Xu D, DU G, Sun J, et al.
  PMID 42203322DOI 10.21873/anticanres.18188
• Real-World Effectiveness of Capecitabine and Temozolomide Across Endocrine and Neuroendocrine Neoplasm Subtypes (ENENs): A Population-Based Cohort Study from Alberta, Canada (2011-2021).
  Current oncology (Toronto, Ont.) · 2026 · Aleksi A, Jobin KD, Hannouf MB, et al.
  PMID 42187606DOI 10.3390/curroncol33050289
• Stress granule assembly represents a therapeutic vulnerability in super-enhancer-driven circMLB-mediated glioblastoma temozolomide resistance.
  Cancer letters · 2026 · Huang R, Yang Z, Dong Y, et al.
  PMID 42167397DOI 10.1016/j.canlet.2026.218601
• [(177)Lu]Lu-DOTATATE PRRT and CAPTEM chemotherapy for pancreas and small bowel neuroendocrine tumours: The AGITG CONTROL NETS Multi-centre randomized trial.
  European journal of cancer (Oxford, England : 1990) · 2026 · Chan DL, Sjoquist KM, Ransom DT, et al.
  PMID 42142431DOI 10.1016/j.ejca.2026.116781
• Prolonged sequential temozolomide in glioblastoma: A systematic review with exploratory quantitative synthesis.
  Cancer treatment and research communications · 2026 · Pasqualetti F, Ius T, Montemurro N, et al.
  PMID 42114299DOI 10.1016/j.ctarc.2026.101231
• Temozolomide reconsidered: Real-World evidence in resistant melanoma cases.
  The oncologist · 2026 · Maselli-Schoueri JH, Martinez E, Lagos E, et al.
  PMID 42105220DOI 10.1093/oncolo/oyag184
• Levetiracetam reverses temozolomide resistance in glioblastoma by blocking drug efflux through RAB5A/CD63-RAB35 axis.
  Cancer letters · 2026 · Zhao J, Li M, Zhang Q, et al.
  PMID 42097495DOI 10.1016/j.canlet.2026.218577

The 10 most recently updated of 1,222 ClinicalTrials.gov registrations naming Temozolomide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of Olutasidenib and Temozolomide in HGG
  Recruiting · Phase 2 · Interventional · 60 enrolled · Rigel Pharmaceuticals
  NCT06161974updated 2026-06-12
• A Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 116 enrolled · Debiopharm International SA
  NCT05765812updated 2026-06-12
• Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
  Recruiting · Phase 3 · Interventional · 478 enrolled · National Cancer Institute (NCI)
  NCT06172296updated 2026-06-12
• A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
  Recruiting · Phase 2 · Phase 3 · Interventional · 2,250 enrolled · Global Coalition for Adaptive Research
  NCT03970447updated 2026-06-12
• Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness
  Recruiting · Phase 1 · Phase 2 · Interventional · 42 enrolled · National Cancer Institute (NCI)
  NCT05691491updated 2026-06-11
• Natural Killer Cell Therapy (UD TGFbetai NK Cells) and Temozolomide for the Treatment of Stage IV Melanoma Metastatic to the Brain
  Recruiting · Phase 1 · Phase 2 · Interventional · 24 enrolled · Kari Kendra
  NCT05588453updated 2026-06-11
• Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII
  Recruiting · Phase 2 · Interventional · 162 enrolled · Black Diamond Therapeutics, Inc.
  NCT07326566updated 2026-06-11
• Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 447 enrolled · National Cancer Institute (NCI)
  NCT02152982updated 2026-06-11
• New Adjuvant Vaccine in Glioblastoma, a Phase 1/2a Study
  Recruiting · Phase 1 · Phase 2 · Interventional · 35 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT06622434updated 2026-06-11
• NANT 2021-01 Phase II STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial
  Recruiting · Phase 2 · Interventional · 62 enrolled · New Approaches to Neuroblastoma Therapy Consortium
  NCT06450041updated 2026-06-10

Frequently asked questions

How does Temozolomide work?

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.

What is Temozolomide used for?

According to FDA labeling, Temozolomide carries indications including: 1. INDICATIONS AND USAGE TEMOZOLOMIDE Capsules are an alkylating drug indicated for the treatment of adult patients with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Temozolomide?

Temozolomide is classified as Other alkylating agents, Alkylating Drug, Alkylating Activity, Decreased DNA Integrity, Decreased DNA Replication.

What are the brand names for Temozolomide?

Temozolomide is marketed under brand names including Temodar.

What are the contraindications for Temozolomide?

Temozolomide labeling lists contraindications including: 4. CONTRAINDICATIONS TEMOZOLOMIDE is contraindicated in patients with a history of hypersensitivity reactions to: • temozolomide or any other ingredients in TEMOZOLOMIDE; and • dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide.. Always consult the full prescribing information and a clinician.