Temozolomide
FDA Drug Information • Also known as: Temodar, Temozolomide
- Brand Names
- Temodar, Temozolomide
- Drug Class
- Alkylating Drug [EPC]
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Temozolomide is an alkylating drug. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]- as -tetrazine-8-carboxamide. The structural formula of temozolomide is: The material is a white to light tan or light pink powder with a molecular formula of C 6 H 6 N 6 O 2 and a molecular weight of 194.15. The molecule is stable at acidic pH (<5) and labile at pH >7; hence TEMODAR 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. TEMODAR capsules TEMODAR (temozolomide) capsules for oral use contains either 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg of temozolomide. The inactive ingredients are as follows: TEMODAR 5 mg: lactose anhydrous (132.8 mg), colloidal silicon dioxide (0.2 mg), sodium starch glycolate (7.5 mg), tartaric acid (1.5 mg), and stearic acid (3 mg). TEMODAR 20 mg: lactose anhydrous (182.2 mg), colloidal silicon dioxide (0.2 mg), sodium starch glycolate (11 mg), tartaric acid (2.2 mg), and stearic acid (4.4 mg). TEMODAR 100 mg: lactose anhydrous (175.7 mg), colloidal silicon dioxide (0.3 mg), sodium starch glycolate (15 mg), tartaric acid (3 mg), and stearic acid (6 mg). TEMODAR 140 mg: lactose anhydrous (246 mg), colloidal silicon dioxide (0.4 mg), sodium starch glycolate (21 mg), tartaric acid (4.2 mg), and stearic acid (8.4 mg). TEMODAR 180 mg: lactose anhydrous (316.3 mg), colloidal silicon dioxide (0.5 mg), sodium starch glycolate (27 mg), tartaric acid (5.4 mg), and stearic acid (10.8 mg). TEMODAR 250 mg: lactose anhydrous (154.3 mg), colloidal silicon dioxide (0.7 mg), sodium starch glycolate (22.5 mg), tartaric acid (9 mg), and stearic acid (13.5 mg). The body of the capsules is made of gelatin and is opaque white. The cap is also made of gelatin, and the colors vary based on the dosage strength. The...
What Is Temozolomide Used For?
1 INDICATIONS AND USAGE TEMODAR is an alkylating drug indicated for the treatment of adults with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. ( 1.1 ) Anaplastic astrocytoma. ( 1.2 ) Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma. ( 1.2 ) Treatment of adults with refractory anaplastic astrocytoma. ( 1.2 ) 1.1 Newly Diagnosed Glioblastoma TEMODAR is indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment. 1.2 Anaplastic Astrocytoma TEMODAR is indicated for the: adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; treatment of adults with refractory anaplastic astrocytoma.
Dosage and Administration
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 to 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 TEMODAR 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 TEMODAR 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. Perform complete blood counts weekly until recovery if the ANC falls below 1.5 x 10 9 /L and the platelet count falls below 100 x 10 9 /L. For concomitant use with focal radiotherapy, obtain a complete blood count weekly and as clinically indicated. 2.2 Recommended Dosage and Dosage Modifications for Newly Diagnosed Glioblastoma Administer TEMODAR either orally or intravenously once daily for 42 to 49 consecutive days during the concomitant use phase with focal radiotherapy, and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance use phase. Provide Pneumocystis pneumonia (PCP) prophylaxis during the concomitant use phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less [see Warnings and Precautions (5.3) ] . Concomitant Use Phase: The recommended dosage of TEMODAR is 75 mg/m 2 either orally or intravenously once daily for 42 to 49 days in combination with focal radiotherapy. Focal radiotherapy includes the tumor bed or resection site with a 2 to 3 cm margin. Other administration schedules have been used. Obtain a complete blood count weekly. The recommended dosage modifications due to adverse reactions during concomitant use phase are provided in Table 1 . TABLE 1: Dosage Modifications Due to Adverse Reactions During Concomitant Use Phase Adverse Reaction Interruption Discontinuation Absolute Neutrophil Count Withhold TEMODAR if ANC is greater than or equal to 0.5 × 10 9 /L and less than 1.5 × 10 9 /L....
Side Effects (Adverse Reactions)
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%) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions. ( 6.1 ) The most common Grade 3 to 4 hematologic laboratory abnormalities (≥10%) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 TEMODAR 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 TEMODAR; the most common were fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%). The most common adverse reactions (≥20%) in patients treated with TEMODAR were alopecia, fatigue, nausea, anorexia, headache, constipation, and vomiting. Table 3 summarizes the adverse reactions in MK-7365-051. TABLE 3: Adverse Reactions (≥10%) in Patients with Newly Diagnosed Glioblastoma Adverse Reactions Concomitant Use Phase Maintenance Use Phase Radiation Therapy and TEMODAR N=288 One patient who was randomized to radiation therapy-only arm received radiation therapy and TEMODAR. Radiation Therapy Alone N=285 TEMODAR N=224 All Grades (%) Grade ≥3 (%) All Grades (%) Grades ≥3 (%) All Grades (%) Grade ≥3 (%) Note: Grade 5 (fatal) adverse reactions are included in the Grade ≥3 column. Skin and Subcutaneous Tissue Alopecia 69 0 63 0 55 0 Rash 19 1 15 0 13 1 General Fatigue 54 7 49 5 61 9 Anorexia 19 1 9 <1 27 1 Headache 19 2 17 4 23 4 Gastrointestinal System Nausea 36 1 16 <1 49 1 Vomiting 20 <1 6 <1 29 2 Constipation 18 1 6 0 22 0 Diarrhea 6 0 3 0 10 1 Central and Peripheral Nervous System Convulsions 6 3 7 3 11 3 Clinically relevant adverse reactions in <10% of patients are presented below: Central & Peripheral Nervous System: memory impairment, confusion Eye: v ision blurred Gastrointestinal System: stomatitis, abdominal pain General: weakness, dizziness Immune System: allergic reaction Injury: radiation injury not otherwise specified Musculoskeletal System: arthralgia Platelet, Bleeding, & Clotting: thrombocytopenia Psychiatric: insomnia Respiratory System: coughing, dyspnea Special Senses Other: taste perversion Skin & Subcutaneous Tissue: dry skin, pruritus, erythema When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of patients, and Grade 3 or Grade 4 platelet abnormalities including thrombocytopenic reactions were observed in 14% of patients. Newly Diagnosed Anaplastic Astrocytoma The safety of TEMODAR for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma was derived from published literature [see Clinical Studies (14.2) ]. The safety of TEMODAR for the adjuvant treatment of patients with newly diagnosed anaplastic astrocytoma was consistent with the known safety profile of TEMODAR. Refractory Anaplastic Astrocytoma The safety of TEMODAR was evaluated in study MK-7365-006 [see Clinical Studies (14.2) ]. The most common adverse reactions (≥20%) were nausea, vomiting, headache, fatigue, constipation, and convulsions. Tables 4 and 5 summarize the adverse...
Contraindications
4 CONTRAINDICATIONS TEMODAR is contraindicated in patients with a history of serious hypersensitivity reactions to: temozolomide or any other ingredients in TEMODAR; and dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to TEMODAR have included anaphylaxis [see Adverse Reactions (6.2) ]. History of serious hypersensitivity to temozolomide or any other ingredients in TEMODAR and dacarbazine. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , TEMODAR 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 TEMODAR during pregnancy. These cases report similar adverse developmental outcomes to those observed in animal studies. Administration of TEMODAR 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. Data Animal Data Five consecutive days of oral administration of temozolomide at doses of 75 and 150 mg/m 2 (0.38 and 0.75 times the human dose of 200 mg/m 2 ) in rats and rabbits, respectively, during the period of organogenesis (Gestation Days 8-12) caused numerous malformations of the external and internal organs and skeleton in both species. In rabbits, temozolomide at the 150 mg/m 2 dose (0.75 times the human dose of 200 mg/m 2 ) caused embryolethality as indicated by increased resorptions.
Overdosage
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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING TEMODAR is a hazardous drug. Follow applicable special handling and disposal procedures. 1 TEMODAR capsules TEMODAR capsules are supplied in child-resistant sachets containing the following capsule strengths: 5 mg: opaque white bodies with green caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-3004-03 14-count – NDC 0085-3004-04 20 mg: opaque white bodies with yellow caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-1519-03 14-count – NDC 0085-1519-04 100 mg: opaque white bodies with pink caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-1366-03 14-count – NDC 0085-1366-04 140 mg: opaque white bodies with blue caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-1425-03 14-count – NDC 0085-1425-04 180 mg: opaque white bodies with orange caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-1430-03 14-count – NDC 0085-1430-04 250 mg: opaque white bodies with white caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with “TEMODAR”. They are supplied as follows: 5-count – NDC 0085-1417-02 Store TEMODAR Capsules at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. TEMODAR for injection TEMODAR for injection is supplied in...
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.