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TEMODAR is a brand name for Temozolomide. The medicine, its uses, side effects and dosage are the same regardless of brand.
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 )…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Administer either orally or intravenously. 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. 1 ) Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less.
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 ) Refractory Anaplastic Astrocytoma: Initial dose of 150 mg/m 2 once daily on Days 1 to 5 of each 28-day cycle. 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 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 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.
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 . 5 × 10 9 /L. 5 × 10 9 /L. 5 × 10 9 /L. Platelet Count Withhold TEMODAR if platelet count is greater than or equal to 10 × 10 9 /L and less than 100 × 10 9 /L.
4) ] The most common adverse reactions (≥20%) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions. 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.
gov/medwatch . 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.
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.
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 ) 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 TEMODAR. 2 ) Pneumocystis Pneumonia (PCP) : Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP.
3 ) Secondary Malignancies: Myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed. 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. 3 ) Exposure to Opened Capsules: TEMODAR capsules should not be opened, chewed, or dissolved but should be swallowed whole with a glass of water.
2) ] . In MK-7365-006, myelosuppression usually occurred during the first few cycles of therapy and was generally not cumulative. The median nadirs occurred at 26 days for platelets (range: 21 to 40 days) and 28 days for neutrophils (range: 1 to 44 days).
Approximately 10% of patients required hospitalization, blood transfusion, or discontinuation of therapy due to myelosuppression. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression.
Obtain a complete blood count and monitor ANC and platelet counts before initiation of treatment and as clinically indicated during treatment. 3) ]. 3) ] . 2 Hepatotoxicity Fatal and severe hepatotoxicity have been reported in patients receiving TEMODAR.
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.
2) ]. History of serious hypersensitivity to temozolomide or any other ingredients in TEMODAR and dacarbazine. ( 4 )
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Discontinue TEMODAR if platelet count is less than 10 × 10 9 /L. Resume TEMODAR at the same dose when platelet count is greater than or equal to 100 × 10 9 /L. Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting) Withhold TEMODAR if Grade 2 adverse reaction occurs.
Discontinue TEMODAR if Grade 3 or 4 adverse reaction occurs. Resume TEMODAR at the same dose when resolution to Grade 1 or less.
Single Agent Maintenance Use Phase:
Beginning 4 weeks after concomitant use phase completion, administer TEMODAR either orally or intravenously once daily on Days 1 to 5 of each 28-day cycle for 6 cycles.
The recommended dosage of TEMODAR in the maintenance use phase is:
Cycle 1: 150 mg/m 2 per day on days 1 to 5.
Cycles 2 to 6:
May increase to 200 mg/m 2 per day on days 1 to 5 before starting Cycle 2 if no dosage interruptions or discontinuations are required (Table 1). If the dose is not escalated at the onset of Cycle 2, do not increase the dose for Cycles 3 to 6.
5 × 10 9 /L and the platelet count is above 100 × 10 9 /L. Do not start the next cycle until the ANC and platelet count exceed these levels. The recommended dosage modifications due to adverse reactions during the maintenance use phase are provided in Table 2 .
If TEMODAR is withheld, reduce the dose for the next cycle by 50 mg/m 2 per day. Permanently discontinue TEMODAR in patients who are unable to tolerate a dose of 100 mg/m 2 per day.
TABLE 2:
Dosage Modifications Due to Adverse Reactions During Maintenance and Adjuvant Treatment Adverse Reactions Interruption and Dose Reduction Discontinuation Absolute Neutrophil Count Withhold TEMODAR if ANC less than 1 × 10 9 /L. Discontinue TEMODAR if unable to tolerate a dose of 100 mg/m 2 per day.
5 × 10 9 /L, resume TEMODAR at reduced dose for the next cycle. Platelet Count Withhold TEMODAR if platelet less than 50 × 10 9 /L. Discontinue TEMODAR if unable to tolerate a dose of 100 mg/m 2 per day. When platelet count is above 100 × 10 9 /L, resume TEMODAR at reduced dose for the next cycle.
Nonhematological Adverse Reactions (except for alopecia, nausea, vomiting) Withhold TEMODAR if Grade 3 adverse reaction occurs. Discontinue TEMODAR if recurrent Grade 3 adverse reaction occurs after dose reduction, if Grade 4 adverse reaction occurs, or if unable to tolerate a dose of 100 mg/m 2 per day.
When resolved to Grade 1 or less, resume TEMODAR at reduced dose for the next cycle. 3 Recommended Dosage and Dosage Modifications for Anaplastic Astrocytoma 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 to 5 of a 28-day cycle for 12 cycles.
The recommended dosage of TEMODAR is:
Cycle 1: 150 mg/m 2 per day on days 1 to 5. Cycles 2 to 12: 200 mg/m 2 per day on days 1 to 5 if patient experienced no or minimal toxicity in Cycle 1. If the dose was not escalated at the onset of Cycle 2, do not increase the dose during Cycles 3 to 6.
2) ] . Refractory Anaplastic Astrocytoma The recommended initial dosage of TEMODAR is 150 mg/m 2 once daily on Days 1 to 5 of each 28-day cycle. 5 × 10 9 /L, and Platelet count is greater than or equal to 100 × 10 9 /L. Continue TEMODAR until disease progression or unacceptable toxicity.
5 x 10 9 /L and the platelet count is above 100 x 10 9 /L. Do not start the next cycle until the ANC and platelet count exceed these levels. If the ANC is less than 1 × 10 9 /L or the platelet count is less than 50 × 10 9 /L during any cycle, reduce the TEMODAR dose for the next cycle by 50 mg/m 2 per day.
Permanently discontinue TEMODAR in patients who are unable to tolerate a dose of 100 mg/m 2 per day. 4 Preparation and Administration TEMODAR is a hazardous drug. Follow applicable special handling and disposal procedures. 1 TEMODAR capsules Take TEMODAR at the same time each day.
Administer TEMODAR consistently with respect to food (fasting vs. 3) ] . To reduce nausea and vomiting, take TEMODAR on an empty stomach or at bedtime and consider antiemetic therapy prior to and following TEMODAR administration. Swallow TEMODAR capsules whole with water.
6) ] . If capsules are accidentally opened or damaged, take precautions to avoid inhalation or contact with the skin or mucous membranes . In case of powder contact, wash the affected area with water immediately. TEMODAR for injection Bring the vial to room temperature prior to reconstitution with Sterile Water for Injection.
5 mg/mL temozolomide. Reconstituted TEMODAR is a clear solution and essentially free of visible particles. Gently swirl vial. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Discard if particulate matter or discoloration is observed. Do not further dilute the reconstituted solution. Store reconstituted solution at room temperature (25°C [77°F]). Discard reconstituted solution if not used within 14 hours, including infusion time.
Withdraw up to 40 mL from each vial to make up the total dose and discard any unused portion. Transfer reconstituted solution from each vial into an empty 250 mL infusion bag. Administer reconstituted solution using a pump over a period of 90 minutes.
Administer TEMODAR by intravenous infusion only. Infusion over a shorter or longer period of time may result in suboptimal dosing. Flush the lines before and after each infusion. 9% Sodium Chloride injection only. Because no data are available on the compatibility of TEMODAR for injection with other intravenous substances or additives, do not infuse other medications simultaneously through the same intravenous line.
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. 2) ]. The most common adverse reactions (≥20%) were nausea, vomiting, headache, fatigue, constipation, and convulsions.
Tables 4 and 5 summarize the adverse reactions and hematological laboratory abnormalities in MK-7365-006.
TABLE 4:
Adverse Reactions (≥10%) in Patients with Refractory Anaplastic Astrocytoma Adverse Reactions TEMODAR N=158 All Reactions (%) Grades 3-4 (%) Gastrointestinal System Nausea 53 10 Vomiting 42 6 Constipation 33 1 Diarrhea 16 2 General Headache 41 6 Fatigue 34 4 Asthenia 13 6 Fever 13 2 Central and Peripheral Nervous System Convulsions 23 5 Hemiparesis 18 6 Dizziness 12 1 Coordination abnormal 11 1 Amnesia 10 4 Insomnia 10 0 Cardiovascular Edema peripheral 11 1 Resistance Mechanism Infection viral 11 0 Clinically relevant adverse reactions in <10% of patients are presented below: Central and Peripheral Nervous System: paresthesia, somnolence, paresis, urinary incontinence, ataxia, dysphasia, convulsions local, gait abnormal, confusion Endocrine: adrenal hypercorticism Gastrointestinal System: abdominal pain, anorexia General: back pain Metabolic: weight increase Musculoskeletal System: myalgia Psychiatric : anxiety, depression Reproductive Disorders: breast pain female Respiratory System: upper respiratory tract infection, pharyngitis, sinusitis, coughing Skin & Appendages: rash, pruritus Urinary System: urinary tract infection, micturition increased frequency Vision: diplopia, vision abnormal This term includes blurred vision; visual deficit; vision changes; and vision troubles.
TABLE 5:
Grade 3 to 4 Hematologic Laboratory Abnormalities That Worsened from Baseline in Patients with Refractory Anaplastic Astrocytoma TEMODAR Change from Grade 0 to 2 at baseline to Grade 3 or 4 during treatment. 5 × 10 9 /L) and thrombocytopenia (<20 × 10 9 /L) than males in the first cycle of therapy (12% vs.
5% and 9% vs. 3%, respectively). In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 10% (6/63) of patients >70 years experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
For patients ≤70 years, 7% (62/871) and 6% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. Pancytopenia, leukopenia, and anemia also occurred. Injection Site Reactions Adverse reactions that were reported in 35 patients who received TEMODAR for injection were pain, irritation, pruritus, warmth, swelling, and erythema at infusion site; petechiae; and hematoma.
2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of TEMODAR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.
Dermatologic :
Toxic epidermal necrolysis and Stevens-Johnson syndrome.
Immune System :
Hypersensitivity reactions, including anaphylaxis. Erythema multiforme, which resolved after discontinuation of TEMODAR and, in some cases, recurred upon rechallenge.
Hematopoietic :
Prolonged pancytopenia, which may result in aplastic anemia and fatal outcomes.
Hepatobiliary :
Fatal and severe hepatotoxicity, elevation of liver enzymes, hyperbilirubinemia, cholestasis, and hepatitis.
Infections :
Serious opportunistic infections, including some cases with fatal outcomes, with bacterial, viral (primary and reactivated), fungal, and protozoan organisms.
Pulmonary :
Interstitial pneumonitis, pneumonitis, alveolitis, and pulmonary fibrosis.
Endocrine :
Diabetes insipidus.
Perform liver tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately two to four weeks after the last dose of TEMODAR. 3 Pneumocystis Pneumonia Pneumocystis pneumonia (PCP) has been reported in patients receiving TEMODAR.
The risk of PCP is increased in patients receiving steroids or with longer treatment regimens of TEMODAR. For patients with newly diagnosed glioblastoma, provide PCP prophylaxis for all patients during the concomitant phase. 1) ] . Monitor all patients receiving TEMODAR for the development of lymphopenia and PCP.
4 Secondary Malignancies The incidence of secondary malignancies is increased in patients treated with TEMODAR-containing regimens. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed following TEMODAR administration.
5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TEMODAR can cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been reported in both pregnant patients and pregnant partners of male patients.
Oral administration of temozolomide to rats and rabbits during the period of organogenesis resulted in embryolethality and polymalformations at doses less than the maximum human dose based on body surface area. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with TEMODAR and for 6 months after the last dose. Because of potential risk of genotoxic effects on sperm, advise male patients with female partners of reproductive potential to use condoms during treatment with TEMODAR and for 3 months after the last dose.
3) ]. 6 Exposure to Opened Capsules Advise patients not to open, chew or dissolve the contents of the TEMODAR capsules. Swallow capsules whole with a glass of water. If a capsule becomes damaged, avoid contact of the powder contents with skin or mucous membranes.
4) ] . If TEMODAR capsules must be opened or the contents must be dissolved, this should be done by a professional trained in safe handling of hazardous drugs using appropriate equipment and safety procedures.