Advertisement

Topics

These highlights do not include all the information needed to use TEMODAR safely and effectively. See full prescribing information for TEMODAR. TEMODAR (temozolomide) CapsulesTEMODAR (temozolomide) for Injection administered via intravenous infusion | TEMODAR

05:26 EDT 27th August 2014 | BioPortfolio

Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

TEMODAR® (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

TEMODAR is indicated for the treatment of adult patients with refractory anaplastic astrocytoma, i.e., patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

The recommended dose for TEMODAR as an intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes [see Clinical Pharmacology (12.3)]. Dosage of TEMODAR must be adjusted according to nadir neutrophil and platelet counts in the previous cycle and the neutrophil and platelet counts at the time of initiating the next cycle. For TEMODAR dosage calculations based on body surface area (BSA) see Table 5 . For suggested capsule combinations on a daily dose see Table 6 .

Patients with Newly Diagnosed High Grade Glioma:

Concomitant Phase:

TEMODAR is administered at 75 mg/m daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions) followed by maintenance TEMODAR for 6 cycles. Focal RT includes the tumor bed or resection site with a 2- to 3-cm margin. No dose reductions are recommended during the concomitant phase; however, dose interruptions or discontinuation may occur based on toxicity. The TEMODAR dose should be continued throughout the 42-day concomitant period up to 49 days if all of the following conditions are met: absolute neutrophil count ≥1.5 × 10/L, platelet count ≥100 × 10/L, common toxicity criteria (CTC) nonhematological toxicity ≤Grade 1 (except for alopecia, nausea, and vomiting). During treatment a complete blood count should be obtained weekly. Temozolomide dosing should be interrupted or discontinued during concomitant phase according to the hematological and nonhematological toxicity criteria as noted in Table 1 . PCP prophylaxis is required during the concomitant administration of TEMODAR and radiotherapy and should be continued in patients who develop lymphocytopenia until recovery from lymphocytopenia (CTC Grade ≤1).

TABLE 1: Temozolomide Dosing Interruption or Discontinuation During Concomitant Radiotherapy and Temozolomide
Toxicity TMZ InterruptionTreatment with concomitant TMZ could be continued when all of the following conditions were met: absolute neutrophil count ≥1.5 × 109/L; platelet count ≥100 × 109/L; CTC nonhematological toxicity ≤Grade 1 (except for alopecia, nausea, vomiting). TMZ Discontinuation
TMZ=temozolomide; CTC=Common Toxicity Criteria.
Absolute Neutrophil Count ≥0.5 and <1.5 × 109/L <0.5 × 109/L
Platelet Count ≥10 and <100 × 109/L <10 × 109/L
CTC Nonhematological Toxicity
(except for alopecia, nausea, vomiting)
CTC Grade 2 CTC Grade 3 or 4

Maintenance Phase:

Cycle 1:

Four weeks after completing the TEMODAR+RT phase, TEMODAR is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m once daily for 5 days followed by 23 days without treatment.

Cycles 2–6:

At the start of Cycle 2, the dose can be escalated to 200 mg/m, if the CTC nonhematologic toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea, and vomiting), absolute neutrophil count (ANC) is ≥1.5 × 10/L, and the platelet count is ≥100 × 10/L. The dose remains at 200 mg/m per day for the first 5 days of each subsequent cycle except if toxicity occurs. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.

Dose Reduction or Discontinuation During Maintenance:

Dose reductions during the maintenance phase should be applied according to Tables 2 and 3 .

During treatment, a complete blood count should be obtained on Day 22 (21 days after the first dose of TEMODAR) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 10/L (1500/µL) and the platelet count exceeds 100 × 10/L (100,000/µL). The next cycle of TEMODAR should not be started until the ANC and platelet count exceed these levels. Dose reductions during the next cycle should be based on the lowest blood counts and worst nonhematologic toxicity during the previous cycle. Dose reductions or discontinuations during the maintenance phase should be applied according to Tables 2 and 3 .

TABLE 2: Temozolomide Dose Levels for Maintenance Treatment
Dose Level Dose (mg/m2/day) Remarks
−1 100 Reduction for prior toxicity
0 150 Dose during Cycle 1
1 200 Dose during Cycles 2–6 in absence of toxicity
TABLE 3: Temozolomide Dose Reduction or Discontinuation During Maintenance Treatment
Toxicity Reduce TMZ by 1 Dose LevelTMZ dose levels are listed in Table 2 . Discontinue TMZ
TMZ=temozolomide; CTC=Common Toxicity Criteria.
Absolute Neutrophil Count <1.0 × 109/L See footnote TMZ is to be discontinued if dose reduction to <100 mg/m2 is required or if the same Grade 3 nonhematological toxicity (except for alopecia, nausea, vomiting) recurs after dose reduction.
Platelet Count <50 × 109/L See footnote
CTC Nonhematological Toxicity
(except for alopecia, nausea, vomiting)
CTC Grade 3 CTC Grade 4

Patients with Refractory Anaplastic Astrocytoma:

For adults the initial dose is 150 mg/m once daily for 5 consecutive days per 28-day treatment cycle. For adult patients, if both the nadir and day of dosing (Day 29, Day 1 of next cycle) ANC are ≥1.5 × 10/L (1500/µL) and both the nadir and Day 29, Day 1 of next cycle platelet counts are ≥100 × 10/L (100,000/µL), the TEMODAR dose may be increased to 200 mg/m/day for 5 consecutive days per 28-day treatment cycle. During treatment, a complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 10/L (1500/µL) and the platelet count exceeds 100 × 10/L (100,000/µL). The next cycle of TEMODAR should not be started until the ANC and platelet count exceed these levels. If the ANC falls to <1.0 × 10/L (1000/µL) or the platelet count is <50 × 10/L (50,000/µL) during any cycle, the next cycle should be reduced by 50 mg/m, but not below 100 mg/m, the lowest recommended dose (see Table 4 ). TEMODAR therapy can be continued until disease progression. In the clinical trial, treatment could be continued for a maximum of 2 years, but the optimum duration of therapy is not known.

TABLE 4: Dosing Modification Table
TABLE 5: Daily Dose Calculations by Body Surface Area (BSA)
Total BSA
(m2)
75 mg/m2
(mg daily)
150 mg/m2
(mg daily)
200 mg/m2
(mg daily)
1.0 75 150 200
1.1 82.5 165 220
1.2 90 180 240
1.3 97.5 195 260
1.4 105 210 280
1.5 112.5 225 300
1.6 120 240 320
1.7 127.5 255 340
1.8 135 270 360
1.9 142.5 285 380
2.0 150 300 400
2.1 157.5 315 420
2.2 165 330 440
2.3 172.5 345 460
2.4 180 360 480
2.5 187.5 375 500
TABLE 6: Suggested Capsule Combinations Based on Daily Dose in Adults
Number of Daily Capsules by Strength (mg)
Total Daily Dose (mg) 250 mg 180 mg 140 mg 100 mg 20 mg 5 mg
75 0 0 0 0 3 3
82.5 0 0 0 0 4 0
90 0 0 0 0 4 2
97.5 0 0 0 1 0 0
105 0 0 0 1 0 1
112.5 0 0 0 1 0 2
120 0 0 0 1 1 0
127.5 0 0 0 1 1 1
135 0 0 0 1 1 3
142.5 0 0 1 0 0 0
150 0 0 1 0 0 2
157.5 0 0 1 0 1 0
165 0 0 1 0 1 1
172.5 0 0 1 0 1 2
180 0 1 0 0 0 0
187.5 0 1 0 0 0 1
195 0 1 0 0 0 3
200 0 1 0 0 1 0
210 0 0 0 2 0 2
220 0 0 0 2 1 0
225 0 0 0 2 1 1
240 0 0 1 1 0 0
255 1 0 0 0 0 1
260 1 0 0 0 0 2
270 1 0 0 0 1 0
280 0 0 2 0 0 0
285 0 0 2 0 0 1
300 0 0 0 3 0 0
315 0 0 0 3 0 3
320 0 1 1 0 0 0
330 0 1 1 0 0 2
340 0 1 1 0 1 0
345 0 1 1 0 1 1
360 0 2 0 0 0 0
375 0 2 0 0 0 3
380 0 1 0 2 0 0
400 0 0 0 4 0 0
420 0 0 3 0 0 0
440 0 0 3 0 1 0
460 0 2 0 1 0 0
480 0 1 0 3 0 0
500 2 0 0 0 0 0

TEMODAR Capsules:

In clinical trials, TEMODAR was administered under both fasting and nonfasting conditions; however, absorption is affected by food [see Clinical Pharmacology (12)], and consistency of administration with respect to food is recommended. There are no dietary restrictions with TEMODAR. To reduce nausea and vomiting, TEMODAR should be taken on an empty stomach. Bedtime administration may be advised. Antiemetic therapy may be administered prior to and/or following administration of TEMODAR.

TEMODAR (temozolomide) Capsules should not be opened or chewed. They should be swallowed whole with a glass of water.

If capsules are accidentally opened or damaged, precautions should be taken to avoid inhalation or contact with the skin or mucous membranes [see How Supplied/Storage and Handling (16.1)].

TEMODAR for Injection:

Each vial of TEMODAR for Injection contains sterile and pyrogen-free temozolomide lyophilized powder. When reconstituted with 41 mL Sterile Water for Injection, the resulting solution will contain 2.5 mg/mL temozolomide. Bring the vial to room temperature prior to reconstitution with Sterile Water for Injection. The vials should be gently swirled and not shaken. Vials should be inspected, and any vial containing visible particulate matter should not be used. Do not further dilute the reconstituted solution. After reconstitution, store at room temperature (25°C [77°F]). Reconstituted product must be used within 14 hours, including infusion time.

Using aseptic technique, withdraw up to 40 mL from each vial to make up the total dose based on Table 5 above and transfer into an empty 250 mL infusion bag. TEMODAR for Injection should be infused intravenously using a pump over a period of 90 minutes. TEMODAR for Injection should be administered only by intravenous infusion. Flush the lines before and after each TEMODAR infusion.

TEMODAR for Injection may be administered in the same intravenous line with 0.9% Sodium Chloride injection only.

Because no data are available on the compatibility of TEMODAR for Injection with other intravenous substances or additives, other medications should not be infused simultaneously through the same intravenous line.

TEMODAR (temozolomide) is contraindicated in patients who have a history of hypersensitivity reaction (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components. TEMODAR is also contraindicated in patients who have a history of hypersensitivity to DTIC, since both drugs are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC).

Patients treated with TEMODAR may experience myelosuppression, including prolonged pancytopenia, which may result in aplastic anemia, which in some cases has resulted in a fatal outcome. In some cases, exposure to concomitant medications associated with aplastic anemia, including carbamazepine, phenytoin, and sulfamethoxazole/trimethoprim, complicates assessment. Prior to dosing, patients must have an absolute neutrophil count (ANC) ≥1.5 × 10/L and a platelet count ≥100 × 10/L. A complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 10/L and platelet count exceeds 100 × 10/L. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression.

Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed.

For treatment of newly diagnosed glioblastoma multiforme: Prophylaxis against Pneumocystis carinii pneumonia is required for all patients receiving concomitant TEMODAR and radiotherapy for the 42-day regimen.

There may be a higher occurrence of PCP when temozolomide is administered during a longer dosing regimen. However, all patients receiving temozolomide, particularly patients receiving steroids, should be observed closely for the development of PCP regardless of the regimen.

For the concomitant treatment phase with RT, a complete blood count should be obtained prior to initiation of treatment and weekly during treatment.

For the 28-day treatment cycles, a complete blood count should be obtained prior to treatment on Day 1 and on Day 22 (21 days after the first dose) of each cycle. Blood counts should be performed weekly until recovery if the ANC falls below 1.5 × 10/L and the platelet count falls below 100 × 10/L [see Recommended Dosing and Dose Modification Guidelines (2.1)].

TEMODAR can cause fetal harm when administered to a pregnant woman. Administration of TEMODAR to rats and rabbits during organogenesis at 0.38 and 0.75 times the maximum recommended human dose (75 and 150 mg/m), respectively, caused numerous fetal malformations of the external organs, soft tissues, and skeleton in both species [see Use in Specific Populations (8.1)].

As bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes, infusion over a shorter or longer period of time may result in suboptimal dosing. Additionally, the possibility of an increase in infusion-related adverse reactions cannot be ruled out.

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 Multiforme:

During the concomitant phase (TEMODAR+radiotherapy), adverse reactions including thrombocytopenia, nausea, vomiting, anorexia, and constipation were more frequent in the TEMODAR+RT arm. The incidence of other adverse reactions was comparable in the two arms. The most common adverse reactions across the cumulative TEMODAR experience were alopecia, nausea, vomiting, anorexia, headache, and constipation (see Table 7 ). Forty-nine percent (49%) of patients treated with TEMODAR reported one or more severe or life-threatening reactions, most commonly fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%). Overall, the pattern of reactions during the maintenance phase was consistent with the known safety profile of TEMODAR.

Myelosuppression (neutropenia and thrombocytopenia), which is a known dose-limiting toxicity for most cytotoxic agents, including TEMODAR, was observed. When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of the patients, and Grade 3 or Grade 4 platelet abnormalities, including thrombocytopenic reactions, were observed in 14% of the patients treated with TEMODAR.

Manufacturer

Schering Corporation

Active Ingredients

Source

Drugs and Medications [1 Associated Drugs and Medications listed on BioPortfolio]

Temodar [Physicians Total Care, Inc.]

These highlights do not include all the information needed to use TEMODAR safely and effectively. See full prescribing information for TEMODAR. TEMODAR (temozolomide) CapsulesTEMODAR (temozolomide) fo...

Clinical Trials [30 Associated Clinical Trials listed on BioPortfolio]

Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas

Objectives: To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar pl...

Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma

This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a sta...

Sarasar and Temodar for Glioblastoma Multiforme Patients

Primary Objectives: - To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule. - ...

PH I Addition of Farnesyl Transferase Inhibitor to Temozolomide for Pts w Gr 3 & 4 Malignant Gliomas

Objectives: To determine maximum tolerated dose of farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®. To characterize any toxicity associated w combo of far...

Taxotere/Temodar/Cisplatin Study in Melanoma Patients

Primary Objective: 1. To determine the maximum tolerated dose of chemotherapy using Taxotere, Temodar, Cisplatin (TTC) in patients with metastatic melanoma. Secondary Objectives: ...

PubMed Articles [0 Results]

None

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...


Drugs and Medication Quicklinks


Searches Linking to this Drug Record

TABLE 7: Number (%) of Patients with Adverse Reactions: All and Severe/Life Threatening (Incidence of 5% or Greater)
Concomitant Phase
RT Alone
(n=285)
Concomitant Phase
RT+TMZ
(n=288)One patient who was randomized to RT only arm received RT+temozolomide.
Maintenance Phase
TMZ
(n=224)
All Grade ≥3 All Grade ≥3 All Grade ≥3
RT+TMZ=radiotherapy plus temozolomide; NOS=not otherwise specified.
Note: Grade 5 (fatal) adverse reactions are included in the Grade ≥3 column.
Subjects Reporting any Adverse Reaction 258  (91) 74  (26) 266  (92) 80  (28) 206  (92) 82  (37)
Body as a Whole - General Disorders
Anorexia 25  (9) (<1) 56  (19) (1) 61  (27) (1)
Dizziness 10  (4) 12  (4) (1) 12  (5)
Fatigue 139  (49) 15  (5) 156  (54) 19  (7) 137  (61) 20  (9)
Headache 49  (17) 11  (4) 56  (19) (2) 51  (23) (4)
Weakness (3) (1) 10  (3) (2) 16  (7) (2)
Central and Peripheral Nervous System Disorders
Confusion 12  (4) (2) 11  (4) (1) 12  (5) (2)
Convulsions 20  (7) (3) 17  (6) 10  (3) 25  (11) (3)
Memory Impairment 12  (4) (<1) (3) (<1) 16  (7) (1)
Disorders of the Eye
Vision Blurred