INDICATIONS AND USAGE
TEMODAR (temozolomide) Capsules are indicated for the treatment of adult patients with refractory anaplastic astrocytoma, ie, patients at first relapse who have experienced disease progression on a drug regimen containing a nitrosourea and procarbazine.
This indication is based on the response rate in the indicated population. No results are available from randomized controlled trials in recurrent anaplastic astrocytoma that demonstrate a clinical benefit resulting from treatment, such as improvement in disease-related symptoms, delayed disease progression, or improved survival.
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DOSAGE AND ADMINISTRATION
Dosage of TEMODAR must be adjusted according to nadir neutrophil and platelet counts in the previous cycle and neutrophil and platelet counts at the time of initiating the next cycle. The initial dose is 150 mg/m2 orally once daily for 5 consecutive days per 28-day treatment cycle. If both the nadir and day of dosing (Day 29, Day 1 of next cycle) absolute neutrophil counts (ANC) are >/=1.5 × 109/L (1,500/µL) and both the nadir and Day 29, Day 1 of next cycle platelet counts are >/=100 × 109/L (100,000/µL), the TEMODAR dose may be increased to 200 mg/m2/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 × 109/L (1,500/µL) and the platelet count exceeds 100 × 109/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 × 109/L (1,000/µL) or the platelet count is <50 × 109/L (50,000/µL) during any cycle, the next cycle should be reduced by 50 mg/m2, but not below 100 mg/m2, the lowest recommended dose (see Table 4) (see WARNINGS).
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. For TEMODAR dosage calculations based on body surface area (BSA), see Table 5. For suggested capsule combinations based on daily dose, see Table 6.
Table 5
Daily Dose Calculations by Body Surface Area (BSA)
for 5 consecutive days per 28-day treatment cycle for
the initial chemotherapy cycle (150 mg/m2) and for
subsequent chemotherapy cycles (200 mg/m2) for
patients whose nadir and day of dosing (Day 29, Day 1
of next cycle) absolute neutrophil count (ANC) is >1.5
× 109/L (1,500/µL) and whose nadir and Day 29, Day 1
of next cycle platelet count is >100 × 109/L (100,000/µL).
Total BSA
(m2) |
150 mg/m2 (mg daily) |
200 mg/m2 (mg daily) |
|
0.5
|
75
|
100
|
|
0.6
|
90
|
120
|
|
0.7
|
105
|
140
|
|
0.8
|
120
|
160
|
|
0.9
|
135
|
180
|
|
1.0
|
150
|
200
|
|
1.1
|
165
|
220
|
|
1.2
|
180
|
240
|
|
1.3
|
195
|
260
|
|
1.4
|
210
|
280
|
|
1.5
|
225
|
300
|
|
1.6
|
240
|
320
|
|
1.7
|
255
|
340
|
|
1.8
|
270
|
360
|
|
1.9
|
285
|
380
|
|
2.0
|
300
|
400
|
|
2.1
|
315
|
420
|
|
2.2
|
330
|
440
|
|
2.3
|
345
|
460
|
|
2.4
|
360
|
480
|
|
2.5
|
375
|
500
|
|
Table 6
| Suggested Capsule Combinations Based on Daily Dose |
|
|
Number of Daily Capsules by Strength (mg) |
| Total Daily Dose (mg) |
250 |
100 |
20 |
5 |
|
200
|
0
|
2
|
0
|
0
|
|
205
|
0
|
2
|
0
|
1
|
|
210
|
0
|
2
|
0
|
2
|
|
215
|
0
|
2
|
0
|
3
|
|
220
|
0
|
2
|
1
|
0
|
|
225
|
0
|
2
|
1
|
1
|
|
230
|
0
|
2
|
1
|
2
|
|
235
|
0
|
2
|
1
|
3
|
|
240
|
0
|
2
|
2
|
0
|
|
245
|
0
|
2
|
2
|
1
|
|
250
|
1
|
0
|
0
|
0
|
|
255
|
1
|
0
|
0
|
1
|
|
260
|
1
|
0
|
0
|
2
|
|
265
|
1
|
0
|
0
|
3
|
|
270
|
1
|
0
|
1
|
0
|
|
275
|
1
|
0
|
1
|
1
|
|
280
|
1
|
0
|
1
|
2
|
|
285
|
1
|
0
|
1
|
3
|
|
290
|
1
|
0
|
2
|
0
|
|
295
|
1
|
0
|
2
|
1
|
|
300
|
0
|
3
|
0
|
0
|
|
305
|
0
|
3
|
0
|
1
|
|
310
|
0
|
3
|
0
|
2
|
|
315
|
0
|
3
|
0
|
3
|
|
320
|
0
|
3
|
1
|
0
|
|
325
|
0
|
3
|
1
|
1
|
|
330
|
1
|
0
|
4
|
0
|
|
335
|
1
|
0
|
4
|
1
|
|
340
|
0
|
3
|
2
|
0
|
|
345
|
0
|
3
|
2
|
1
|
|
350
|
1
|
1
|
0
|
0
|
|
355
|
1
|
1
|
0
|
1
|
|
360
|
1
|
1
|
0
|
2
|
|
365
|
1
|
1
|
0
|
3
|
|
370
|
1
|
1
|
1
|
0
|
|
375
|
1
|
1
|
1
|
1
|
|
380
|
1
|
1
|
1
|
2
|
|
385
|
1
|
1
|
1
|
3
|
|
390
|
1
|
1
|
2
|
0
|
|
395
|
1
|
1
|
2
|
1
|
|
400
|
0
|
4
|
0
|
0
|
|
405
|
0
|
4
|
0
|
1
|
|
410
|
0
|
4
|
0
|
2
|
|
415
|
0
|
4
|
0
|
3
|
|
420
|
0
|
4
|
1
|
0
|
|
425
|
0
|
4
|
1
|
1
|
|
430
|
1
|
1
|
4
|
0
|
|
435
|
0
|
4
|
1
|
3
|
|
440
|
0
|
4
|
2
|
0
|
|
445
|
0
|
4
|
2
|
1
|
|
450
|
1
|
2
|
0
|
0
|
|
455
|
1
|
2
|
0
|
1
|
|
460
|
1
|
2
|
0
|
2
|
|
465
|
1
|
2
|
0
|
3
|
|
470
|
1
|
2
|
1
|
0
|
|
475
|
1
|
2
|
1
|
1
|
|
480
|
1
|
2
|
1
|
2
|
|
485
|
1
|
2
|
1
|
3
|
|
490
|
1
|
2
|
2
|
0
|
|
495
|
1
|
2
|
2
|
1
|
|
500
|
2
|
0
|
0
|
0
|
|
In the clinical trial, TEMODAR was administered under both fasting and nonfasting conditions; however, absorption is affected by food (see CLINICAL PHARMACOLOGY) and consistency of administration with respect to food is recommended. There are no dietary restrictions with temozolomide. To reduce nausea and vomiting, temozolomide 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.
Handling and Disposal: Temozolomide causes the rapid appearance of malignant tumors in rats. Capsules should not be opened. If capsules are accidentally opened or damaged, rigorous precautions should be taken with the capsule contents to avoid inhalation or contact with the skin or mucous membranes. Procedures for proper handling and disposal of anticancer drugs should be considered. 1-7 Several guidelines on this subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
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HOW SUPPLIED
TEMODAR (temozolomide) Capsules are supplied in amber glass bottles with child-resistant polypropylene caps containing the following capsule strengths:
TEMODAR (temozolomide) Capsules 5 mg: 5 and 20 capsule bottles.
5 count--NDC 0085-1248-01
20 count--NDC 0085-1248-02
TEMODAR (temozolomide) Capsules 20 mg: 5 and 20 capsule bottles.
5 count--NDC 0085-1244-01
20 count--NDC 0085-1244-02
TEMODAR (temozolomide) Capsules 100 mg: 5 and 20 capsule bottles.
5 count--NDC 0085-1259-01
20 count--NDC 0085-1259-02
TEMODAR (temozolomide) Capsules 250 mg: 5 and 20 capsule bottles.
5 count--NDC 0085-1252-01
20 count--NDC 0085-1252-02
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F).
[See USP Controlled Room Temperature]
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