Instructions for Temozolomide

1. All names: temozolomide, Temozolomide, Taidao, Temodal, Mercer, TEMODAR

2. Indications:

1. Newly diagnosed glioblastoma: Temozolomide is suitable for the treatment of adult patients newly diagnosed with glioblastoma, along with radiotherapy and then as maintenance treatment.

2. Anaplastic astrocytoma: Temozolomide is suitable for the adjuvant treatment of newly diagnosed adult anaplastic astrocytoma and the treatment of adult refractory anaplastic astrocytoma.

3. Usage and dosage:

1. Monitor to inform dosage and administration:

(1) Prior to administration, temozolomide needs to be discontinued until the patient's absolute neutrophil count (ANC) is 1.5x109/L or higher and the platelet count is 100x109g/L or higher.

(2) For concomitant radiation therapy, perform a complete blood count before starting treatment and weekly during treatment.

(3) For 28-day treatment cycles, obtain a complete blood count before treatment on Days 1 and 22 of each cycle. If ANC is less than 1.5x109/L and platelet count is less than 100x109/L, perform a complete blood count weekly until recovery.

(4) For patients receiving concomitant focal radiation therapy, a complete blood count should be obtained weekly as clinically indicated.

2. Recommended dosage for newly diagnosed glioblastoma:

(1) Temozolomide is administered orally or intravenously once daily during concurrent use with focal radiotherapy for 42 to 49 days, and then once daily during the maintenance phase on days 1 to 5 of each 28-day cycle for a total of 6 cycles. Provide Pneumocystis pneumonia (PCP) prophylaxis during the combination phase and continue in patients who develop lymphopenia until remission to Grade 1 or less.

(2) Concomitant use phase:The recommended dose of temozolomide is 75mg/m2, taken orally or intravenously, once a day for 42-49 days, in combination with lesion radiotherapy. Local radiation therapy covers the tumor bed or resection site, with a margin of 2-3 cm. Perform a complete blood count weekly.

(3) Single-agent maintenance phase: Beginning 4 weeks after the completion of the concomitant phase, temozolomide is administered orally or intravenously once daily on days 1-5 of each 28-day cycle for 6 cycles.The recommended dose of temozolomide in the maintenance phase is 150 mg/m2 per day on days 1-5 of the first cycle. If there is no need to interrupt or stop the administration, it can be increased to 200 mg/m2 per day on days 1-5 before the start of the second cycle. If the dose is not increased at the beginning of Cycle 2, do not increase the dose for Cycles 3-6.

3. Recommended dose for anaplastic astrocytoma:

(1) Adjuvant treatment of newly diagnosed anaplastic astrocytoma: A single oral dose of temozolomide on days 1-5 of a 28-day cycle starting 4 weeks after the end of radiation therapy for 12 cycles. The recommended dose of temozolomide is 150 mg/m2 daily on days 1-5 of cycle 1, or 200 mg/m2 daily on days 1-5 if the patient has no or minimal toxicity in cycle 1. If the dose is not increased at the beginning of Cycle 2, do not increase the dose during Cycles 3-6.

(2) Refractory anaplastic astrocytoma:The recommended initial dose of temozolomide is 150 mg/m2 once daily on days 1-5 of each 28-day cycle. Increase the temozolomide dose to 200 mg/m2 per day if the following conditions are met at nadir: ANC ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L. Temozolomide is usually continued until disease progression or unacceptable toxicity occurs.

Perform a complete blood count on day and then weekly until ANC >1.5×109/L and platelet count >100×109/L. Do not start the next cycle until the ANC and platelet count exceed these levels.

4. Dose adjustment: If ANC <1×109/L or platelet count <50×109/L in any cycle, reduce the dose of temozolomide in the next cycle by 50 mg/m2/day. Permanently discontinue temozolomide in patients who cannot tolerate a daily dose of 100 mg/m2.

5. Management: Take temozolomide capsules at the same time every day. With regard to food (fasted and non-fasted), administer temozolomide consistently. To reduce nausea and vomiting, take temozolomide on an empty stomach or at bedtime, and consider antiemetic treatment before and after administration. Swallow the temozolomide capsules with water. Patients should not open, chew, or dissolve capsule contents.

4. Adverse reactions:

In clinical studies of newly diagnosed glioblastoma, the most common adverse reactions (≥20%) were alopecia, fatigue, nausea, anorexia, headache, constipation, and vomiting; In clinical studies of refractory anaplastic astrocytoma, the most common adverse reactions (≥20%) were nausea, vomiting, headache, fatigue, constipation and convulsions. Adverse reactions reported with temozolomide for injection include pain, irritation, pruritus, fever, swelling, and infusion site erythema, petechiae, and hematoma.

Toxic epidermal necrolysis and Stevens-Johnson syndrome, erythema multiforme, aplastic anemia (including fatal), fatal and severe hepatotoxicity have occurred since the release of temozolomide Adverse events include sex, elevated liver enzymes, hyperbilirubinemia, cholestasis and hepatitis, serious opportunistic infections with bacteria, viruses (primary and reactivated), fungi and protozoan organisms, interstitial pneumonia, pneumonia, alveolitis and pulmonary fibrosis, diabetes insipidus.

5. Storage:

1. Store temozolomide capsules at 25°C (77°F); the allowable deviation is 15°C to 30°C (59°F to 86°F). If capsules are accidentally opened or damaged, take precautions to avoid inhalation or contact with skin or mucous membranes. If contact with powder occurs, wash affected area immediately with water.

2. Temozolomide for injection will be packaged in single-dose glass bottles containing 100 mg of temozolomide and will be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Store reconstituted temozolomide solution at room temperature (25°C [77°F]) and discard reconstituted solution if not used within 14 hours, including the time of infusion.

6. Taboo:

Temozolomide is contraindicated in patients with a history of severe allergic reactions such as:

(1) Including temozolomide and any other ingredients thereof;

(2) Dacarbazine (dacarbazine), because both temozolomide and dacarbazine are metabolized into the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide.

7. Mechanism of action:

Temozolomideis not directly active, but is rapidly non-enzymatically converted to the active compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC) at physiological pH. The cytotoxicity of MTIC is believed to be mainly due to DNA alkylation, mainly at the O6 and N7 positions of guanine, which causes DNA double-strand breaks and leads to programmed cell death.

The original drug temozolomide has been launched in China and has entered the scope of Class B medical insurance. The price of a common specification100mg*1 tablet*5 bags per box may be around 2,000 RMB. Temozolomide generic drugs price listed overseasIt is relatively low, and its drug ingredients are basically the same as those of the original drug of temozolomide. For example, the price of 100mg*5 per box produced by a Bangladesh pharmaceutical factory may be around a few hundred yuan (the price may fluctuate due to exchange rate effects).