Schering-Plough公司的口服细胞毒烷化抗癌剂Temodar(temozolomide，替莫唑胺)(Ⅰ)已获美国FDA批准用于新诊断的多形性成胶质细胞瘤(GBM)，这是一种恶性脑癌。
制造商：先灵葆雅 ( Schering-Plough )
成份：Temozolomide
药品英文名
Temozolomide
药品别名
Temodar
药物剂型
胶囊：5mg，20mg，100mg，250mg。
药理作用
本品是一种前药，直到进入体内水解成MTIC[5-(3-methyltriazen-1yl)imidazole-4-carboxamide]后才具有抗肿瘤活性。
药动学
接受本品后，药物就会在生理pH条件下被非酶水解成MTIC。MTIC通过在DNA中鸟嘌呤的O6和N7位上起到烷化剂作用，产生细胞毒。P450同工酶在本品和MTIC的代谢上仅有极微弱的作用。
适应证
星形细胞瘤。
禁忌证
1.对本品过敏者、哺乳者、骨髓抑制者禁用。
2.对达卡巴嗪过敏者禁用，因该药亦代谢为MTIC(亦有称AIC)。
注意事项
1.老年人、肝肾功能不全者慎用。
2.严重肝肾功能不全者必须谨慎用药。不过，轻中度肝功能受损者的药动学类似肝功能正常者。
3.肌酐清除率为每分钟36～130ml/m2的患者并不影响本品的清除。
4.老年人和女性有较高的骨髓抑制危险性。
5.服药时，应保持胶囊的完整性。
6.本品每天剂量做1次口服，用一整杯开水吞服，而且应始终保持空腹时服药。
不良反应
1.最常见的不良反应有恶心、呕吐、头痛、乏力，往往有自限性；严重者可在服药前先用止吐药。
2.骨髓抑制，中性粒细胞和血小板减少是使剂量受限的毒性。在用药后的第26天血小板数达到最低值，第28天中性粒细胞达到最低值。一般在14天内恢复。
3.动物试验证实，可致畸和发生胎儿死亡。
用法用量
1.治疗成人难治的退行性星形细胞瘤，每天可给予150mg/m2，连用5天，28天1个疗程。根据血小板和绝对中性粒细胞的最低值调整剂量，在开始用药的第22天(即首剂后的21天)或者这一日的48h以内检查血小板数和绝对中性粒细胞数作为调整的依据，并每周复查1次，直至两种细胞数分别超过了1500和100000/mm3。下一个疗程一直要等到两种细胞确已超过以上数据。如果确已超过，第2个疗程的剂量就可增至每天200mg/m2，仍连用5天，28天1个疗程。在任一疗程中，如以上两种数据分别在1000～1500和50000～100000/mm3，疗程就应延长，直至恢复到超过两种原有的数据，这时，仍采用每天150mg/m2，连用5天；如两种数据分别降至＜1000和＜5000/mm3，剂量就降至每天50mg/m2，如不少于这两个最低值，就可给予每天100mg/m2。2.治疗可能持续到疾病已有所减轻。已有用药两年的病例，但最佳疗程尚待确定。
药物相应作用
丙戊酸可使本品的清除减少5%。
专家点评
本品为新的星形细胞瘤治疗药，对脑胶质细胞瘤有一定的疗效，但由于本品上市时间短，最佳疗程尚待确定
Individually wrapped, single-dose sachets designed to remain sealed until use
Color coded to aid in dispensing the prescribed dose
Fold over at ridged notch and tear to open sachets and dispense capsules.
Indication
TEMODAR® (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.
Selected Important Safety Information
TEMODAR is contraindicated in patients who have a history of hypersensitivity (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components, or to dacarbazine (DTIC).
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. 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 also been observed.
Prophylaxis against Pneumocystis carinii pneumonia (PCP) 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.
TEMODAR can cause fetal harm when administered to a pregnant woman. In nursing women, a decision should be made whether to discontinue nursing or to discontinue TEMODAR, taking into account the importance of the drug to the mother. The safety and effectiveness of TEMODAR in children have not been established.
As bioequivalence between TEMODAR Capsules and TEMODAR for Injection 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.
TEMODAR Capsules should not be opened or chewed. 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.
Caution should be exercised when administered to those with severe hepatic or renal impairment.
The adverse event profile was similar in patients <65 years of age and those > 65 years.
The most common adverse reactions in clinical studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were alopecia 69%, 55%; fatigue 54%, 61%; nausea 36%, 49%; vomiting 20%, 29%; anorexia 19%, 27%; headache 19%, 23%; rash 19%, 13%; constipation 18%, 22%; with the following important adverse events also reported: convulsions 6%, 11% and thrombocytopenia 4%, 8%.
Of these adverse events, those Grade > 3 in clinical studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were fatigue 7%, 9%; nausea 1%, 1%; vomiting <1%, 2%; anorexia 1%, 1%; headache 2%, 4%; rash 1%, 1%; constipation 1%, 0%; convulsions 3%, 3%; thrombocytopenia 3%, 4%.
When laboratory abnormalities and adverse events were combined, Grade 3 or 4 neutropenia occurred in 8% and Grade 3 or 4 platelet abnormalities, including thrombocytopenic events, occurred in 14% of patients treated with temozolomide.
Adverse reactions reported from intravenous formulation studies that were not reported in TEMODAR Capsule studies were: pain, irritation, pruritus, warmth, swelling, and erythema at infusion site as well as the following adverse reactions: petechiae and hematoma.
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附件:
201081519004221.pdf
