Temonix Capsule

Newly Diagnosed Glioblastoma Multiforme: Temonix is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

Refractory Anaplastic Astrocytoma: Temonix 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.

Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound Methyl Triazen Imidazole Carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA. Alkylation (methylation) occurs mainly at the 0 6 and N 7 positions of guanine.

Newly Diagnosed GBM: 75 mg/m² for 42 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m² once daily for Days 1-5 of a 28-day cycle of Temozolomide for 6 cycles.

Refractory Anaplastic Astrocytoma: Initial dose 150 mg/m² once daily for 5 consecutive days per 28-day treatment cycle.

Should be taken on an empty stomach. Take at least 1 hr before meals.

Valproic Acid: Administration of valproic acid decreases oral clearance of Temonix by about 5%. The clinical implication of this effect is not known.

Temozolomide is contraindicated in patients who have a history of hypersensitivity reaction to any of its components. Temozolomide 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).

The most common adverse effects are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, convulsions, rash, hemiparesis, diarrhea, asthenia, fever, dizziness, coordination abnormal, viral infection, amnesia, and insomnia. The most common Grade 3 to 4 hematologic labcratory abnormalities that have developed during treatment with Temonix are: lymphopenia, thrombocytopenia, neutropenia, and leukopenia. Allergic reactions have also been reported.

Pregnancy Category D. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Temozolomide. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and tumorigenicity shown for Temozolomide in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother from Temozolomide.

Myelosuppression: monitor Absolute Neutrophil Count (ANC) and platelet count prior to dosing and throughout treatment. Geriatric patients and women have a higher risk of developing myelosuppression. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed.

Pneumocystis carinii pneumonia (PCP): prophylaxis required for all patients receiving concomitant Temonix and radiotherapy for the 42-day regimen for the treatment of newly diagnosed glioblastoma multiforme. All patients, particularly those receiving steroids, should be observed closely for the development of lymphopenia and PCP. Complete blood counts should be obtained throughout the treatment course as specified. Fetal harm can occur when administered to a pregnant woman. Women should be advised to avoid becoming pregnant when receiving Temonix.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Renal Impairment: Caution should be exercised when Temonix is administered to patients with severe renal impairment.

Hepatic Impairment: Caution should be exercised when Temonix is administered to patients with severe hepatic impairment.

Doses of 500, 750, 1000, and 1250 mg/m² (total dose per cycle over 5 days) have been evaluated clinically in patients. Dose-limiting toxicity was hematologic and was reported with any dose but is expected to be more severe at higher doses. An overdose of 2000 mg per day for 5 days was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi-organ failure, and death. There are reports of patients who have taken more than 5 days of treatment (up to 64 days), with adverse reactions reported including bone marrow suppression, which in some cases was severe and prolonged, and infections and resulted in death. In the event of an overdose, hematologic evaluation is needed. Supportive measures should be provided as necessary.

Cytotoxic Chemotherapy

Store at a temperature not exceeding 25°C in a dry place. Protect from light and moisture. Do not freeze.