TMZ 250 mg

INDICATIONS

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

PHARMACOLOGY

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.

DOSAGE

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.

INTERACTION

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

SIDE EFFECTS

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 Temozolomide are: lymphopenia, thrombocytopenia, neutropenia, and leukopenia. Allergic reactions have also been reported.

PREGNANCY & LACTATION

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.

PRECAUTIONS & WARNINGS

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 Temozolomide 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 Temozolomide.

USE IN SPECIAL POPULATIONS

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.Renal Impairment: Caution should be exercised when Temozolomide is administered to patients with severe renal impairment.Hepatic Impairment: Caution should be exercised when Temozolomide is administered to patients with severe hepatic impairment.

THERAPEUTIC CLASS

Cytotoxic Chemotherapy

STORAGE CONDITIONS

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