TEMODAR- temozolomide capsule
TEMODAR- temozolomide injection, powder, lyophilized, for solution
Merck Sharp & Dohme Corp.
1 INDICATIONS AND USAGE
1.1 Newly Diagnosed Glioblastoma Multiforme
TEMODAR� (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.
1.2 Refractory Anaplastic Astrocytoma
TEMODAR 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.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing and Dose Modification Guidelines
The recommended dose for TEMODAR as an intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes [see Clinical Pharmacology (12.3)]. Dosage of TEMODAR must be adjusted according to nadir neutrophil and platelet counts in the previous cycle and the neutrophil and platelet counts at the time of initiating the next cycle. For TEMODAR dosage calculations based on body surface area (BSA) see Table 5. For suggested capsule combinations on a daily dose.
TEMODAR for Injection:
Each vial of TEMODAR for Injection contains sterile and pyrogen-free temozolomide lyophilized powder. When reconstituted with 41 mL Sterile Water for Injection, the resulting solution will contain 2.5 mg/mL temozolomide. Bring the vial to room temperature prior to reconstitution with Sterile Water for Injection. The vials should be gently swirled and not shaken. Vials should be inspected, and any vial containing visible particulate matter should not be used. Do not further dilute the reconstituted solution. After reconstitution, store at room temperature (25�C [77�F]). Reconstituted product must be used within 14 hours, including infusion time.
TEMODAR (temozolomide) is contraindicated in patients who have a history of hypersensitivity reaction (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components. TEMODAR is also contraindicated in patients who have a history of hypersensitivity to dacarbazine (DTIC), since both drugs are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC)
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.
TEMODAR contains temozolomide, an imidazotetrazine derivative. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-as -tetrazine-8-carboxamide.
The material is a white to light tan/light pink powder with a molecular formula of C6 H6 N6 O2 and a molecular weight of 194.15. The molecule is stable at acidic pH (<5) and labile at pH >7; hence TEMODAR can be administered orally and intravenously. The prodrug, temozolomide, is rapidly hydrolyzed to the active 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) at neutral and alkaline pH values, with hydrolysis taking place even faster at alkaline pH.
PATIENT COUNSELING INFORMATION
See FDA-Approved Patient Labeling (Patient Information).
17.1 Information for the Patient
Physicians should discuss the following with their patients:
Nausea and vomiting are the most frequently occurring adverse reactions. Nausea and vomiting are usually either self-limiting or readily controlled with standard antiemetic therapy.
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.
The medication should be kept away from children and pets.