Temodar Injection

— THERAPEUTIC CATEGORIES —
  • CNS cancers

Temodar Injection Generic Name & Formulations

General Description

Temozolomide 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol.

Pharmacological Class

Alkylating agent.

See Also

How Supplied

Caps—Contact supplier; Single-use vials—1

Manufacturer

Generic Availability

YES

Mechanism of Action

Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA, resulting in programmed cell death.

Temodar Injection Indications

Indications

Newly diagnosed glioblastoma multiforme. Adjuvant treatment of newly diagnosed anaplastic astrocytoma. Refractory anaplastic astrocytoma.

Temodar Injection Dosage and Administration

Adult

See full labeling for monitoring and dose adjustment guidelines. IV: Infuse over 90mins. Oral caps: Swallow whole with water; take on empty stomach or at bedtime to reduce nausea/vomiting, pre- and post-treat with antiemetics. Newly diagnosed glioma: Concomitant use phase: 75mg/m2 (orally or by IV) once daily for 42–49 days with focal radiotherapy. Maintenance use phase (Cycle 1): start 4wks after the concomitant use phase, 150mg/m2 (orally or by IV) once daily on Days 1–5 of each 28-day treatment cycle; (Cycles 2 through 6): may increase to 200mg/m2 once daily on Days 1–5 if no interruptions/discontinuations required (if dose was not escalated at onset of Cycle 2, do not increase dose during Cycles 3–6). Adjuvant treatment of newly diagnosed anaplastic astrocytoma (Cycle 1): start 4wks after the end of radiotherapy, 150mg/m2 (orally) once daily on Days 1–5 of each 28-day treatment cycle; (Cycles 2 through 12): increase to 200mg/m2 once daily on Days 1–5 if tolerated in Cycle 1 (if dose was not escalated at onset of Cycle 2, do not increase dose during Cycles 3–6). Refractory anaplastic astrocytoma: initially 150mg/m2 once daily on Days 1–5 of each 28-day treatment cycle; increase to 200mg/m2 per day if ANC ≥1.5×109/L and platelets ≥100×109/L are reached at the nadir and on Day 1 of the next cycle; continue until disease progression or unacceptable toxicity. 

Children

Not established.

Temodar Injection Contraindications

Contraindications

Hypersensitivity to dacarbazine.

Temodar Injection Boxed Warnings

Not Applicable

Temodar Injection Warnings/Precautions

Warnings/Precautions

Myelosuppression (higher risk in women or elderly, esp. in 1st cycle). Do not begin therapy until ANC ≥1.5×109/L and platelets ≥100×109/L prior to dosing. Obtain CBCs prior to treatment initiation and on Day 22 of each cycle; repeat weekly until recovery if ANC or platelets fall below acceptable limits. When concomitant with radiotherapy, obtain CBCs prior to initiation, weekly during therapy, and as indicated. Perform LFTs at baseline, midway through Cycle 1, prior to each subsequent cycle, and 2–4wks after the last dose. Glioblastoma: monitor for and provide prophylaxis against P. carinii pneumonia (PCP) during the concomitant phase. ESRD on dialysis, severe renal (CrCl <36mL/min/m2) or hepatic impairment. Avoid inhalation, and skin/mucous membrane contact, of capsule contents. Elderly. Embryo-fetal toxicity. Advise to use effective contraception during and for 6 months (females of reproductive potential) and for 3 months (males w females partners) after the last dose. Male patients should not donate semen during and for 3 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).

Temodar Injection Pharmacokinetics

Absorption

Median Tmax: 1 hour.

Effect of food: temozolomide Cmax and AUC decreased when administered after a modified high-fat breakfast.

Distribution

Mean apparent volume of distribution: 0.4 L/kg.

Metabolism

Hepatic.

Elimination

Renal. Half-life: 1.8 hours. Clearance: ~5.5 L/hr/m2.

Temodar Injection Interactions

Interactions

Concomitant carbamazepine, phenytoin, sulfamethoxazole/trimethoprim may complicate myelosuppression assessment. May be potentiated by valproic acid.

Temodar Injection Adverse Reactions

Adverse Reactions

Alopecia, fatigue, nausea, vomiting, anorexia, constipation, headache, convulsions, rash, hemiparesis, diarrhea, asthenia, fever, dizziness, abnormal coordination, viral infection, amnesia, insomnia, edema; myelosuppression (may be dose-limiting; see full labeling), hepatotoxicity (may be fatal), secondary malignancies (eg, myelodysplastic syndrome, myeloid leukemia).

Temodar Injection Clinical Trials

See Literature

Temodar Injection Note

Not Applicable

Temodar Injection Patient Counseling

See Literature