Generic Name

Temozolomide

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Classification

FDA Approved Indications

• Treatment of adult patients with newly diagnosed glioblastoma multiforme (in combination with radiotherapy)
• Treatment of glioblastoma multiforme (recurrence)
• Treatment of adult patients with refractory anaplastic astrocytoma

Mechanism of Action

Temozolomide is an oral alkylating agent that methylates DNA at the O6 and N7 positions of guanine residues, leading to DNA damage, apoptosis, and cell death, particularly in tumor cells.

Dosage and Administration

Adult: Typically 150-200 mg/m² once daily for 5 days in 28-day cycles, concomitantly with radiotherapy or as monotherapy for recurrent disease, adjusted based on patient tolerance.

Pediatric: Not recommended for pediatric use due to limited data.

Geriatric: No specific dosage adjustment, but caution due to potential increased risk of adverse effects.

Renal Impairment: Use with caution; no specific dose adjustment recommended but monitor closely.

Hepatic Impairment: Use with caution; no specific dose adjustment recommended.

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration.

Distribution: Widely distributed, crosses blood-brain barrier.

Metabolism: Spontaneously hydrolyzed at physiological pH to active metabolite MTIC and then to Breakdown products.

Excretion: Primarily via urine.

Half Life: Approximately 1.8 hours for the parent drug.

Contraindications

• Hypersensitivity to temozolomide or any component.
• Bone marrow suppression with active infection.

Precautions

• Myelosuppression; closely monitor blood counts.
• Infection risk; monitor for signs of infection.
• Pregnancy and lactation; avoid use as teratogenic.

Adverse Reactions - Common

• Myelosuppression (neutropenia, thrombocytopenia, anemia) (Common)
• Nausea and vomiting (Common)
• Fatigue (Common)
• Hair loss (Less common)

Adverse Reactions - Serious

• Severe myelosuppression leading to infection or bleeding (Serious)
• Secondary malignancies (rare) (Rare)
• Liver dysfunction (Rare)

Drug-Drug Interactions

• Cytochrome P450 inducers or inhibitors may affect metabolism.
• Agents causing myelosuppression (e.g., radiation, other chemotherapeutics).

Drug-Food Interactions

• No significant interactions noted.

Drug-Herb Interactions

• Limited data; caution with herbal supplements that affect blood counts or liver enzymes.

Nursing Implications

Patient/Family Teaching

• Report signs of infection, unusual bleeding, or fatigue.
• Use effective contraception during and for at least 6 months after therapy.
• Avoid pregnancy and breastfeeding during treatment.
• Report severe nausea or vomiting; take antiemetics as prescribed.

Special Considerations

Black Box Warnings:

• Myelosuppression may be severe and life-threatening. Regular CBC monitoring is essential.
• Secondary malignancies have been reported.

Genetic Factors: Patients with certain genetic polymorphisms in DNA repair genes may have different responses or risks.

Lab Test Interference: May cause thrombocytopenia and leukopenia, affecting lab tests.

Overdose Management

Signs/Symptoms: Severe myelosuppression, infection, bleeding.

Treatment: Supportive care — hematopoietic growth factors, transfusions, infection management; no specific antidote.

Storage and Handling

Storage: Store at room temperature (20-25°C), protected from light.

Stability: Stable under recommended storage conditions.