TEMODAL

What it is

TEMODAL is temozolomide, supplied in capsules containing 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg of the active ingredient. TEMODAL is an imidazotetrazine alkylating agent with antitumour activity that undergoes rapid chemical conversion in the systemic circulation at physiological pH to the active compound, monomethyl triazeno imidazole carboxamide (MTIC).

Approved indications

— Treatment of patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as adjuvant treatment. — Recurrence of anaplastic astrocytoma and glioblastoma multiforme following standard therapy. — First line treatment for patients with advanced metastatic malignant melanoma.

Dosing overview

For newly diagnosed glioblastoma multiforme, TEMODAL is administered orally at 75 mg/m² daily for 42 days concomitant with focal radiotherapy. In the adjuvant phase, dosage in Cycle 1 is 150 mg/m² once daily for 5 days followed by 23 days without treatment. At the start of Cycle 2, the dose is escalated to 200 mg/m² if toxicity criteria are met. For recurrent glioblastoma multiforme or anaplastic astrocytoma in chemotherapy-naive patients, TEMODAL is administered orally at a dose of 200 mg/m² once daily for 5 days per 28-day cycle. For those previously treated with chemotherapy, the initial dose is 150 mg/m² once daily, to be increased in the second cycle to 200 mg/m² daily providing haematological parameters are met. For patients with metastatic malignant melanoma, the recommended dose is 200 mg/m² once daily for 5 days per 28-day cycle.

Key safety warnings

Prophylaxis against Pneumocystis carinii pneumonia is required for all patients receiving concomitant TEMODAL and radiotherapy for the 42 day regimen (with a maximum of 49 days) regardless of lymphocyte count. Hepatic injury, including fatal hepatic failure, has been reported very rarely in patients treated with temozolomide. Baseline liver function tests should be performed prior to treatment initiation. If abnormal, physicians should assess the benefit/risk prior to initiating temozolomide including the potential for fatal hepatic failure. Hepatitis due to hepatitis B virus (HBV) reactivation, in some cases resulting in death, has been reported. Patients should be screened for HBV infection before treatment initiation. Patients with evidence of prior HBV infection should be monitored for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment with TEMODAL. Temozolomide causes myelosuppression. Patients treated with temozolomide may also experience prolonged pancytopenia. This may result in aplastic anaemia, which in some cases has resulted in a fatal outcome.

Contraindications

TEMODAL is contraindicated in patients who have a history of hypersensitivity reaction to its components or to dacarbazine (DTIC). TEMODAL is contraindicated for use during pregnancy and in women who intend to become pregnant. TEMODAL must not be used by breastfeeding women. TEMODAL is contraindicated in patients with severe myelosuppression.

PBS listing

TEMODAL is listed on the PBS in 100 mg and 140 mg capsule strengths. The 100 mg strength has 2 PBS items with restricted access at an ex-manufacturer price of A$48.19, and the 140 mg strength has 2 PBS items with restricted access at an ex-manufacturer price of A$66.46.

Regulatory history

TEMODAL was first approved on 30 June 1999. ARTG registration for TEMODAL capsules across six strengths (5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg) was first listed on 13 November 2009 under licence category RE.