APO-TEMOZOLOMIDE

What it is

APO-TEMOZOLOMIDE is a capsule formulation of temozolomide available in strengths of 5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg. Temozolomide is an imidazotetrazine alkylating agent with anti-tumour activity. It undergoes rapid chemical conversion in the systemic circulation at physiological pH to the active compound, monomethyl triazeno imidazole carboxamide (MTIC).

Approved indications

— Newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as adjuvant treatment. — Recurrence of anaplastic astrocytoma and glioblastoma multiforme following standard therapy. — Advanced metastatic malignant melanoma as first-line treatment.

Dosing overview

For newly diagnosed glioblastoma multiforme in the concomitant phase, temozolomide is administered orally at 75 mg/m² daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions) followed by adjuvant temozolomide for six cycles. In the adjuvant phase, dosage in cycle 1 is 150 mg/m² once daily for five days followed by 23 days without treatment. At the start of cycle 2, the dose is escalated to 200 mg/m² if specified toxicity criteria are met. For adults with recurrent glioblastoma multiforme or anaplastic astrocytoma previously untreated with chemotherapy, temozolomide is administered orally at a dose of 200 mg/m² once daily for five 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 specified haematological criteria are met. For patients with metastatic malignant melanoma, the recommended dose is 200 mg/m² once daily for five days per 28 day cycle.

Key safety warnings

Patients who received concomitant temozolomide and radiotherapy are at particular risk for developing Pneumocystis carinii pneumonia (PCP), and prophylaxis against PCP is required for all patients receiving concomitant temozolomide 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, and 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 and monitored for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment. Temozolomide causes myelosuppression and patients may experience prolonged pancytopenia, which may result in aplastic anaemia, which in some cases has resulted in a fatal outcome.

Contraindications

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

PBS listing

APO-TEMOZOLOMIDE 180 mg capsules are listed on the PBS with 2 items, subject to restriction, at an ex-manufacturer price of A$99.70.

Regulatory history

APO-TEMOZOLOMIDE capsules in strengths of 5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg were first listed on the Australian Register of Therapeutic Goods on 19 February 2015 under licence category RE (sponsored by Arrotex Pharmaceuticals).