TEMIZOLE

What it is

TEMIZOLE contains temozolomide as the active ingredient in capsule strengths of 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg. Temozolomide is an imidazotetrazine alkylating agent with anti-tumour activity that 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 a first-line treatment.

Dosing overview

Temozolomide capsules should be administered in the fasting state at least one hour before a meal. Capsules must not be opened or chewed but are to be swallowed whole with a glass of water.

Key safety warnings

Patients receiving concomitant temozolomide and radiotherapy are at particular risk for developing Pneumocystis carinii pneumonia (PCP), and prophylaxis against PCP is required for all patients receiving this combination 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. For patients on a 42-day treatment cycle, liver function tests should be repeated midway through this cycle, and for all patients, liver function tests should be checked after each treatment cycle. Hepatitis due to hepatitis B virus (HBV) reactivation has been reported, and 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 treated with temozolomide may experience prolonged pancytopenia that may result in aplastic anaemia, which in some cases has resulted in a fatal outcome. Prior to dosing, absolute neutrophil count must be greater than 1.5 × 10⁹/L and platelets greater than 100 × 10⁹/L. During cyclical treatment a complete blood count must be obtained on day 22 or within 48 hours of that day, and weekly until ANC is above 1.5 × 10⁹/L and platelet count exceeds 100 × 10⁹/L.

Contraindications

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

PBS listing

TEMIZOLE 5 mg capsules are listed on the PBS with restriction and an ex-manufacturer price of A$4.74. TEMIZOLE 20 mg capsules are listed on the PBS with restriction and an ex-manufacturer price of A$11.24. TEMIZOLE 250 mg capsules are listed on the PBS with restriction and an ex-manufacturer price of A$114.49.

Regulatory history

TEMIZOLE was first registered on the Australian Register of Therapeutic Goods (ARTG) on 19 July 2011 with six strength formulations: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg capsules.