ONKOTRONE

What it is

Onkotrone contains mitozantrone hydrochloride. Onkotrone is a clear, dark blue concentrated injection. Each mL of the solution for injection contains 2.328 mg mitozantrone hydrochloride (equivalent to 2 mg mitozantrone). Mitozantrone should be administered slowly as an intravenous infusion over a period of 15-30 minutes (not less than 5 minutes).

Approved indications Onkotrone is indicated for the treatment of:

— Locally advanced or metastatic carcinoma of the breast — Non-Hodgkin's lymphoma — Adult acute non-lymphocytic leukaemia (ANLL) — Chronic myelogenous leukaemia in blast crisis

Dosing overview

The recommended initial dosage for use as a single agent in breast cancer and lymphoma is 14 mg/m² of body surface area, given as a single intravenous dose, which may be repeated at 21-day intervals. A lower initial dose (12 mg/m² or less) is recommended in patients with inadequate bone marrow reserves due to prior therapy or poor general condition. For acute non-lymphocytic leukaemia, the recommended induction dose is 10 to 12 mg/m² mitozantrone for three days and 100 mg/m² of cytosine arabinoside for 7 days. If a second course is indicated, the mitozantrone is given for only 2 days and cytosine arabinoside for only 5 days. For single-agent dosage in acute non-lymphocytic leukaemia or chronic myelogenous leukaemia in blast crisis, the recommended dose for induction is 12 mg/m² of body surface area, given as a single intravenous dose daily for 5 consecutive days (total 60 mg/m²). Doses greater than 140 mg/m² are not recommended, particularly as a single bolus injection.

Key safety warnings

Doses greater than 140 mg/m² are not recommended, particularly as a single bolus injection, as such administrations have caused fatal overdose as a result of severe leucopenia and infection. Full blood counts must be checked before each administration of Onkotrone as well as undertaken serially during a course of treatment, and dosage adjustments may be necessary based on these counts. Following recommended doses of Onkotrone, leucopenia is usually transient, reaching the nadir at about 10 days after dosing, with recovery usually occurring by the twenty-first day, and white blood cell counts as low as 1.5 x 10⁹/L may be expected. Cases of functional cardiac changes, including congestive heart failure and decreases in left ventricular ejection fraction have been reported during Onkotrone therapy, most commonly in patients who have had prior treatment with anthracyclines, prior mediastinal radiotherapy or with pre-existing heart disease. It is recommended that cardiac monitoring be performed in patients without pre-existing cardiac risk factors before initiation of therapy and during therapy exceeding 140 mg/m² of mitozantrone. Topoisomerase II inhibitors, including mitozantrone, when used alone or concomitantly with other antineoplastic agents and/or radiotherapy, have been associated with the development of Acute Myeloid Leukaemia (AML), Acute Promyelocytic Leukaemia (APL) or Myelodysplastic Syndrome (MDS), and mitozantrone has been associated with the development of secondary AML in humans. Mitozantrone is excreted in human milk at significant concentrations (18 ng/mL) for 28 days after last administration, and because of the potential for serious adverse reactions in infants, breastfeeding should be discontinued before starting treatment.

Contraindications

Onkotrone is contraindicated in patients with known hypersensitivity to mitozantrone, in pregnancy and lactation, in patients with severe myelosuppression due to previous treatment with other cytotoxic agents or radiotherapy until bone marrow has recovered, in patients who have received prior substantial anthracycline therapy with abnormal cardiac function prior to initiation of therapy, in patients with severe hepatic impairment, and for intraarterial, subcutaneous, intramuscular or intrathecal administration due to associated toxicities.

Regulatory history

Onkotrone mitozantrone was first listed on the ARTG on 24 January 2001 in four strengths: 10 mg/5 mL, 20 mg/10 mL, 25 mg/12.5 mL, and 30 mg/15 mL.