- Should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents
Intravenous Use Only
- Should be given slowly into a freely flowing intravenous infusion. It must never be given IM, SC, or intra-arterially.
- Not for Intrathecal Use: Severe injury with permanent sequelae can result from intrathecal administration.
- Severe local tissue damage can occur if there is extravasation during administration.
Baseline Neutrophil Count
- Except for the treatment of acute nonlymphocytic leukemia, mitoxantrone therapy should not be given to patients with baseline neutrophil counts < 1>3.
- In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed in all patients receiving this drug.
- CHF, potentially fatal may occur either during therapy with this drug or moths to years after termination of therapy.
- Cardiotoxicity risk increases with cumulative dose and may occur whether or not cardiac risk factors are present.
- Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or the use of other cardiotoxic drugs may increase the risk.
- In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk with this agent, prescribers should consider the following:
- All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to the start of therapy.
- All patients should have baseline evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology [e.g. echocardiogram, multi-gated radionuclide angiography (MUGA)].
Multiple Sclerosis Patients:
- Mulitple sclerosis (MS) patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone.
- MS patients should be assessed for cardiac signs and symptoms by history, physical examination and ECG prior to each dose.
- MS patients should undergo quantitative reevaluation of LVEF prior to each dose using the same methodology that was used to assess baseline LVEF. Additional doses of mitoxantrone should not be administered to MS patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF suring mitoxantrone therapy.
- Patients with MS should not receive a cumulative dose greater than 140 mg/m2.
- MS patients should undergo yearly quantitative LVEF evaluation after stopping mitoxantrone to monitor for late occuring cardiotoxicity.
Secondary Acute Myelogenous Leukemia (AML)
- Mitoxantrone therapy in patients with MS and in patients with cancer increases the risk of developing secondary AML.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Perform frequent peripheral blood cell counts during therapy
- Monitor for cardiac toxicity and disease prior to initiation of therapy.
- Evaluate LVEF prior to initial dose.
- In cancer patients: CHF risk estimated at 2.6% up to cumulative dose of 140 mg/m2.
- Cumulative risk of drug related AML when this drug was used in combiantion with other cytotoxic agents and radiotherapy was estimated at 1.1% and 1.6% at 5 and 10 yrs, respectively.
FDA and Industry Communications
Updated January 2018