Warnings
WHEN Novantrone IS USED IN HIGH DOSES (> 14 mg/m2/d x 3 days) SUCH AS INDICATED FOR THE TREATMENT OF LEUKEMIA, SEVERE MYELOSUPPRESSION WILL OCCUR.  THEREFORE, IT IS RECOMMENDED THAT Novantrone BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN THE CHEMOTHERAPY OF THIS DISEASE.  LABORATORY AND SUPPORTIVE SERVICES MUST BE AVAILABLE FOR HEMATOLOGIC AND CHEMISTRY MONITORING AND ADJUNCTIVE THERAPIES, INCLUDING ANTIBIOTICS.  BLOOD AND BLOOD PRODUCTS MUST BE AVAILABLE TO SUPPORT PATIENTS DURING THE EXPECTED PERIOD OF MEDULLARY HYPOPLASIA AND SEVERE MYELOSUPPRESSION.  PARTICULAR CARE SHOULD BE GIVEN TO ASSURING FULL HEMATOLOGIC RECOVERY BEFORE UNDERTAKING CONSOLIDATION THERAPY (IF THIS TREATMENT IS USED) AND PATIENTS SHOULD BE MONITORED CLOSELY DURING THIS PHASE.  Novantrone ADMINISTERED AT ANY DOSE CAN CAUSE MYELOSUPPRESSION.

General

Patients with preexisting myelosuppression as the result of prior drug therapy should not receive Novantrone unless it is felt that the possible benefit from such treatment warrants the risk of further medullary suppression.

The safety of Novantrone (mitoxantrone for injection concentrate) in patients with hepatic insufficiency is not established (see CLINICAL PHARMACOLOGY).

Safety for use by routes other than intravenous administration has not been established.

Novantrone is not indicated for subcutaneous, intramuscular, or intra-arterial injection.  There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection.

Novantrone must not be given by intrathecal injection.  There have been reports of neuropathy and neurotoxicity, both central and peripheral, following intrathecal injection.  These reports have included seizures leading to coma and severe neurologic sequelae, and paralysis with bowel and bladder dysfunction.

Topoisomerase II inhibitors, including Novantrone, have been associated with the development of secondary acute myeloid leukemia and myelosuppression.

Cardiac Effects

Because of the possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin, the benefit-to-risk ratio of Novantrone therapy in such patients should be determined before starting therapy.

Functional cardiac changes including decreases in left ventricular ejection fraction (LVEF) and irreversible congestive heart failure can occur with Novantrone.  Cardiac toxicity may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease.  Such patients should have regular cardiac monitoring of LVEF from the initiation of therapy.  Cancer patients who received cumulative doses of 140 mg/m2 either alone or in combination with other chemotherapeutic agents had a cumulative 2.6% probability of clinical congestive heart failure.  In comparative oncology trials, the overall cumulative probability rate of moderate or severe decreases in LVEF at this dose was 13%.

Multiple Sclerosis

Changes in cardiac function may occur in patients with multiple sclerosis treated with Novantrone.  In one controlled trial (Study 1, see CLINICAL TRIALS, Multiple Sclerosis), two patients (2%) of 127 re