s observed. Neutropenic fever/infection occurred in 11% and 10% of patients receiving NOVANTRONE + corticosteroids, respectively, on the two trials. Platelets < 50,000/mm3 were noted in 4% and 3% of patients receiving NOVANTRONE + corticosteroids on these trials, and there was one patient death on NOVANTRONE + hydrocortisone due to intracranial hemorrhage after a fall.
Gastrointestinal
Nausea and vomiting occurred acutely in most patients and may have contributed to reports of dehydration, but were generally mild to moderate and could be controlled through the use of antiemetics. Stomatitis/mucositis occurred within 1 week of therapy.
Cardiovascular
Congestive heart failure, tachycardia, EKG changes including arrhythmias, chest pain, and asymptomatic decreases in left ventricular ejection fraction have occurred. (See WARNINGS)
Pulmonary
Interstitial pneumonitis has been reported in cancer patients receiving combination chemotherapy that included NOVANTRONE.
OVERDOSAGE
There is no known specific antidote for NOVANTRONE. Accidental overdoses have been reported. Four patients receiving 140-180 mg/m2 as a single bolus injection died as a result of severe leukopenia with infection. Hematologic support and antimicrobial therapy may be required during prolonged periods of severe myelosuppression.
Although patients with severe renal failure have not been studied, NOVANTRONE is extensively tissue bound and it is unlikely that the therapeutic effect or toxicity would be mitigated by peritoneal or hemodialysis.
DOSAGE AND ADMINISTRATION
(See also WARNINGS)
Multiple Sclerosis
The recommended dosage of NOVANTRONE is 12 mg/m2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months. Left ventricular ejection fraction (LVEF) should be eva luated by echocardiogram or MUGA prior to administration of the initial dose of NOVANTRONE and all subsequent doses. In addition, LVEF eva luations are recommended if signs or symptoms of congestive heart failure develop at any time during treatment with NOVANTRONE NOVANTRONE should not be administered to multiple sclerosis patients with an LVEF <50%, with a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of ≥ 140 mg/m2. Complete blood counts, including platelets, should be monitored prior to each course of NOVANTRONE and in the event that signs or symptoms of infection develop. NOVANTRONE generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm3. Liver function tests should also be monitored prior to each course. NOVANTRONE therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because NOVANTRONE clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.
Women with multiple sclerosis who are biologically capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, and the results should be known, before receiving each dose of NOVANTRONE (see WARNINGS, Pregnancy).
Hormone-Refractory Prostate Cancer
Based on data from two Phase 3 comparative trials of NOVANTRONE plus corticosteroids versus corticosteroids alone, the recommended dosage of NOVANTRONE is 12 to 14 mg/m2 given as a short intravenous i |
