Home » Drug Information » FDA Approved Drugs » 2000
Medical Areas: Neurology | Family Medicine
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Novantrone (mitoxantrone hydrochloride)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved October 2000
Treatment Area: Reduction of neurologic disability and/or the frequency of clinical relapses in patients with multiple sclerosis
Novantrone has been approved for use in reducing neurologic
disability and/or the frequency of relapses in patients with
secondary (chronic) progressive, progressive relapsing, or
worsening relapsing-remitting multiple sclerosis (i.e., patients
whose neurologic status is significantly abnormal between
relapses). Novantrone is not indicated for the treatment of
patients with primary progressive multiple sclerosis.
White blood cells can produce the symptoms of multiple sclerosis
by attacking myelin, a fatty substance that surrounds nerve cells.
Novantrone suppresses the activity of T and B cells, and in this
manner slows the progression of the disease and reduces the
frequency of relapses.
Multiple sclerosis is diagnosed in over 350,000 people in the
United States. There is no one group of people who "get"
multiple sclerosis; however, trends show that it often strikes
between the ages of 30 and 50, and affects mostly women. Multiple
sclerosis is most commonly found in Canada, the United States,
South America, and Europe. (from the Multiple Sclerosis
The safety and effectiveness of Novantrone in multiple sclerosis
were assessed in two randomized, controlled multicenter trials. One
trial was conducted in subjects with secondary progressive or
progressive relapsing multiple sclerosis. Neurological disability
was evaluated based on the Kutzke Expanded Disability Status Scale
(EDSS). This scale ranges from 0.0 to 10.0, with increasing scores
indicating worsening condition. Subjects receive a placebo, 5 mg/m2
Novantrone, or 12 mg/m2 Novantrone administered intravenously every
three months for two years. At 24 months, the mean EDSS change
(month 24 value minus baseline) was 0.23 for the placebo group,
-0.23 for 5 mg/m2, and -0.13 for 12 mg/m2.
A second trial evaluated Novantrone in combination with
methylprednisolone (MP) and was conducted in subjects with
secondary progressive or worsening relapsing-remitting multiple
sclerosis who had residual neurological deficit between relapses. A
total of 42 subjects received monthly treatments of 1g of
intravenous MP alone or approximately 12 mg/m2 of intravenous
Novantrone plus 1 g of intravenous MP for six months. Subjects were
evaluated monthly, and study outcome was determined after six
months. The primary measure of effectiveness was a comparison of
the proportion of subjects in each treatment group who developed no
new Gd-enhancing MRI lesions at six months. Thirty-one percent of
subjects receiving MP alone were without new Gd-enhancing lesions
on MRIs, while 90% of subjects receiving Novantrone plus MP were
without lesions. (from Novantrone Package Insert)
Possible adverse events associated with Novantrone include (but
are not limited to) the following:
- Hair loss
- Hypotension (low blood pressure)
- Urinary tract infection
- Menstrual disorder
Mechanism of Action
Mitoxantrone, a DNA-reactive agent that intercalates into
deoxyribonucleic acid (DNA) through hydrogen bonding, causes
crosslinks and strand breaks. Mitoxantrone also interferes with
ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase
II, an enzyme responsible for uncoiling and repairing damaged DNA.
It has a cytocidal effect on both proliferating and
nonproliferating cultured human cells, suggesting lack of cell
cycle phase specificity.
Novantrone has been shown in vitro to inhibit B cell, T cell,
and macrophage proliferation and impair antigen presentation, as
well as the secretion of interferon gamma, TNFa, and IL-2.