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Novantrone®
(mitoxantrone)
Novantrone belongs to the general group
of medicines called antineoplastics. Prior to its approval
in the United States for use in MS, it was used only to treat
certain forms of cancer. It acts in MS by suppressing the
activity of T cells, B cells, and macrophages that are thought
to lead the attack on the myelin sheath.
The use of Novantrone for the treatment of MS has been evaluated
in a series of European studies over a period of ten years. In
a randomized, placebo-controlled, multi-center clinical trial
involving patients with secondary-progressive or progressive-relapsing
disease, participants received 12mg/m2 of Novantrone by short
IV infusion once every three months for 24 months. Novantrone
was found to delay the time to first treated relapse and time
to disability progression. It also reduced the number of treated
relapses and number of new lesions detected by magnetic resonance
imaging.
Approval by the U.S. Food and Drug Administration
(FDA)
Based on findings from these studies, the FDA approved
Novantrone in for reducing neurologic disability and/or the
frequency of clinical relapses (attacks) in:
- Patients with secondary
progressive MS (disease that has changed from relapsing-remitting
to progressive at a variable rate)
- Progressive-relapsing
MS (disease characterized by gradual increase in disability
from onset with clear, acute relapses along the way);
- Worsening relapsing-remitting
MS (disease characterized by clinical attacks without complete
remission, resulting in a step-wise worsening of disability.
Novantrone has not been approved for
the treatment of primary-progressive MS (characterized by
progression from disease onset with no acute attacks or remissions).
Usage in Canada
Health Canada has not specifically approved
Novantrone for use in multiple sclerosis, but it can be used
at the discretion of a physician for people with worsening relapsing-remitting
or secondary-progressive MS. This is known as “off label”
use.
Proper Usage
The drug should be used only in those with normal cardiac
function, once every three months at a dose of 12mg/m2.
The lifetime cumulative dose is limited to 140 mg/m2 (approximately
8-12 doses over two to three years) because of possible cardiac
toxicity.
Because Novantrone can increase the risk for infection by
decreasing the number of protective white blood cells, blood
counts and liver function should be evaluated prior to each
dose.
Note:
In response to post-marketing findings, the FDA has added
a black box warning to the prescribing information for Novantrone:
- Prior to the start
of treatment, a person should be carefully evaluated (by
examination and medical history) for signs and symptoms
of heart disease.
- A baseline evaluation
of left ventricular ejection fraction (LVEF) should be performed.
- A person whose LVEF
is lower than 50% should not be given Novantrone.
- LVEF should be re-tested
prior to each dose of Novantrone.
- Any person whose
LVEF changes significantly or drops below 50% should have
no further Novantrone treatments.
The factors that are known to increase
a person's risk for cardiotoxicity with Novantrone are:
- a current or prior history
of heart disease;
- the simultaneous use of
other medications that can damage the heart;
- previous therapy with
certain kinds of chemotherapies (anthracyclines or anthracenediones).
In post-marketing data collection, secondary
acute myelogenous leukemia (AML)-a type of cancer-has been
reported in MS patients and cancer patients treated with
Novantrone. In one group of MS patients treated with Novantrone,
two out of 802 patients developed AML. This represents an elevated
risk of .25%. The risk of leukemia following treatment with
Novantrone is increased for patients who have been treated
with other types of chemotherapies called anthracyclines.
Because post-marketing data collection is not controlled in
any way, it is not possible to determine the exact risk for
a person with MS of developing AML following treatment with
Novantrone. The Registry to Evaluate NOVANTRONE® Effects
in Worsening MS (RENEW) was established in 2001 to follow
a group of 505 MS patients who had been treated with Novantrone.
This observational study is scheduled to last five years.
Precautions
It is important that your
doctor check your progress at regular intervals to make sure
that this medicine is working properly and to check for unwanted
effects.
While being treated with this medication,
and during the period following treatment, do not have any immunizations
(vaccinations) with live virus vaccines without your doctor's
approval. Mitoxantrone may lower your body's resistance to infection,
making you susceptible to the infection that the immunization
is designed to help you avoid. Neither you nor anyone in your
household should take the oral polio vaccine.
If possible, avoid people with infections. Contact your physician
if you think you are getting an infection, or if you get a fever
or chills, cough or hoarseness, lower back or side pain, or painful
or difficult urination.
When receiving Novantrone, it is important for your
physician to know if you are taking any of the following:
- Amphotericin B by injection
- Antithyroid agents
- Azathioprine
- Chloramphenicol
- Colchicine
- Flucytosine
- Ganciclovir
- Plicamycin
- Probenecid
- Sulfinpyrazone
- Zidovudine
or if you have previously been treated with:
- radiation
- other cancer medications
The presence of other medical problems
may affect the use of Novantrone. Let your doctor know if
you have any of the following:
- chicken pox or recent
exposure to it
- herpes zoster (shingles)
- gout or history of gout
or kidney stones
- heart disease
- liver disease
The fluid for infusion is dark blue and may cause your urine
to become blue-green in color for a period of 24 hours after
each administration. The whites of the eyes may also appear
bluish in color.
Tell your doctor if you are
pregnant or intending to have children. This medicine may cause
birth defects if either the man or woman is receiving it at
the time of conception. A pregnancy test is recommended prior
to each treatment for women of child-bearing age. Many medications
of this type can cause permanent sterility. Be sure you have
discussed this with your physician before taking this medication.
Novantrone
is excreted in human milk. Breast-feeding should be discontinued
before a woman starts treatment.
A higher incidence of leukemia
has been reported in cancer patients, previously treated with
chemotherapy, who were then treated with higher doses of Novantrone
than is prescribed for treating MS.
Possible Side Effects
Side effects that may go away as your body adjusts to the
medication and do not require medical attention unless they
continue or are bothersome: nausea, temporary hair loss, and
menstrual disorders in females.
Side effects that should be reported to your physician as
soon as possible: fever or chills, lower back or side pain;
painful or difficult urination; swelling of feet and lower
legs; black, tarry stools, cough or shortness of breath; sores
in mouth and on lips, stomach pain.
Reprinted with permission from Rosalind C. Kalb (ed.),
Multiple Sclerosis: The Questions You Have—The Answers
You Need, 3rd Edition. New York: Demos Medical Publishing,
Inc., 2004
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