The information in this medication sheet has been adapted from the FDA-approved prescribing information for Novantrone.
Novantrone belongs to the general group of medicines called antineoplastics. Prior to its approval 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.
Note: Novantrone has not been approved for the treatment of primary-progressive MS (characterized by progression from disease onset with no acute attacks or remissions).
- The drug should be used only in those with normal cardiac function, once every three months at a dose of 12mg/m2. Periodic cardiac monitoring is required throughout the treatment period.
- 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.
Warnings and Precautions
- In response to post-marketing findings, the FDA has added a black box warning to the prescribing information for this medication:
- 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:
1. Current or prior history of heart disease
2. Simultaneous use of other medications that can damage the heart
3. previous therapy with certain kinds of chemotherapies (anthracyclines or anthracenediones)
- Secondary acute myelogenous leukemia (AML)
- 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 (.25%) developed AML. 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.
- 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
or if you have previously been treated with:
-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
- 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.