Drug namesActive ingredientsBoxed warnings
TysabriNatalizumabWARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Cases of PML have been reported in patients taking TYSABRI who were recently or concomitantly treated with immunomodulators or immunosuppressants, as well as in patients receiving TYSABRI as monotherapy[see Warnings and Precautions (5.1)].
• Because of the risk of PML, TYSABRI is available only through a special restricted distribution program called the TOUCH® Prescribing Program. Under the TOUCH® Prescribing Program, only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse the product. In addition, TYSABRI must be administered only to patients who are enrolled in and meet all the conditions of the TOUCH® Prescribing Program [see Warnings and Precautions (5.1, 5.2)].
• Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium- enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [see Contraindications (4), Warnings and Precautions (5.1)].
Novantrone®MitoxantroneNOVANTRONE® (mitoxantrone for injection concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.
NOVANTRONE® should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration. (See ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions).
NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration. (See WARNINGS, General) Except for the treatment of acute nonlymphocytic leukemia, NOVANTRONE® therapy generally should not be given to patients with baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving NOVANTRONE®.
Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy with NOVANTRONE® or months to years after termination of therapy.
Cardiotoxicity risk increases with cumulative NOVANTRONE dose and may occur whether or not cardiac risk factors are present. Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or use of other cardiotoxic drugs may increase this risk. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk with NOVANTRONE, prescribers should consider the following: NOVANTRONE mitoXANTRONE for injection

All Patients:
All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to start of NOVANTRONE® therapy.
All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (ex. Echocardiogram, multi-gated radionuclide angiography (MUGA), MRI, etc.).
Multiple Sclerosis Patients:
MS patients with a baseline LVEF below the lower limit of normal should not be treated with NOVANTRONE®.
MS patients should be assessed for cardiac signs and symptoms by history, physical examination and ECG prior to each dose.
MS patients should undergo quantitative reevaluation of LVEF prior to each dose using the same methodology that was used to assess baseline LVEF. Additional doses of NOVANTRONE® should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF during NOVANTRONE® therapy.
MS patients should not receive a cumulative NOVANTRONE dose greater than 140 mg/m2.
-MS patients should undergo yearly quantitative LVEF evaluation after stopping NOVANTRONE to monitor for late occurring cardiotoxicity.
Secondary Leukemia: NOVANTRONE® therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia.
For additional information, see WARNINGS and DOSAGE AND ADMINISTRATION.

From: Appendix B, Black Box warnings for included drugs

Cover of Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis
Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet].
Smith B, Carson S, Fu R, et al.
Portland (OR): Oregon Health & Science University; 2010 Aug.
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.

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