Changes Made to Tecfidera’s Label
The United States Food and Drug Administration (FDA) recently made some changes to the product labeling for Tecfidera® (dimethyl fumarate). These changes instruct physicians on how to best prescribe the drug for their patients to minimize the potential for certain side effects and adverse events. The revisions are described below; please note that several of the definitions given are from MedlinePlus (from the National Institutes of Health).
Section 2.1, DOSAGE AND ADMINISTRATION, Dosing Information
As noted on the original label, “The starting dose for Tecfidera is 120 mg twice a day orally. After seven days, the dose should be increased to the maintenance dose of 240 mg twice a day orally.”
The revised drug labeling has added, “Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose. Within four weeks, the recommended dose of 240 mg twice a day should be resumed. Discontinuation of Tecfidera should be considered for patients unable to tolerate return to the maintenance dose.”
This same section also talks about the potential side effect of flushing, which is a sudden reddening of the face, neck, or upper chest, as well as the feeling of uncomfortable itching or heat. As noted in the original label, “The incidence of flushing may be reduced by administration of Tecfidera with food.”
The revised drug labeling has added another strategy to reduce the potential for flushing. “Alternatively, administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to Tecfidera dosing may reduce the incidence or severity of flushing.”
Section 4, CONTRAINDICATIONS
These are specific situations in which a drug, procedure, or surgery should not be used because it may be harmful to the patient. Previously the label listed no contraindications, but it now states, “Tecfidera is contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients [inactive ingredients used to make the drug] of Tecfidera. Reactions have included anaphylaxis and angioedema.” Anaphylaxis is an allergic reaction, and while it can include redness, as seen with flushing, it also can include a range of symptoms – some very serious – such as hives, itching, swelling, breathing problems, and more. Angioedema is swelling that is similar to hives, but the swelling is under the skin instead of on the surface.
Section 5.1, WARNINGS AND PRECAUTIONS, Anaphylaxis and Angioedema
Although rare, physicians and patients need to watch for these types of serious allergic reactions. The new information states, “Tecfidera can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms have included difficulty breathing, urticaria [hives], and swelling of the throat and tongue. Patients should be instructed to discontinue Tecfidera and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema.”
Section 5.2, WARNINGS AND PRECAUTIONS, Progressive Multifocal Leukoencephalopathy (PML)
PML is a potentially fatal condition that occurred in one patient taking Tecfidera. The new label information explains that a fatal case of PML occurred in a patient with MS who received Tecfidera for four years while enrolled in a clinical trial. The label explains, “PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. During the clinical trial, the patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years) while taking Tecfidera..." Lymphopenia is a reduction in circulating lymphocytes, which are white blood cells aimed at fighting disease and infection. According to the FDA, "The role of lymphopenia in this case is unknown."
Section 5.3, WARNINGS AND PRECAUTIONS, Lymphopenia
New information has been added to the section on lymphopenia. In general, the section explains that “Tecfidera may decrease lymphocyte counts. In the MS placebo controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with Tecfidera and then remained stable.” The section goes on to state that 6% of patients taking Tecfidera in the clinical trials experienced lymphocyte counts of less than 0.5×109/L, which is below the lower limit considered normal (0.91×109/L).
In these trials, 2% of patients experienced these low lymphocyte counts (less than 0.5 x 109/L) for at least six months. The revised labeling includes these instructions: “Before initiating treatment with Tecfidera, a CBC [complete blood count] including lymphocyte count should be obtained. A CBC including lymphocyte count should also be obtained after six months of treatment, every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of Tecfidera in patients with lymphocyte counts <0.5 x 109/L persisting for more than six months. Given the potential for delay in lymphocyte recovery after discontinuation of Tecfidera, consider following lymphocyte counts until lymphopenia is resolved. Withholding treatment should be considered in patients with serious infections until the infection(s) is resolved. Decisions about whether or not to restart Tecfidera should be individualized based on clinical circumstances.”
Please note that this article only provides highlights of the labeling changes for Tecfidera. For full drug and prescribing information, please visit Tecfidera’s website at www.tecfidera.com.
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Written by Susan Wells Courtney
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer