Tecfidera Special Precautions

Blood/Laboratory Tests: Changes in renal and hepatic laboratory tests have been seen in clinical trials in subjects treated with Tecfidera (see Adverse Reactions). The clinical implications of these changes are unknown. Assessments of renal function (e.g. creatinine, blood urea nitrogen and urinalysis) and hepatic function (e.g. ALT and AST) are recommended prior to treatment initiation, after 3 and 6 months of treatment, every 6 to 12 months thereafter and as clinically indicated.
Prolonged Moderate to Severe Lymphopenia: Patients treated with Tecfidera may develop severe prolonged lymphopaenia (see Adverse Reactions). Tecfidera has not been studied in patients with pre-existing low lymphocyte counts and caution should be exercised when treating these patients. Prior to initiating treatment with Tecfidera, a current complete blood count including a lymphocyte must be performed. If lymphocyte count is found to be below the normal range, thorough assessment of possible causes should be completed prior to initiation of treatment with Tecfidera.
After starting therapy, complete blood counts including lymphocytes must be performed every 3 months. Consider interruption of Tecfidera in patients with lymphocyte count <0.5 x 10⁹/L persisting for more than 6 months, the benefit/risk balance of the therapy should be re-considered in discussion with the patient in the context of other therapeutic options available. Clinical factors and evaluation of any laboratory and imaging investigations could be included as part of this re-consideration. If treatment is continued despite a persistent lymphocyte count <0.5 x 10⁹/L, enhanced vigilance is recommended (see also subsection on PML).
Lymphocyte count should be followed until recovery. Upon recovery and in the absence of alternative treatment options, decisions about whether or not to restart Tecfidera after treatment discontinuation should be based on clinical judgement.
MR Imaging: Before initiating treatment with Tecfidera, a baseline MRI should be available (usually within 3 months) as a reference. The need for further MRI scanning should be considered in accordance with national and local recommendations. MRI imaging may be considered as part of increased vigilance in patients considered at increased risk of PML. In case of clinical suspicion of PML, MRI should be performed immediately for diagnostic purposes.
Progressive Multifocal Leukoencephalopathy (PML): PML cases have occurred with Tecfidera and other products containing fumarates in the setting of severe and prolonged lymphopenia. PML is an opportunistic infection caused by John-Cunningham virus (JCV), which may be fatal or result in severe disability. PML can only occur in the presence of a JCV infection. If JCV testing is undertaken, it should be considered that the influence of lymphopenia on the accuracy of anti-JCV antibody test has not been studied in Tecfidera treated patients. It should also be noted that a negative anti JCV antibody test (in the presence of normal lymphocyte counts) does not preclude the possibility of subsequent JCV infection.
Prior Treatment with Immunosuppressive or Immunomodulating Therapies: No studies have been performed evaluating the efficacy and safety of Tecfidera when switching patients from other disease-modifying therapies to Tecfidera. The contribution of prior immunosuppressive therapy to the development of PML in patients treated with Tecfidera is unknown. When switching patients from other disease-modifying therapy to Tecfidera, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time reducing the risk of reactivation of MS.
A complete blood count is recommended prior to initiating Tecfidera and regularly during treatment (see Blood/Laboratory Tests previously mentioned).
Tecfidera can generally be started immediately after discontinuation of interferon or glatiramer acetate.
Severe Renal and Hepatic Impairment: Tecfidera has not been studied in patients with severe renal or severe hepatic impairment and caution should, therefore, be used in these patients (see Dosage & Administration).
Severe Active Gastrointestinal Disease: Tecfidera has not been studied in patients with severe active gastrointestinal disease and caution should, therefore, be used in these patients.
Flushing: In clinical trials, 34% of Tecfidera treated patients experienced flushing. In the majority of patients who experienced flushing, it was mild or moderate in severity.
In clinical trials, 3 patients out of a total of 2,560 patients treated with Tecfidera experienced serious flushing symptoms that were probable hypersensitivity or anaphylactoid reactions. These events were not life-threatening, but led to hospitalisation. Prescribers and patients should be alert to this possibility in the event of severe flushing reactions (see Dosage & Administration, Adverse Reactions and Interactions).
Infections: In phase III placebo-controlled studies, the incidence of infections (60% vs 58%) and serious infections (2% vs 2%) was similar in patients treated with Tecfidera or placebo, respectively. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8 x 10⁹/L or <0.5 x 10⁹/L. During treatment with Tecfidera in the MS placebo controlled trials, mean lymphocyte counts decreased by approximately 30% from baseline at one year and then plateaued (see Adverse Reactions). Mean lymphocyte counts remained within normal limits. Patients with lymphocyte counts <0.5 x 10⁹/L were observed in <1% of patients treated with placebo and 6% of patients treated with Tecfidera. In clinical studies (both controlled and uncontrolled), 2% of patients experienced lymphocyte counts <0.5 x 10⁹/L for at least six months. In these patients, the majority of lymphocyte counts remained <0.5 x 10⁹/L with continued therapy.
If therapy is continued in the presence of prolonged moderate to severe lymphopenia , the risk of an opportunistic infection, including Progressive Multifocal Leukoencephalopathy (PML) cannot be ruled out (refer to previous subsection PML for further details).
If a patient develops a serious infection, suspending treatment with Tecfidera should be considered and the benefits and risks should be reassessed prior to re-initiation of therapy. Patients receiving Tecfidera should be instructed to report symptoms of infections to a physician. Patients with serious infections should not start treatment with Tecfidera until the infection(s) is resolved.
Effects on Ability to Drive and Use Machines: No studies on the ability to drive and use machines have been conducted.