Tecfidera Drug Interactions

Anti-neoplastic, immunosuppressive or corticosteroid therapies: Tecfidera has not been studied in combination with anti-neoplastic or immunosuppressive therapies and caution should, therefore, be used during concomitant administration. In multiple sclerosis clinical studies, the concomitant treatment of relapses with a short course of intravenous corticosteroids was not associated with a clinically relevant increase of infection.
Vaccines: Concomitant administration of non-live vaccines according to national vaccination schedules may be considered during Tecfidera therapy. In a clinical study involving a total of 71 patients with RRMS, patients on Tecfidera 240mg twice daily for at least 6 months (n=38) or non-pegylated interferon for at least 3 months (n=33), mounted a comparable immune response (defined as ≥2-fold increase from pre- to post-vaccination titre) to tetanus toxoid (recall antigen) and a conjugated meningococcal C polysaccharide vaccine (neoantigen), while the immune response to different serotypes of an unconjugated 23-valent pneumococcal polysaccharide vaccine (T-cell independent antigen) varied in both treatment groups. A positive immune response defined as a ≥4-fold increase in antibody titre to the three vaccines, was achieved by fewer subjects in both treatment groups. Small numerical differences in the response to tetanus toxoid and pneumococcal serotype 3 polysaccharide were noted in favour of non-pegylated interferon.
No clinical data are available on the efficacy and safety of live attenuated vaccines in patients taking Tecfidera. Live vaccines might carry an increased risk of clinical infection and should not be given to patients treated with Tecfidera unless, in exceptional cases, this potential risk is considered to be outweighed by the risk to the individual of not vaccinating.
Other fumaric acid derivatives: During treatment with Tecfidera, simultaneous use of other fumaric acid derivatives (topical or systemic) should be avoided.
In humans, dimethyl fumarate is extensively metabolised by esterases before it reaches the systemic circulation and further metabolism occurs through the tricarboxylic acid cycle, with no involvement of the cytochrome P450 (CYP) system. Potential interaction risks were not identified from in vitro CYP-inhibition and induction studies, a p-glycoprotein study, or studies of the protein binding of dimethyl fumarate and monomethyl fumarate (the primary metabolite of dimethyl fumarate).
Effects of other substances on dimethyl fumarate: Commonly used medicinal products in patients with multiple sclerosis, intramuscular interferon beta-1a and glatiramer acetate, were clinically tested for potential interactions with dimethyl fumarate and did not alter the pharmacokinetic profile of dimethyl fumarate.
Evidence from healthy volunteer studies suggests that Tecfidera-associated flushing is likely to be prostaglandin mediated. In two healthy volunteer studies, the administration of 325 mg (or equivalent) non-enteric coated acetylsalicylic acid, 30 minutes prior to Tecfidera, dosing over 4 days and over 4 weeks, respectively, did not alter the pharmacokinetic profile of Tecfidera. Potential risks associated with acetylsalicylic acid therapy should be considered prior to co-administration with Tecfidera in patients with RRMS. Long term (>4 weeks) continuous use of acetylsalicylic acid has not been studied (see Precautions and Adverse Reactions).
Concurrent therapy with nephrotoxic medicinal products (such as aminoglycosides, diuretics, non-steroidal anti-inflammatory drugs or lithium) may increase the potential of renal adverse reactions (e.g. proteinuria see Adverse Reactions) in patients taking Tecfidera (see Blood/laboratory tests under Precautions).
Consumption of moderate amounts of alcohol did not alter exposure to dimethyl fumarate and was not associated with an increase in adverse reactions. Consumption of large amounts of strong alcoholic drinks (more than 30% alcohol by volume) should be avoided within an hour of taking Tecfidera, as alcohol may lead to increased frequency of gastrointestinal adverse reactions.
Effects of dimethyl fumarate on other substances: In vitro CYP induction studies did not demonstrate an interaction between Tecfidera and oral contraceptives. In an in vivo study, co-administration of Tecfidera with a combined oral contraceptive (norgestimate and ethinyl estradiol) did not elicit any relevant change in oral contraceptive exposure. No interaction studies have been performed with oral contraceptives containing other progestogens, however an effect of Tecfidera on their exposure is not expected.
Paediatric population: Interaction studies have only been performed in adults.