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Generic Name: Dimethyl Fumarate
Class: Immunomodulatory Agents
VA Class: IM900
Chemical Name: Dimethyl (E)-but-2-enedioate
Molecular Formula: C6H8O4
CAS Number: 624-49-7


Fumaric acid derivative with immunomodulatory and disease-modifying activity in multiple sclerosis.1 7 8 9 10 11

Uses for Tecfidera

Multiple Sclerosis (MS)

Used in management of relapsing forms of MS (e.g., relapsing-remitting MS [RRMS]).1 2 3

Direct comparative studies between dimethyl fumarate and other oral drugs used in relapsing forms of MS (e.g., fingolimod, teriflunomide) have not been performed to date; however, clinical experience suggests that dimethyl fumarate may be more effective than teriflunomide and better tolerated than fingolimod.1 2 3 13

Slideshow: Multiple Sclerosis: What's New in Treatment Options?

Efficacy not established and not FDA-labeled for use in patients with primary-progressive MS.1 7 10

Tecfidera Dosage and Administration


  • Because of the risk of lymphopenia, obtain a CBC, including lymphocyte count, prior to initiation of therapy, following 6 months of therapy, every 6–12 months thereafter, and as clinically indicated.1 (See Lymphopenia under Cautions.)


Oral Administration

Administer orally twice daily with or without food.1 However, administration with food may reduce incidence of flushing and improve GI tolerability.1 10 21

Administration of non-enteric-coated aspirin (≤325 mg) 30 minutes prior to dimethyl fumarate may reduce the incidence and severity of flushing.1 14 (See Flushing under Cautions and also see Specific Drugs under Interactions.)

Swallow delayed-release capsules whole and intact.1 Do not crush or chew capsules; do not sprinkle the contents of the capsules on food.1



Multiple Sclerosis

Initially, 120 mg twice daily.1 After 7 days, increase to maintenance dosage of 240 mg twice daily.1

The Tecfidera 30-day Starter Pack, which contains 120-mg capsules for the first 7 days of therapy and 240-mg capsules for the next 23 days of therapy, is designed to be used during the first month of therapy.1

In patients who do not tolerate the usual maintenance dosage, consider a temporary dosage reduction from 240 mg twice daily to 120 mg twice daily.1 Resume recommended maintenance dosage of 240 mg twice daily within 4 weeks.1 Consider drug discontinuance in patients unable to tolerate a return to the usual maintenance dosage.1

Special Populations

Hepatic Impairment

No dosage adjustment necessary.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

No dosage adjustment necessary.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No dosage adjustment necessary.1 (See Geriatric Use under Cautions.)

Cautions for Tecfidera


  • Known hypersensitivity to dimethyl fumarate or any excipients in the formulation.1 (See Anaphylaxis and Angioedema under Cautions.)


Anaphylaxis and Angioedema

May cause anaphylaxis or angioedema after the first dose or at any time during therapy.1 Signs and symptoms of hypersensitivity reactions have included difficulty breathing, urticaria, and swelling of the throat and tongue.1 (See Contraindications under Cautions and also see Advice to Patients.)

Progressive Multifocal Leukoencephalopathy (PML)

An FDA alert in November 2014 described a fatal case of PML (an opportunistic infection of the brain caused by the JC virus that usually leads to death or severe disability) in a patient with MS treated with dimethyl fumarate for 4 years in a clinical trial.1 15 19 The patient had prolonged lymphopenia (i.e., lymphocyte counts predominantly <500/mm3 for 3.5 years) during dimethyl fumarate therapy;1 15 19 the causative role of lymphopenia in this case is not known.1 19 The patient had no other known medical conditions resulting in compromised immune system function, had not received natalizumab, and was not concurrently receiving any immunosuppressive or immunomodulatory drugs.1 15 19

Several cases of PML have been reported in Europe in patients receiving other preparations containing dimethyl fumarate.15 17 20

At the first sign or symptom suggestive of PML (see Advice to Patients), immediately withhold dimethyl fumarate therapy and perform an appropriate diagnostic evaluation.1 15

Monitor lymphocyte counts in patients receiving dimethyl fumarate.1 15 (See Lymphopenia under Cautions.)


May decrease lymphocyte counts.1 2 16 In placebo-controlled clinical trials, mean lymphocyte counts decreased by approximately 30% during the first year of therapy and remained stable thereafter.1 2 Mean lymphocyte counts improved 4 weeks following discontinuance of the drug, but did not return to baseline values.1 (See Actions.)

Although an increased incidence of serious infections was not observed in patients with decreased lymphocyte counts in controlled trials, one case of PML developed during an extension study in the setting of prolonged lymphopenia.1 (See Progressive Multifocal Leukoencephalopathy [PML] under Cautions.)

Not studied in patients with preexisting low lymphocyte counts.1

Obtain a CBC, including lymphocyte count, prior to initiation of dimethyl fumarate, following 6 months of therapy, every 6–12 months during therapy thereafter, and as clinically indicated.1

In patients with lymphocyte counts <500/mm3 persisting for >6 months, consider interruption of therapy.1 Consider monitoring lymphocyte counts until lymphopenia has resolved since lymphocyte recovery may be delayed following drug discontinuance.1

In patients with serious infections, consider withholding treatment until the infection has resolved.1 Consider patient's clinical circumstances when deciding whether to restart dimethyl fumarate therapy.1


May cause flushing (e.g., warmth, redness, itching, burning sensation).1 2 3 14 In clinical trials, 40% of dimethyl fumarate-treated patients experienced flushing.1 Symptoms generally are mild to moderate, begin soon after initiating therapy, and improve or resolve over time.1 3

Administration with food or pretreatment with non-enteric-coated aspirin may reduce incidence and/or severity of flushing.1 14 (See Administration under Dosage and Administration, see Specific Drugs under Interactions, and also see Actions.)

Specific Populations


Category C.1

Tecfidera pregnancy registry (for patients) at 866-810-1462 or .1


Not known whether dimethyl fumarate or its metabolites distribute into human milk.1 10 Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Flushing,1 2 3 14 abdominal pain,1 2 3 diarrhea,1 2 3 nausea.1 2 3 Incidence of flushing and adverse GI effects generally higher early in therapy (mainly in the first month) and decreases with continued therapy (see Administration under Dosage and Administration).1 2 10 21

Proteinuria, pruritus, reduced lymphocyte counts, increased aminotransferase concentrations (e.g., ALT, AST), transient eosinophilia (during the first 2 months of therapy).1 2 3

Interactions for Tecfidera

No potential drug interactions with dimethyl fumarate or its main active metabolite, MMF, identified in CYP inhibition and induction studies, P-glycoprotein studies, or studies of protein binding.1

Specific Drugs





Non-enteric-coated aspirin (325 mg given approximately 30 minutes before dimethyl fumarate over 4 days) did not alter MMF pharmacokinetics or incidence of adverse GI effects, but reduced incidence and severity of flushing1 14

Glatiramer acetate

Single dose of glatiramer acetate did not alter MMF pharmacokinetics1 10

Interferon beta

Single dose of interferon beta-1a did not alter MMF pharmacokinetics1 10

Oral contraceptives

Clinically important pharmacokinetic interactions unlikely10


Effectiveness of vaccines in patients receiving dimethyl fumarate not evaluated10

Tecfidera Pharmacokinetics


Following oral administration, dimethyl fumarate undergoes rapid presystemic hydrolysis by esterases and is converted to its active metabolite, monomethyl fumarate (MMF).1

Dimethyl fumarate is not quantifiable in plasma after oral administration; pharmacokinetic analyses were performed with plasma MMF concentrations.1


Median time to peak plasma MMF concentrations is 2–2.5 hours.1

Accumulation of MMF does not occur with multiple oral doses.1


High-fat, high-calorie meal did not affect AUC of MMF, but decreased peak plasma concentrations of MMF by 40% and delayed time to reach peak concentrations from 2 to 5.5 hours; incidence of flushing was decreased by approximately 25% in the fed state.1



Not known whether dimethyl fumarate or its metabolites distribute into human milk.1 10

Plasma Protein Binding

MMF is 27–45% protein bound; protein binding is independent of concentration.1



Extensively metabolized by esterases (present in GI tract, blood, and tissues) to MMF before reaching systemic circulation.1 MMF is further metabolized by the tricarboxylic acid (TCA) cycle; the CYP system is not involved in its metabolism.1 The major metabolites in plasma are MMF, fumaric acid, citric acid, and glucose.1

Elimination Route

Eliminated mainly (60%) by exhalation of carbon dioxide and to a minor extent by excretion in urine (16%) and feces (1%).1


MMF: Approximately 1 hour.1

Special Populations

Hepatic impairment: Pharmacokinetics not evaluated.1 However, hepatic impairment unlikely to affect exposure to MMF.1

Renal impairment: Pharmacokinetics not evaluated.1 However, renal impairment unlikely to affect exposure to MMF.1




Delayed-release Capsules

15–30°C; store in original container and protect from light.1 Once opened, discard bottles after 90 days.1


  • Exact mechanism of action in MS is unknown; however, immunomodulatory effect appears to be mediated by many cells of the immune system.1 7 9 11

  • Dimethyl fumarate and its active metabolite, MMF, activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans.1 7 11 The Nrf2 antioxidant response pathway is involved in the cellular response to oxidative stress.1 7 9 11

  • Nrf2-dependent upregulation of antioxidant response genes by dimethyl fumarate and MMF may protect various cells and tissues, including some from the CNS, from experimental toxic oxidative stress.7 10 11

  • Activation of the Nrf2 pathway by dimethyl fumarate and MMF also may inhibit proliferation of lymphocytes and hematopoietic stem cells.16 Subsets of peripheral blood leucocytes and lymphocytes appear to be affected differently, with a more pronounced reduction in CD8+ T-cell counts than in CD4+ T-cell counts observed in dimethyl fumarate-treated patients.16

  • MMF is a nicotinic acid receptor agonist in vitro.1 Nicotinic acid and fumaric acid derivatives such as dimethyl fumarate can cause skin flushing; flushing reactions may be mediated by activation of hydroxy-carboxylic acid receptor 2 (HCA2) and involve formation of prostaglandins.12 14

Advice to Patients

  • Importance of reading the manufacturer's patient information prior to beginning dimethyl fumarate therapy and rereading it each time the prescription is refilled.1

  • Risk of anaphylaxis and angioedema.1 Importance of advising patients to discontinue dimethyl fumarate and seek immediate medical care if they develop signs and symptoms of anaphylaxis or angioedema (e.g., difficulty breathing, urticaria, swelling of the throat and tongue).1

  • Importance of informing patients that PML has occurred in a dimethyl fumarate-treated patient, and is characterized by a progression of deficits and usually leads to death or severe disability over weeks to months.1 15 Importance of immediately informing clinician of any new or worsening symptoms suggestive of PML (e.g., progressive weakness on one side of the body; clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes) that have progressed over days to weeks.1 15 Importance of advising patients not to stop taking dimethyl fumarate without first consulting with their clinician.15

  • Importance of informing patients that they will receive 2 capsule strengths when starting treatment: 120-mg capsules for the 7-day initial dosage and 240-mg capsules for the maintenance dosage.1 Both strengths should be taken twice daily.1

  • Importance of informing patients to swallow dimethyl fumarate delayed-release capsules whole and intact, and not to crush, chew, or sprinkle the capsule contents on food.1 Importance of informing patients that the capsules may be taken with or without food.1

  • Importance of informing patients that flushing and adverse GI effects (e.g., abdominal pain, diarrhea, nausea) are common, particularly at the initiation of treatment, and that they may decrease over time.1 21 Importance of advising patients to contact their clinician if they experience persistent and/or severe flushing or GI reactions.1 Importance of also advising patients that taking dimethyl fumarate with food or taking non-enteric-coated aspirin prior to taking dimethyl fumarate may be helpful in such cases.1 21

  • Risk of decreased lymphocyte counts.1 Importance of periodic monitoring of CBCs.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 Importance of encouraging enrollment of pregnant women in the Tecfidera pregnancy registry at 866-810-1462 or on the website .1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., leukopenia, lymphopenia, infections).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dimethyl Fumarate


Dosage Forms


Brand Names



Capsules, delayed-release

120 mg



240 mg




7-day bottle containing 14 delayed-release capsules of dimethyl fumarate 120 mg (Tecfidera)

23-day bottle containing 46 delayed-release capsules of dimethyl fumarate 240 mg (Tecfidera)

Tecfidera 30-Day Starter Pack


AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions September 4, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


1. Biogen Inc. Tecfidera (dimethyl fumarate) delayed-release capsules prescribing information. Cambridge, MA; 2015 Apr.

2. Gold R, Kappos L, Arnold DL et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012; 367:1098-107. [PubMed 22992073]

3. Fox RJ, Miller DH, Phillips JT et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012; 367:1087-97. [PubMed 22992072]

4. Bar-Or A, Gold R, Kappos L et al. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study. J Neurol. 2013; 260:2297-305. [PubMed 23797999]

5. Hutchinson M, Fox RJ, Miller DH et al. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study. J Neurol. 2013; 260:2286-96. [PubMed 23749293]

6. Havrdova E, Hutchinson M, Kurukulasuriya NC et al. Oral BG-12 (dimethyl fumarate) for relapsing-remitting multiple sclerosis: a review of DEFINE and CONFIRM Evaluation of: Gold R, Kappos L, Arnold D, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012;367:1098-107; and Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012;367:1087-97. Expert Opin Pharmacother. 2013; 14:145-56. [PubMed 23971970]

7. Stangel M, Linker RA. Dimethyl fumarate (BG-12) for the treatment of multiple sclerosis. Expert Rev Clin Pharmacol. 2013; 6:355-62. [PubMed 23927662]

8. Albrecht P, Bouchachia I, Goebels N et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012; 9:163. [PubMed 22769044]

9. Lin SX, Lisi L, Dello Russo C et al. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro. 2011; 3:. [PubMed 21382015]

10. Biogen Idec Canada Inc. Tecfidera (dimethyl fumarate) delayed-release capsules 120 mg product monograph. Mississauga, Ontario; 2013 Mar 28.

11. Scannevin RH, Chollate S, Jung MY et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther. 2012; 341:274-84.

12. Hanson J, Gille A, Offermanns S. Role of HCA2 (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin. Pharmacol Ther. 2012; 136:1-7.

13. Anon. Dimethyl fumarate (Tecfidera) for multiple sclerosis. Med Lett Drugs Ther. 2013; 55:45-7.

14. Sheikh SI, Nestorov I, Russell H et al. Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther. 2013; 35:1582-94.

15. US Food and Drug Administration. FDA drug safety communication: FDA warns about case of rare brain infection PML with MS drug Tecfidera (dimethyl fumarate). Rockville, MD; 2014 Nov 25. From FDA website. Accessed 2015 Feb 23.

16. Spencer CM, Crabtree-Hartman EC, Lehmann-Horn K et al. Reduction of CD8+ T lymphocytes in multiple sclerosis patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm. 2015; 2:e76.

17. van Oosten BW, Killestein J, Barkhof F et al. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. New Engl J Med. 2013: 368:1658-9. [PubMed 23614604]

18. Miller DH, Fox RJ, Phillips JT et al. Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study. Neurology. 2015; 84:1145–52. [PubMed 25681448]

19. Rosenkranz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. New Engl J Med. 2015; 372:1476-8.

20. Nieuwkamp DJ, Murk JL, van Oosten BW et al. PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. New Engl J Med. 2015; 372:1474-6.

21. Phillips JT, Hutchinson M, Fox R et al. Managing flushing and gastrointestinal events associated with delayed-release dimethyl fumarate: experiences of an international panel. Mult Scler Relat Disord. 2014; 3:513-9. [PubMed 25877064]