Dimethyl Fumarate
Quick Facts
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Relapsing forms of multiple sclerosis — including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease | Adults (≥18 years) | Monotherapy | FDA Approved |
| Moderate-to-severe plaque psoriasis (Skilarence formulation) | Adults requiring systemic therapy | Monotherapy | EU Approved · Off-label US |
Dimethyl fumarate is a fumaric acid ester originally used for decades in Germany as part of a combination product (Fumaderm) for plaque psoriasis. The delayed-release oral capsule (Tecfidera) was approved by the FDA in 2013 for relapsing forms of multiple sclerosis on the basis of the Phase III DEFINE and CONFIRM trials, both published in the New England Journal of Medicine in 2012. In 2017, a single-agent oral tablet formulation of dimethyl fumarate (Skilarence) was approved in the European Union for moderate-to-severe plaque psoriasis; this product is not available in the United States.
Dimethyl fumarate sits within the AAN treatment hierarchy as one of several oral disease-modifying therapies for relapsing MS, alongside teriflunomide, fingolimod and other sphingosine-1-phosphate receptor modulators, and the more recently approved diroximel fumarate (Vumerity, a prodrug) and monomethyl fumarate (Bafiertam, the active metabolite given directly). Across these fumarate products the underlying pharmacology is shared; the differences lie chiefly in gastrointestinal tolerability (diroximel) and pill burden (monomethyl fumarate).
Plaque psoriasis (US): Some specialists use dimethyl fumarate off-label for moderate-to-severe psoriasis based on its EU approval and decades of European experience. Evidence: moderate quality (randomized trials with Skilarence and historical Fumaderm data).
Other uses are limited. Despite its broad anti-inflammatory and antioxidant pharmacology, dimethyl fumarate is not established for other neurological or dermatological diseases outside the indications above and should not be substituted for therapies with disease-specific evidence.
Dosing
Dimethyl fumarate has a fixed dosing schedule independent of body weight, age, and renal or hepatic function. The 7-day starter pack is designed to improve gastrointestinal and flushing tolerability during initiation; most adverse reactions emerge in month 1 and ease over time. Capsules must be swallowed whole — they are delayed-release and the enteric coating cannot be disrupted.
Standard Dosing — Adults
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Relapsing MS — initiation (days 1–7) | 120 mg PO BID | — | — | Take with or without food; food may reduce flushing Swallow whole; do not crush, chew, or sprinkle on food |
| Relapsing MS — maintenance (day 8 onward) | — | 240 mg PO BID | 240 mg PO BID (= 480 mg/day) | No benefit shown for higher doses (TID was studied and showed no advantage over BID) |
| Tolerability issue during maintenance | — | Temporarily reduce to 120 mg PO BID | Resume 240 mg BID within 4 weeks | Discontinue if patient cannot tolerate return to maintenance dose Most flushing and GI events emerge in month 1 and improve with continued therapy |
| Flushing prophylaxis (optional) | — | Non-enteric-coated aspirin up to 325 mg 30 minutes before each dose | — | Aspirin does not alter MMF pharmacokinetics; weigh routine aspirin use against bleeding risk Taking with food provides similar flushing reduction (~25% in the fed state) |
Special Populations
| Population | Recommendation | Rationale |
|---|---|---|
| Renal impairment (any severity) | No dose adjustment required | Renal elimination accounts for only ~16% of the dose; not formally studied but adjustment is not expected to be needed |
| Hepatic impairment (any severity) | No dose adjustment required | Not formally studied; predominant elimination is via CO2 exhalation and no CYP metabolism is involved |
| Body weight, age, sex, race | No dose adjustment required | Population PK analyses found no clinically relevant effect on MMF exposure |
| Geriatric patients (≥65 years) | No specific adjustment; clinical experience limited | Pivotal trials enrolled few patients ≥65 years |
| Pediatric patients (<18 years) | Not recommended | Safety and effectiveness not established |
| Pre-existing low lymphocyte count | Not studied; obtain baseline CBC and weigh risk individually | Lymphopenia is a known adverse effect; pre-existing low ALC is a relative contraindication in clinical practice |
Approximately 40% of patients experience flushing on dimethyl fumarate, and around 18% report abdominal pain. Both classes of reactions emerge primarily in the first month, are usually mild to moderate, and improve with continued therapy. The 7-day 120 mg BID starter dose, taking the medication with food, and using non-enteric-coated aspirin 30 minutes before dosing are the three evidence-based interventions that allow most patients to reach and stay on the 240 mg BID maintenance dose. Discontinuation rates for flushing (~3%) and GI events (~4%) in the placebo-controlled trials remain modest when these strategies are applied.
Pharmacology
Mechanism of Action
The mechanism by which dimethyl fumarate exerts its therapeutic effect in multiple sclerosis is not fully established. Both dimethyl fumarate and its active metabolite monomethyl fumarate (MMF) activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is involved in the cellular response to oxidative stress and induces a battery of cytoprotective and anti-inflammatory gene products. MMF also acts as an agonist at the hydroxycarboxylic acid receptor 2 (HCA2, also known as the nicotinic acid receptor or GPR109A) in vitro; this activity is thought to contribute to flushing and may contribute to anti-inflammatory effects on macrophages and dendritic cells.
Clinically, dimethyl fumarate produces a modest dose-related decrease in absolute lymphocyte count, with selective reductions in CD8+ T cells more pronounced than reductions in CD4+ T cells in many patients. This shift in lymphocyte subsets, together with effects on immune-cell trafficking and oxidative defence, is believed to underlie its therapeutic activity in relapsing MS — but it is also the basis for the risk of severe lymphopenia and progressive multifocal leukoencephalopathy (PML) that accompanies long-term therapy.
ADME Profile
Because dimethyl fumarate undergoes rapid presystemic hydrolysis by ubiquitous esterases in the gut, blood, and tissues, parent drug is not quantifiable in plasma after oral administration. All pharmacokinetic parameters refer to the active metabolite monomethyl fumarate (MMF).
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Rapid presystemic ester hydrolysis to MMF; Tmax 2–2.5 h. Mean steady-state Cmax 1.87 mg/L and AUC 8.21 mg·h/L on 240 mg BID with food. Cmax and AUC increase approximately dose-proportionally over 120–360 mg | A high-fat, high-calorie meal does not change AUC but reduces Cmax by ~40% and delays Tmax to ~5.5 h, with ~25% lower flushing incidence — a useful tolerability strategy |
| Distribution | Apparent Vd of MMF 53–73 L; plasma protein binding 27–45% and concentration-independent | Low-to-moderate protein binding makes displacement interactions clinically unimportant |
| Metabolism | Esterase-mediated conversion of dimethyl fumarate to MMF; further breakdown of MMF through the tricarboxylic acid (TCA) cycle to fumaric acid, citric acid, and glucose; no CYP P450 involvement | No clinically significant CYP-mediated drug interactions; no dose adjustments for CYP inducers or inhibitors |
| Elimination | ~60% of an administered dose is eliminated as exhaled CO2; ~16% renal and ~1% fecal. Mean terminal t½ of MMF ~1 hour. No accumulation with multiple BID dosing | Short half-life means BID dosing is required; the lack of accumulation simplifies titration and limits residual exposure after discontinuation |
Dimethyl fumarate is not a substrate, inhibitor, or inducer of P-glycoprotein in vitro at clinically relevant concentrations, and no interaction has been demonstrated with single doses of interferon beta-1a, glatiramer acetate, or with combined oral contraceptives (norelgestromin/ethinyl estradiol). Therapeutic drug monitoring is not used.
Side Effects
Adverse-event data below are drawn from the integrated safety analysis of the two placebo-controlled Phase III studies (DEFINE and CONFIRM), in which 769 patients received dimethyl fumarate 240 mg twice daily and 771 received placebo. Frequencies shown are the dimethyl fumarate rate followed by the placebo rate. Only events that occurred at ≥2% higher incidence than placebo are listed in the PI’s primary table.
| Adverse Effect | Incidence (DMF vs Placebo) | Clinical Note |
|---|---|---|
| Flushing (warmth, redness, pruritus, burning) | 40% vs 6% | Most common adverse reaction; emerges soon after initiation, usually mild–moderate, improves over time. ~3% discontinue; <1% have severe flushing requiring hospitalization |
| Abdominal pain | 18% vs 10% | Part of the GI symptom cluster that peaks in month 1 |
| Diarrhea | 14% vs 11% | Modest absolute increase over placebo |
| Nausea | 12% vs 9% | Taking with food may help |
| Adverse Effect | Incidence (DMF vs Placebo) | Clinical Note |
|---|---|---|
| Vomiting | 9% vs 5% | Usually transient |
| Pruritus | 8% vs 4% | May occur with or independent of flushing |
| Rash | 8% vs 3% | Most are mild; evaluate any new rash for hypersensitivity |
| Albumin in urine | 6% vs 4% | Usually transient and clinically silent; persistent proteinuria warrants further workup |
| Erythema | 5% vs 1% | Often part of the flushing complex |
| Dyspepsia | 5% vs 3% | Component of the early GI symptom cluster |
| Aspartate aminotransferase (AST) increased | 4% vs 2% | Most elevations are <3× ULN and occur in the first 6 months |
| Lymphopenia (laboratory) | 2% vs <1% | Refers to the lymphopenia adverse-event term; the proportion with lymphocyte counts <0.5 × 109/L during therapy is approximately 6% |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis and angioedema | Postmarketing — frequency not established | After first dose or any time during therapy | Discontinue and do not restart; treat as for any anaphylactic reaction; seek emergency care |
| Progressive multifocal leukoencephalopathy (PML) | Rare (postmarketing); has occurred predominantly in patients with prolonged lymphopenia, but reported with lymphocyte counts <0.9 × 109/L | Months to years | Withhold at first sign or symptom suggestive of PML (progressive hemiparesis, visual disturbance, cognitive or personality change); obtain MRI and CSF JCV PCR |
| Severe persistent lymphopenia | ~6% of treated patients had ALC <0.5 × 109/L; ~2% had prolonged severe lymphopenia for ≥6 months | First year of treatment | Consider interruption if ALC persistently <0.5 × 109/L for >6 months; recovery can take many months |
| Herpes zoster, including disseminated zoster, zoster ophthalmicus, and CNS zoster | Postmarketing — frequency not established | Any time during therapy | Treat zoster promptly; consider withholding dimethyl fumarate until infection resolves |
| Other serious opportunistic infections (HSV, CMV, West Nile virus, Candida, Aspergillus, Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) | Postmarketing — frequency not established; reported with both reduced and normal ALC | Variable | Prompt diagnostic evaluation and pathogen-directed treatment; consider withholding dimethyl fumarate |
| Liver injury (clinically significant) | Postmarketing; transaminase elevations >5× ULN with bilirubin >2× ULN reported, none progressing to liver failure or death in published cases | Days to several months | Discontinue if clinically significant liver injury suspected; check ALT, AST, ALP, total bilirubin at baseline and as clinically indicated |
| Serious gastrointestinal reactions (perforation, ulceration, hemorrhage, obstruction) — Warning added 12/2023 | Postmarketing reports across fumaric acid esters, some fatal; in clinical trials serious GI events occurred in 1% (vomiting 0.3%, abdominal pain 0.3%, none fatal) | Majority within 6 months of fumarate initiation | Promptly evaluate new or worsening severe abdominal pain, hematemesis, melena, or rectal bleeding; discontinue dimethyl fumarate |
| Acute pancreatitis | Postmarketing — frequency not established | Variable | Discontinue and evaluate any patient with new severe upper abdominal pain |
| Persistent transaminase elevation ≥3× ULN with bilirubin >2× ULN (Hy’s law pattern) | Postmarketing | Variable | Discontinue; investigate for drug-induced liver injury |
| Alopecia | Postmarketing — usually mild and reversible | Months | Reassure; usually does not require discontinuation |
Mean lymphocyte counts fall by approximately 30% during the first year of dimethyl fumarate therapy and then plateau. About 6% of patients drop below 0.5 × 109/L at some point, and 2% develop prolonged severe lymphopenia (≥6 months <0.5 × 109/L). PML in trials and postmarketing experience has occurred almost exclusively in patients with sustained lymphopenia, especially <0.5 × 109/L for prolonged periods, although postmarketing cases at counts <0.9 × 109/L are described. Per the PI, consider interrupting therapy when ALC persists below 0.5 × 109/L for more than six months and continue to monitor counts after stopping — recovery to normal can take many months (median 96 weeks for prolonged severe lymphopenia).
Drug Interactions
Dimethyl fumarate has an unusually clean drug-interaction profile. Because metabolism proceeds via ubiquitous esterases and the tricarboxylic acid cycle rather than cytochrome P450 enzymes, it is neither a substrate, inhibitor, nor inducer of clinically relevant CYPs in vivo. The interactions below reflect overlapping pharmacodynamics with immune-modulating therapies and one mitigation strategy (aspirin) for flushing.
Monitoring
Routine monitoring on dimethyl fumarate centres on the absolute lymphocyte count, hepatic biochemistry, and a high index of suspicion for opportunistic infection — particularly herpes zoster and PML — and for serious gastrointestinal reactions. Monitoring intervals below combine PI requirements and standard MS practice.
-
Complete blood count with lymphocyte differential
Baseline; 6 months after start; then every 6–12 months and as clinically indicated
Routine Consider interruption of therapy when ALC persists below 0.5 × 109/L for more than six months. If discontinuing for lymphopenia, continue measuring ALC until recovery — median time to normalization is 4.3 weeks (mild lymphopenia at d/c), 10.0 weeks (moderate), 16.7 weeks (severe), and 96 weeks for prolonged severe lymphopenia. -
Liver function (ALT, AST, ALP, total bilirubin)
Baseline before initiation; then as clinically indicated during therapy
Routine Most enzyme elevations are <3× ULN and occur in the first 6 months. Discontinue if clinically significant liver injury is suspected (e.g., new transaminase rise >5× ULN with bilirubin >2× ULN, jaundice, dark urine, RUQ pain). -
Symptoms of PML
At each contact; heightened vigilance with prolonged lymphopenia
Routine Withhold therapy at the first sign of progressive hemiparesis, ataxia, visual disturbance, cognitive or personality change, and arrange MRI plus CSF JCV PCR. Patterns may be apparent on MRI before clinical symptoms. -
Signs of herpes zoster and other opportunistic infections
At each contact
Routine Counsel on dermatomal rash, neuralgia, and red-flag symptoms (visual change with vesicles, encephalitis features). Consider withholding dimethyl fumarate during treatment of zoster or other serious infection. -
Anaphylaxis / angioedema awareness
Especially after first dose and during early therapy
Routine Counsel patients to discontinue immediately and seek emergency care for swelling of the face, lips, mouth, or throat, urticaria, or shortness of breath. Do not rechallenge. -
GI symptoms (severe abdominal pain, hematemesis, melena, severe vomiting, severe diarrhea)
At each contact, especially in the first 6 months
Routine Warning added 12/2023 for serious GI reactions (perforation, ulceration, hemorrhage, obstruction), some fatal across fumaric acid esters. Promptly evaluate and discontinue dimethyl fumarate for new or worsening severe GI symptoms. -
Flushing tolerance
During first month and at each visit
Routine Most flushing improves over time. Reinforce administration with food and consider non-enteric-coated aspirin pre-dose for persistent symptoms. -
MRI of brain
Per MS practice (commonly baseline and at intervals to monitor disease activity); additional MRI if PML suspected
Trigger-based Routine MRI is part of MS care rather than dimethyl fumarate-specific monitoring. Any new neurological symptom while on dimethyl fumarate should prompt urgent imaging to differentiate MS relapse from PML. -
Renal function (urinalysis for proteinuria)
Routine clinical follow-up
Trigger-based Asymptomatic albuminuria (~6%) is usually transient and clinically silent; persistent or progressive proteinuria should prompt further evaluation. -
Vaccinations
Before initiation; routine inactivated vaccines during therapy
Trigger-based Complete live and live-attenuated vaccinations (e.g., MMR, varicella) before starting therapy. Inactivated vaccines (tetanus, pneumococcal, meningococcal) elicited normal antibody responses on dimethyl fumarate. Recombinant zoster vaccine is generally preferred over live zoster vaccine in MS DMT-treated patients per AAN.
PML on dimethyl fumarate is rare but devastating. The dominant risk factor is prolonged severe lymphopenia, but cases have occurred at counts <0.9 × 109/L. Any patient with new neurological symptoms — particularly subacute cognitive change, hemiparesis, ataxia, or visual disturbance — should have therapy withheld and undergo urgent MRI plus CSF JCV PCR before treatment is resumed. Differentiating PML from a new MS relapse based on clinical features alone is unreliable.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to dimethyl fumarate or any excipient. Reactions reported include anaphylaxis and angioedema; patients with such reactions must not be rechallenged.
Note: hypersensitivity to dimethyl fumarate or excipients is the only formal contraindication listed in the Tecfidera prescribing information. The cautions below reflect class- and pharmacology-based clinical practice.
Relative Contraindications — Specialist Input Recommended
- Active serious infection, including herpes zoster, opportunistic viral, fungal, or bacterial infection — withhold dimethyl fumarate until the infection is treated and resolved.
- Pre-existing severe lymphopenia (ALC <0.5 × 109/L) — not formally studied; the additive lymphopenia risk argues against initiation.
- Pre-existing moderate lymphopenia (0.5–0.8 × 109/L) — initiate only if benefit clearly outweighs risk; monitor more frequently.
- Active or suspected progressive multifocal leukoencephalopathy.
- Severe active hepatic disease, including drug-induced liver injury attributable to fumarates.
- Recent or planned use of other immunosuppressive disease-modifying therapy without an appropriate washout — risk of cumulative immune compromise.
- Recent or planned live or live-attenuated vaccination.
- Pregnancy planning — discuss benefits and risks; pregnancy registry data through 2022 are reassuring but limited, and animal data show developmental toxicity at clinically relevant doses.
Use With Caution
- Patients with peptic ulcer disease, inflammatory bowel disease, or recent GI bleeding — given the warning for serious GI reactions including perforation, ulceration, and hemorrhage.
- Patients with chronic respiratory disease, JC virus seropositivity, or other PML risk factors — these increase the importance of strict ALC monitoring.
- Concomitant hepatotoxic medications — increased vigilance for liver injury.
- Pregnancy and lactation — see Use in Specific Populations; benefit-risk discussion essential.
- Pediatric patients (<18 years) — safety and effectiveness not established.
Anaphylaxis and angioedema — discontinue and do not restart.
PML — withhold at the first sign or symptom suggestive of PML; the risk is greatest with prolonged severe lymphopenia.
Herpes zoster and other serious opportunistic infections.
Lymphopenia — monitor CBC at baseline, 6 months, then every 6–12 months.
Liver injury — clinically significant hepatic injury reported postmarketing.
Flushing — common at initiation; usually self-limited.
Serious gastrointestinal reactions — perforation, ulceration, hemorrhage, obstruction (warning added 12/2023).
Patient Counselling
Purpose of Therapy
Explain that dimethyl fumarate is a long-term oral medication used to reduce relapses, brain MRI lesions, and the progression of disability in relapsing forms of multiple sclerosis. It does not cure MS, but pivotal trials and long-term extension data show sustained reductions in relapse rate compared with placebo. The capsules contain a delayed-release coating, so they must be swallowed whole — they cannot be opened, crushed, chewed, or sprinkled on food.
How to Take
Begin with one 120 mg capsule by mouth twice daily for the first 7 days, then increase to one 240 mg capsule by mouth twice daily from day 8 onward. The medication can be taken with or without food, but taking it with food often reduces flushing. If flushing remains bothersome, ask the prescriber whether non-enteric-coated aspirin (up to 325 mg) taken about 30 minutes before each dose may help — this is an evidence-based option for short-term use. Store the capsules in their original container, protected from light.
Sources
- Biogen. Tecfidera (dimethyl fumarate) delayed-release capsules — full prescribing information. Revised March 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/204063s031lbl.pdf Authoritative source for indication, dosing, warnings and precautions (including the December 2023 addition of serious gastrointestinal reactions), pharmacokinetics, adverse-reaction tables, and pregnancy registry data through 2022.
- U.S. Food and Drug Administration. DailyMed: Tecfidera (dimethyl fumarate) labelling. Available at: https://dailymed.nlm.nih.gov/ Maintained repository of current FDA-approved labelling for branded and generic dimethyl fumarate products.
- U.S. Food and Drug Administration. Tecfidera (dimethyl fumarate) Information. Available at: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/tecfidera-dimethyl-fumarate-information Postmarket safety updates and communications from the FDA, including the original PML safety communication.
- Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–1107. doi: 10.1056/NEJMoa1114287 (PMID: 22992073) Pivotal Phase III DEFINE trial in relapsing-remitting MS demonstrating dose-dependent reductions in relapse rate and disability progression versus placebo; basis for FDA approval.
- Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–1097. doi: 10.1056/NEJMoa1206328 (PMID: 22992072) Pivotal Phase III CONFIRM trial including a glatiramer acetate reference arm; supported the BID 240 mg dose and the favourable benefit-risk profile reflected in the Tecfidera label.
- Gold R, Arnold DL, Bar-Or A, Fox RJ, Kappos L, Mokliatchouk O, Jiang X, Lyons J, Kapadia S, Miller C. Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results. Mult Scler. 2022;28(5):801–816. doi: 10.1177/13524585211037909 (PMID: 34465252) Final results of the long-term ENDORSE extension showing sustained efficacy and a stable safety profile through up to 13 years of dimethyl fumarate therapy.
- Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, Haboubi M, Halper J, Hosey JP, Jones DE, Lisak R, Pelletier D, Potrebic S, Sitcov C, Sommers R, Stachowiak J, Getchius TSD, Merillat SA, Pringsheim T. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):777–788. doi: 10.1212/WNL.0000000000005347 (Reaffirmed October 2024) AAN consensus practice guideline on starting, switching, and stopping disease-modifying therapies in MS; positions dimethyl fumarate among first-line oral options for relapsing forms.
- Rae-Grant A, Day GS, Marrie RA, et al. Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):789–800. doi: 10.1212/WNL.0000000000005345 Companion systematic review providing the evidence base for the AAN recommendations.
- Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96–120. doi: 10.1177/1352458517751049 Joint European guideline that places dimethyl fumarate among approved DMTs for active relapsing MS, with monitoring guidance for lymphocyte counts and PML risk.
- Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011;134(Pt 3):678–692. doi: 10.1093/brain/awq386 Foundational mechanistic study describing Nrf2-mediated antioxidant and neuroprotective effects of fumarates in models of inflammatory CNS disease.
- European Medicines Agency. Skilarence (dimethyl fumarate) — Summary of Product Characteristics. Almirall. Available via the EMA website. EU label for the dimethyl fumarate monoproduct approved for moderate-to-severe plaque psoriasis (not available in the US); useful comparator for off-label dermatologic use.
- Greenwich Biosciences. Vumerity (diroximel fumarate) — full prescribing information; Banner Life Sciences. Bafiertam (monomethyl fumarate) — full prescribing information. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ FDA labelling for the related fumarate products in the US, sharing the same active species (MMF) but differing in formulation and tolerability profile.