Dimethyl fumarate
Multiple sclerosis disease-modifying therapies
Multiple sclerosis disease-modifying therapies
An oral fumarate for relapsing multiple sclerosis that activates the Nrf2 antioxidant pathway; flushing and GI upset are common, lymphopenia is watched.
Quick facts
- Group
- Multiple sclerosis disease-modifying therapies
- Target
- KEAP1, the protein that controls the transcription factor Nrf2
- Used for
- Relapsing forms of multiple sclerosis
- Key effects
- Flushing · Abdominal pain
- Monitor
- Complete blood count · Aminotransferases
- ATC
- L04AX07
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows dimethyl fumarate bound to the BTB domain of human KEAP1, the protein that keeps Nrf2 switched off.
Dimethyl fumarate is rapidly converted by esterases to its active metabolite, monomethyl fumarate. Both activate the Nrf2 pathway, the cell's main antioxidant response, and have several immunomodulatory effects; the exact mechanism in multiple sclerosis is unknown. Monomethyl fumarate also activates the nicotinic acid receptor, which may explain flushing.
- Esterases convert dimethyl fumarate to monomethyl fumarate
- Fumarates act on KEAP1 and the Nrf2 pathway switches on
- Antioxidant and immunomodulatory genes switch on
- Fewer relapses; lymphocyte counts can fall
Indications
- Relapsing forms of multiple sclerosis in adults Multiple sclerosis →
Adverse effects
Common
- Flushing (warmth, redness, itching), mostly early and improving over time
- Abdominal pain, diarrhoea and nausea
Contraindications
- Known hypersensitivity to dimethyl fumarate or excipients
Key interactions
- Other immunosuppressants or MS therapies
- Additive lowering of lymphocytes and infection risk
What is monitored
- Complete blood count with lymphocytes before starting, at 6 months and every 6 to 12 months
- Aminotransferases, alkaline phosphatase and bilirubin before starting and as needed
- New neurological symptoms (PML)
Administration and safety
- Capsules are swallowed whole: not crushed, chewed or sprinkled on food
- A lower starting dose for the first week improves tolerance
- Taking it with food can reduce flushing
Pregnancy and breastfeeding
Registry and observational data have not shown more major birth defects or miscarriage; animal studies showed effects on offspring.
Nursing care
- Explain that flushing and stomach upset are common and usually improve
- Teach signs of allergy (swelling of throat or tongue, trouble breathing) and of PML
- Report severe abdominal pain, black stools or vomiting blood
Pharmacokinetics
- Absorption
- Delayed-release capsule; not detectable in plasma because esterases convert it before it reaches the circulation
- Metabolism
- Monomethyl fumarate is further metabolized through the citric acid cycle, without cytochrome P450
- Half-life
- Monomethyl fumarate about 1 hour
Test yourself
Think of the answer, then tap the question to see it.
What is the active metabolite of dimethyl fumarate?
Monomethyl fumarate.
Which transcription pathway do fumarates activate?
The Nrf2 antioxidant pathway.
Which blood count is monitored and why?
Lymphocytes: prolonged lymphopenia is linked to PML.
Connections
← Back to the class: Multiple sclerosis disease-modifying therapies
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - DIMETHYL FUMARATE capsule, delayed release (DailyMed (U.S. National Library of Medicine), 2026); Dimethyl Fumarate: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 7X4W: Crystal structure of Keap1 BTB domain in complex with dimethyl fumarate (DMF) (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.