Section 04 · Monograph

Diroximel fumarate

Reviewed Nov 2026FDA label

VumerityNrf2 activator

Indications

Treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive diseaseFDA-labeled

Prodrug that is rapidly converted (via esterases) to monomethyl fumarate (MMF), its active metabolite, which is also the primary active metabolite of dimethyl fumarate
Exact mechanism in MS is not fully understood; MMF activates the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway involved in the cellular antioxidant stress response
MMF also acts as an agonist at the nicotinic acid (HCA2) receptor in vitro

Starting dose: 231 mg orally twice daily for 7 days
Maintenance dose: 462 mg (given as two 231 mg capsules) orally twice daily thereafter
For persistent intolerability, temporary reduction to 231 mg twice daily may be considered
Swallow capsules whole and intact; do not crush, chew, or sprinkle contents
Avoid high-fat, high-calorie meals (may reduce tolerability); avoid co-administration with alcohol
Non-enteric-coated aspirin (up to 325 mg) 30 minutes before dosing may reduce flushing
If switching from dimethyl fumarate, Vumerity may be started the day after discontinuing dimethyl fumarate

Known hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients
Concurrent use with dimethyl fumarate (Tecfidera), because diroximel fumarate is also metabolized to monomethyl fumarate

Contraindicated with dimethyl fumarate due to overlapping active metabolite (MMF)
No clinically meaningful CYP450-mediated interactions (diroximel fumarate/MMF are not metabolized via CYP450 pathways)
No relevant pharmacokinetic interaction with oral contraceptives
Aspirin and alcohol do not clinically alter MMF pharmacokinetics
Effect on immune response to non-live vaccines appears adequate based on dimethyl fumarate data; live/live-attenuated vaccines not studied

Flushing (~40% vs 6% placebo), generally mild-to-moderate
Abdominal pain (~18%), diarrhea (~14%), nausea (~12%), vomiting
Pruritus, rash, dyspepsia, and elevated liver enzymes
Lymphopenia — mean lymphocyte counts decrease ~30% in the first year; 6% develop counts <0.5×10⁹/L
Progressive multifocal leukoencephalopathy (PML) risk with prolonged lymphopenia
Serious infections, including disseminated/atypical herpes zoster
Serious gastrointestinal events postmarketing (perforation, ulceration, hemorrhage, obstruction); acute pancreatitis reported
Anaphylaxis and angioedema, can occur after the first dose or at any time
Clinically significant liver injury reported postmarketing, onset from days to several months after starting

Obtain CBC with lymphocyte count before initiating treatment
Repeat CBC with lymphocyte count at 6 months, then every 6–12 months thereafter
Consider interruption of treatment if lymphocyte count <0.5×10⁹/L persists for more than 6 months
Obtain baseline serum aminotransferases, alkaline phosphatase, and total bilirubin; monitor as clinically indicated
Withhold treatment at first sign or symptom suggestive of PML and evaluate promptly
Consider withholding treatment during serious infection until resolved

Pregnancy: animal data showed adverse fetal effects (skeletal abnormalities, increased mortality, decreased body weight, neurobehavioral impairment) at clinically relevant exposures — may cause fetal harm
Human data from the dimethyl fumarate pregnancy registry (2013–2022, 362 live births/stillbirths) showed a 3.6% major birth defect rate, with no specific pattern of malformation identified
Vumerity Pregnancy Registry available for enrollment (1-833-569-2635 / www.vumeritypregnancyregistry.com)
Lactation: no data on presence of diroximel fumarate or its metabolites in human milk, or on effects on the breastfed infant or milk production