Deroximel DR

Approved Indications:

• Relapsing forms of multiple sclerosis (MS), including:
• Clinically isolated syndrome (CIS)
• Relapsing-remitting multiple sclerosis (RRMS)
• Active secondary progressive multiple sclerosis (SPMS)

Note: Approved for adult use only.

Route of Administration: Oral

Recommended Dose:

• Initial dose: 231 mg twice daily for the first 7 days
• Maintenance dose: 462 mg twice daily, starting on day 8

Administration Instructions:

• Can be taken with or without food, but taking with food may reduce the risk of gastrointestinal (GI) side effects
• Swallow capsules whole; do not crush, chew, or sprinkle contents

Missed Dose:

• If a dose is missed, take the next dose at the scheduled time; do not double the dose

Pediatric Use:

• Safety and efficacy not established in pediatric populations

Elderly Use:

• No dosage adjustment required, but monitor renal function and tolerance closely

Renal/Hepatic Impairment:

• Not recommended in patients with severe renal impairment
• Use caution in moderate to severe hepatic impairment

Diroximel fumarate is a fumaric acid ester prodrug that is rapidly converted to its active metabolite monomethyl fumarate (MMF). MMF activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which plays a central role in cellular defense against oxidative stress. By promoting the expression of antioxidant and cytoprotective genes, MMF reduces inflammation and oxidative damage in the central nervous system (CNS). Additionally, MMF modulates immune responses, reducing the number of pro-inflammatory lymphocytes and thereby lowering disease activity in multiple sclerosis.

• Absorption: Rapidly converted to MMF after oral administration; peak plasma concentration (Tmax) of MMF occurs ~2.5 to 3 hours post-dose
• Bioavailability: Not directly determined for diroximel fumarate, but MMF is systemically available
• Distribution: MMF has a moderate volume of distribution
• Metabolism: Diroximel fumarate undergoes enzymatic hydrolysis via esterases to MMF; further metabolism via the tricarboxylic acid (TCA) cycle
• Half-life: MMF terminal half-life ~1 hour
• Excretion: Primarily exhaled as CO₂ (~60%), with smaller amounts excreted in urine (~15%) and feces (~1%)

• Pregnancy:
• Animal studies showed adverse fetal effects at high doses
• No adequate data in pregnant women
• Use only if potential benefit justifies potential risk
• Lactation:
• Unknown if MMF is excreted in human milk
• Risk to the infant is not clearly established; use caution

• Primary Class: Immunomodulatory agent
• Subclass: Fumaric acid derivative
• Indication Class: Disease-modifying therapy (DMT) for relapsing multiple sclerosis

• Known hypersensitivity to diroximel fumarate, dimethyl fumarate, or any component of the formulation
• Concomitant severe gastrointestinal disorders, as symptoms may be exacerbated
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)

• Lymphopenia: Diroximel fumarate can cause decreased lymphocyte counts; monitor CBCs before starting and during treatment
• Progressive multifocal leukoencephalopathy (PML): Rare but serious; monitor for neurologic symptoms
• Liver injury: Elevations in liver enzymes may occur; monitor liver function periodically
• Flushing and GI reactions: Common adverse effects; generally mild and transient
• Infections: Increased risk with lymphopenia; counsel patients to report signs of infection promptly

Common (>10%):

• Gastrointestinal: Nausea, diarrhea, abdominal pain
• General: Flushing, warmth, pruritus

Less Common (1–10%):

• Vomiting
• Dyspepsia
• Increased liver enzymes
• Lymphopenia

Serious/Rare (<1%):

• Progressive multifocal leukoencephalopathy (PML)
• Hepatotoxicity
• Anaphylaxis or angioedema
• Severe lymphopenia

Onset: Flushing and GI symptoms typically occur early in treatment (within first month)

• Live vaccines: Avoid during treatment due to immunosuppressive effect
• Immunosuppressants/Immunomodulators: Caution when used concurrently; may increase risk of infection or lymphopenia
• No CYP450 interactions: Diroximel fumarate and MMF are not metabolized via CYP enzymes
• Alcohol: No known interaction, but may increase GI side effects

• Diroximel fumarate is recognized as an alternative to dimethyl fumarate with improved gastrointestinal tolerability
• Included in recent MS treatment algorithms (AAN, ECTRIMS) as a first-line oral therapy for relapsing MS
• Ongoing studies are evaluating long-term lymphopenia risk and comparative GI tolerability with dimethyl fumarate

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Excursion permitted to: 15°C to 30°C (59°F to 86°F)
• Humidity/Light: Store in original container; protect from moisture
• Handling: Keep capsules in the blister pack until use; do not crush or chew