Diroximel Fumarate

Diroximel Fumarate Uses, Dosage, Side Effects, Food Interaction and all others data.

Multiple Sclerosis (MS) is a chronic, debilitating neurological disease that can lead to profound cognitive and physical symptoms, severely affecting quality of life. It is the main cause of neurological disability not caused by trauma in the young adult population of both North America and Europe. Relapsing-remitting forms of MS lead to neurological symptoms that resolve and recur periodically. More than 80% of patients suffering from this disease have relapsing-remitting MS.

Diroximel Fumarate is a new drug from the fumarate class formulated to treat various relapsing forms of MS. This drug is bioequivalent to Dimethyl fumarate(initially manufactured in 2013), but is less likely to cause gastrointestinal side effects, owing to its unique chemical structure. Diroximel Fumarate was formulated by Alkermes in collaboration with Biogen, and approved by the FDA on October 30, 2019.

Diroximel Fumarate relieves the neurological symptoms of relapsing MS with less gastrointestinal effects than its bioequivalent counterpart, dimethyl fumarate. It is important to note that diroximel fumarate can cause angioedema, anaphylaxis, hepatotoxicity, flushing, lymphopenia, and Progressive Multifocal Leukoencephalopathy (PML).

Diroximel Fumarate
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Diroximel Fumarate
Generic	Diroximel fumarate
Diroximel fumarate Other Names	Diroximel fumarate
Weight	231mg
Type	Oral delayed release capsule
Formula	C₁₁H₁₃NO₆
Weight	Average: 255.226 Monoisotopic: 255.074287143
Protein binding	Plasma protein binding of MMF, the active metabolite of diroximel fumarate, ranges from 27-45%.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Diroximel Fumarate is a drug used for the treatment of relapsing forms of Multiple Sclerosis (MS).

Diroximel Fumarate is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults; specifically active secondary progressive disease and clinically isolated syndrome, as well as relapsing-remitting MS.

Diroximel Fumarate is also used to associated treatment for these conditions: Active secondary progressive Multiple Sclerosis, Clinically Isolated Syndrome (CIS), Relapsing Remitting Multiple Sclerosis (RRMS)

How Diroximel Fumarate works

Currently, the mechanism of action of this drug in MS is not fully understood. Diroximel Fumarate is hypothesized to regulate cell signaling pathways, causing beneficial immune and neuroprotective effects. Monomethyl fumarate (MMF) is the active metabolite of diroximel fumarate, and activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in humans. This pathway occurs as a response to oxidative stress in cells.

In addition to the above, MMF is a nicotinic acid receptor agonist in the laboratory setting. The relevance of this finding to the treatment of MS is unknown at this time. The mechanism by which this drug leads to less gastrointestinal effects is purported to be due to its lack of a methanol leaving group in its chemical structure, and substitution with inert 2-hydroxyethyl succinimide.

Toxicity

Currently, an MSDS for diroximel fumarate is unavailable. The MSDS for its bioequivalent counterpart, dimethyl fumarate, indicates an oral LD50 of 2,240 mg/kg in rats.

There is no information regarding overdose on the FDA label for diroximel fumarate. Cases of overdose with its bioequivalent counterpart, dimethyl fumarate, have been reported in the literature, and symptoms reflect the adverse effects of this drug. These symptoms include nausea, vomiting, diarrhea, and flushing, among others. Currently there is no antidote to an overdose with diroximel fumarate or dimethyl fumarate. Symptomatic and supportive management are the only options up to this date if an overdose should occur.

Food Interaction

Avoid alcohol.
Take with or without food. If taken with food, the meal/snack should contain no more than 700 calories and no more than 30 g fat. Taking diroximel fumarate with food may reduce the adverse effect of flushing.

Volume of Distribution

The apparent volume of distribution ranges from 72L to 83L. Monomethyl fumarate (MMF), the active metabolite of diroximel fumarate, crosses the blood brain barrier.

Elimination Route

Diroximel Fumarate is rapidly absorbed in the gastrointestinal tract following administration, like its bioequivalent drug, dimethyl fumarate. The median Tmax of monomethyl fumarate (MMF) after oral administration ranges from 2.5-3 hours with a mean Cmax of 2.11 mg/L. The bioequivalent drug, dimethyl fumarate, administered to healthy volunteers also shows a similar mean Tmax and Cmax.

The average steady state concentration of this metabolite is estimated at 8.32 mg.hr/L after it is administered twice a day in patients with MS. The mean AUC0–∞ of the active metabolite is 88mg × min L−1. Food appears to significantly reduce the Cmax of diroximel fumarate's active metabolite, MMF, when compared to administration in the fasted state.

Half Life

The terminal half-life of monomethyl fumarate (MMF), diroximel fumarate's active metabolite, is estimated to be 1 hour.

Clearance

No clearance information is available on the FDA label for diroximel fumarate, however, clinical study results for its active metabolite, monomethyl fumarate show a mean apparent total clearance from the plasma after oral administration of 1.54 mgL−1.

Elimination Route

Monomethyl fumarate is eliminated as carbon dioxide through expired breath. Negligible amounts, under 0.3% of the ingested dose, are measured in urine. The inactive metabolite, 2-hydroxyethyl succinimide (HES), representing 58-63% of the ingested dose, is excreted in urine.