A rare but potentially fatal adverse effect may be PML, which has been observed under treatment with dimethyl fumarate. Overdose
No specific antidote is known. Adverse effects caused by overdosing diroximel fumarate are treated symptomatically. Interactions
Diroximel fumarate does not interact with cytochrome P450 enzymes or P-glycoprotein. Its active metabolite, monomethyl fumarate, has a relatively low plasma protein binding of 27 to 45%. Therefore, its potential for pharmacokinetic interactions is considered to be low.Inactivated vaccines can be given under diroximel fumarate therapy, based on experience with other immunosuppressant drugs, such as studies with tetanus, pneumococcal and meningococcal vaccines. No studies regarding the effectiveness of these vaccines under diroximel fumarate have been conducted. No data are available regarding combination with live vaccines, chemotherapy or immunosuppressants. Nephrotoxicity could be increased when the drug is combined with aminoglycoside antibiotics, diuretics, NSAIDs or lithium. Pharmacology
Mechanism of action
The drugs mechanism of action is not well understood. In preclinical studies it activated nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that is up-regulated under oxidative stress. Pharmacokinetics
The pharmacokinetics of diroximel fumarate has been found to be practically identical to that of dimethyl fumarate. Both are prodrugs of monomethyl fumarate.Taking the drug with a high-calorie, high-fat meal slows down absorption, but has no relevant effect on overall absorption. The US label recommends not taking the drug together with high-calorie and high-fat meals.After ingestion, the substance is cleaved by esterase enzymes before reaching the systemic circulation, resulting in monomethyl fumarate (MMF), the active metabolite, and hydroxyethyl succinimide (HES), which is inactive.
of women without a history of reproductive problems found that about 5% of women had an arcuate uterus when they defined an arcuate uterus any fundal protrusion into the cavity that had an apical angle of more than 90 degrees. Accordingly, it was the most common uterine anomaly, followed by septate uterus (3%) and bicornuate uterus (0.5%). References


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