VUMERITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).
Dihydroorotate dehydrogenase (DHODH) inhibitor; reduces proliferation of activated T and B cells by inhibiting pyrimidine synthesis.
| Metabolism | Primarily hydrolyzed by esterases and amidases; minor CYP450 metabolism. Major metabolite is monomethyl fumarate (MMF). |
| Excretion | Primarily eliminated via fecal/biliary routes (approximately 87% of absorbed dose), with only about 10% excreted renally as metabolites. Unchanged drug is not detected in urine. |
| Half-life | Mean terminal elimination half-life is approximately 12 hours (range 10-15 hours) at steady state. This supports twice-daily dosing and allows for rapid attainment of steady state within 2-3 days. |
| Protein binding | Approximately 60-70% bound to plasma proteins, primarily to serum albumin. Binding is independent of concentration in therapeutic range. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is about 100-150 L, roughly 1.4 L/kg for a 70 kg individual. This suggests extensive tissue distribution beyond plasma volume. |
| Bioavailability | Absolute bioavailability of oral diroximel fumarate is not directly determined due to extensive presystemic hydrolysis. However, relative to dimethyl fumarate, the monomethyl fumarate exposure is comparable, with FDA labeling citing a relative bioavailability of approximately 50% compared to an oral solution. |
| Onset of Action | Oral: Clinical effects on MRI lesions (new/newly enlarging T2 lesions) are detectable as early as 8 weeks after initiation of therapy. Maximal reduction in relapse rate is typically seen after 3-6 months. |
| Duration of Action | Duration of action for suppression of disease activity is continuous with regular twice-daily dosing. No significant carry-over effect beyond 12 hours after last dose; missed doses may lead to breakthrough activity. |
| Molecular Weight | 459.56 |
462 mg orally twice daily with or without food.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not recommended in severe renal impairment (GFR <30 mL/min) due to insufficient data. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). Not recommended for moderate hepatic impairment (Child-Pugh B). Use with caution in mild hepatic impairment (Child-Pugh A); no dose adjustment necessary. |
| Pediatric use | Safety and efficacy not established; not approved for pediatric use. |
| Geriatric use | No specific dose adjustment; limited data available, but no age-related pharmacokinetic differences expected. |
| 1st trimester | Avoid due to risk of fetal harm based on animal studies and its mechanism of action. Limited human data. |
| 2nd trimester | Avoid due to potential fetal toxicity; no adequate studies in pregnant women. |
| 3rd trimester | Avoid due to potential fetal toxicity; no adequate studies in pregnant women. |
Clinical note
Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).
| Placental transfer | Crosses placenta in animal studies; expected to cross in humans due to low molecular weight and lipophilicity. |
| Breastfeeding | Not recommended during breastfeeding. Excreted in animal milk; unknown if excreted in human milk. Potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to diroximel fumarate or any component of the formulationConcomitant use with dimethyl fumarate or other fumaratesSevere hepatic impairment
| Precautions | Anaphylaxis and angioedema, Progressive multifocal leukoencephalopathy (PML) in patients with lymphopenia, Lymphopenia, Liver injury including transaminase elevations, Herpes zoster and other serious infections |
| Food/Dietary | Take with food to reduce incidence of flushing and gastrointestinal adverse reactions. Avoid high-fat meals immediately before dosing as they may increase absorption variability. |
| Clinical Pearls |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | Vumerity (diroximel fumarate) is contraindicated in pregnancy. Animal studies have shown fetal harm, including decreased fetal weight, increased skeletal variations, and malformations at doses below the human dose. No adequate human data exist. Risk cannot be ruled out in all trimesters. |
| Fetal Monitoring | Monitor complete blood count (CBC) and liver function tests (LFTs) at baseline and periodically. Watch for lymphopenia, hepatic injury, and hypersensitivity reactions. In pregnancy, perform fetal ultrasound if exposure occurs. |
| Fertility Effects | No human data. In animal studies, no adverse effects on male or female fertility at clinically relevant doses. |
| VUMERITY (diroximel fumarate) is a prodrug of monomethyl fumarate used for relapsing forms of multiple sclerosis. Key pearls: 1) Administer with food to reduce flushing and GI side effects. 2) Flushing may be managed with aspirin 30 minutes prior to dosing. 3) Monitor lymphocytes, LFTs, and renal function periodically. 4) Avoid concomitant dimethyl fumarate or other fumarates. 5) Contraindicated in patients with known hypersensitivity to dimethyl fumarate. |
| Patient Advice | Take VUMERITY with food to minimize flushing and stomach upset. · Flushing is common; taking aspirin 30 minutes before may help. · Swallow capsules whole; do not crush, chew, or open. · Do not take with dimethyl fumarate (Tecfidera) or other fumarate products. · Report any signs of infection, especially lymphopenia-related. · Missed dose: skip if >7 hours late, take next dose at normal time. · Monitor for worsening neurological symptoms and report changes. |