VUMERITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).

How it works

Dihydroorotate dehydrogenase (DHODH) inhibitor; reduces proliferation of activated T and B cells by inhibiting pyrimidine synthesis.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for 48 hours after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to diroximel fumarate or its components","Concomitant use with dimethyl fumarate"]

Clinical Precautions

Precautions

["Anaphylaxis and angioedema","Progressive multifocal leukoencephalopathy (PML) in patients with lymphopenia","Lymphopenia","Liver injury including transaminase elevations","Herpes zoster and other serious infections"]

Clinical Tips & Counseling

Drug interactions

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VUMERITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).

How it works

Dihydroorotate dehydrogenase (DHODH) inhibitor; reduces proliferation of activated T and B cells by inhibiting pyrimidine synthesis.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VUMERITY (VUMERITY).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for 48 hours after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to diroximel fumarate or its components","Concomitant use with dimethyl fumarate"]