dye-ROX-i-mel FYOO-ma-rate

Therapeutic Classification: anti-multiple sclerosis agents

• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

• Activates nuclear factor (Nrf2) pathway involved in cellular response to oxidative stress.

• Decreased incidence/severity of relapse with decreased progression of lesions and disability.

Absorption: Following oral administration, rapidly converted to active metabolite, monomethyl fumarate (MMF), by enzymes in GI tract, blood, and tissue. Absorption decreased by high-fat, high-calorie food.

Distribution: Well distributed to extravascular tissues.

Metabolism/Excretion: MMF is metabolized by the tricarboxylic acid (TCA) cycle. MMF eliminated via exhalation of CO₂. Inactive metabolites eliminated in urine.

Half-life: MMF: 1 hr.

(MMF plasma concentrations)

Contraindicated in:

• Hypersensitivity to diroximel fumarate or dimethyl fumarate
• Concurrent use of dimethyl fumarate
• Moderate or severe renal impairment.

Use Cautiously in:

• Serious infections (treatment may be withheld)
• Persistent lymphopenia (>6 mo) (↑ risk of PML)
• OB: Safety not established in pregnancyUse during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Safety not established in breastfeedingUse while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children.

Derm: flushing, erythema, pruritus, rash.

GI: abdominal pain, diarrhea, nausea, dyspepsia, HEPATOTOXICITY, vomiting.

GU: albuminuria.

Hemat: eosinophilia, lymphopenia.

Neuro: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML).

Misc: INFECTION (BACTERIAL, VIRAL [ESPECIALLY HERPES ZOSTER], AND FUNGAL), HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA).

Drug-Drug:

• Alcohol may ↓ MMF levels; avoid concurrent use.

• PO (Adults): 231 mg twice daily for 1 wk, then 462 mg twice daily.

• Capsules: 231 mg;

• Monitor for signs and symptoms of anaphylaxis and angioedema (difficulty breathing, urticaria, swelling of throat and tongue) after first dose and during therapy.
• Monitor for signs and symptoms of PML (progressive weakness on one side of body or clumsiness of limbs, disturbance of vision, changes in thinking, memory, and orientation causing confusion and personality changes). Symptoms are diverse, progress over days to weeks. Withhold medication and obtain diagnostic evaluation.

• Obtain CBC with lymphocyte count and serum AST, ALT, alkaline phosphatase and total bilirubin before starting therapy.
  • Monitor CBC with lymphocyte count 6 mo after starting therapy and every 6–12 mo during therapy. May interrupt therapy in patients with lymphocyte counts <0.5 × 10⁹ /L persisting for more than 6 mo.
  • Monitor serum AST, ALT, alkaline phosphatase, and total bilirubin levels during therapy as clinically indicated. If clinically significant liver injury from therapy is suspected, discontinue therapy.

• Administration with food and up to 325 mg non-enteric coated aspirin 30 min before dose to reduce incidence and severity of flushing.
• PO: Administer twice daily. DNC: Swallow capsules whole; do not open, crush, chew or sprinkle capsule contents on food. If taken with food, avoid high-fat, high-calorie meals or snacks; meal/snack should contain ≤700 calories and ≤30 g fat. Avoid administration with alcohol.

• Instruct patient to take medication as directed. A starter dose bottle will be initially provided. Avoid administration with alcohol. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Caution patient not to share medication with others, even if they have the same symptoms; may be dangerous.
• May cause flushing (warmth, redness, itching, and/or burning sensation). Usually begins after starting and resolves over time. Administration of diroximel fumarate with food or administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to diroximel fumarate dosing may decrease incidence or severity of flushing.
• Advise patient to notify health care professional promptly if signs and symptoms of PML (new or worsening weakness; trouble using arms or legs; or changes to thinking, eyesight, strength or balance), liver injury (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice), infection (herpes zoster or others), or hypersensitivity reactions (difficulty breathing, urticaria, swelling of throat and tongue) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize importance of routine lab test to monitor for side effects.

• Decreased incidence/severity of relapse with decreased progression of lesions and disability.

Vumerity

NDC Code^*

• 64406- Biogen Inc.
  • 64406-020- Vumerity
    • 64406-020-01- 1 BOTTLE, PLASTIC in 1 CARTON (64406-020-01) > 106 CAPSULE in 1 BOTTLE, PLASTIC

• 64406- Biogen Inc.
  • 64406-020- Vumerity
    • 64406-020-03- 1 BOTTLE, PLASTIC in 1 CARTON (64406-020-03) > 120 CAPSULE in 1 BOTTLE, PLASTIC

• 64406- Biogen Inc.
  • 64406-020- Vumerity
    • 64406-020-05- 1 BOTTLE, PLASTIC in 1 CARTON (64406-020-05) > 106 CAPSULE in 1 BOTTLE, PLASTIC