General

Pronunciation:
dye-meth-il fue-ma-rate

Trade Name(s)

• Tecfidera

Ther. Class.

anti-multiple sclerosis agents

Indications

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

Action

Activates nuclear factor-like 2 pathway involved in cellular response to oxidative stress.

Therapeutic Effect(s):

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

Pharmacokinetics

Absorption: Rapidly converted to active metabolite monomethyl fumarate (MMF) by enzymes in GI tract, blood, and tissue.

Distribution: Unknown.

Metabolism and Excretion: MMF is metabolized by the tricarboxylic acid cycle. 60% eliminated via exhalation of CO₂ . Minor amounts eliminated by renal (16%) and fecal (1%) routes; trace amounts in urine.

Half-life: MMF:  1 hr

TIME/ACTION PROFILE (effects on disability)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity.

Use Cautiously in:

• Serious infections (treatment may be withheld);
• Persistent lymphopenia (>6 mo) (↑ risk of progressive multifocal leukoencephalopathy [PML]);
• OB:  Other agents preferred when disease-modifying therapy needed;
• Lactation: Safety not established in breastfeeding;
• Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

Derm: flushing, erythema, pruritus, rash

GI: abdominal pain, diarrhea, nausea, dyspepsia, GI HEMORRHAGE, GI OBSTRUCTION, GI PERFORATION, GI ULCERATION, HEPATOTOXICITY, ↑ liver enzymes, vomiting

Hemat: lymphopenia

Neuro: PML

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema), INFECTION (bacterial, viral [especially herpes zoster], and fungal)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

PO (Adults): 120 mg twice daily for one wk, then 240 mg twice daily.

Availability (generic available)

Extended-release capsules: 120 mg, 240 mg

Assessment

• Monitor for signs and symptoms of infections (fever, sore throat, herpes zoster, fungal and bacterial infections). Consider withholding medication until serious infections are resolved.
• 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 wks. Withhold medication and obtain diagnostic evaluation.
• Monitor for signs and symptoms of hypersensitivity reactions (difficulty breathing, urticaria, swelling of throat and tongue) during therapy.
• Monitor for new or worsening severe GI signs and symptoms (vomiting, abdominal pain, GI bleeding). Discontinue therapy if severe GI signs or symptoms develop.

Lab Test Considerations:

Monitor CBC with lymphocyte count before initiating therapy, after 6 mo, and every 6–12 mo thereafter. If lymphocyte count is <0.5 × 10⁹ /L for >6 mo, may interrupt therapy. Consider withholding therapy for patients with serious infections.

• Assess AST, ALT, alkaline phosphatase, and total bilirubin levels prior to starting therapy and as clinically indicated. May cause ↑ AST and ALT. Discontinue therapy if clinically significant liver injury is suspected.
• May cause transient ↑ mean eosinophil count during first 2 mo of therapy.

Implementation

• PO Administer 120 mg twice daily for 7 days then increase to maintenance dose of 240 mg twice daily without regard to food. For patients with difficulty tolerating maintenance dose, may temporarily decrease to 120 mg twice daily; resume maintenance dose within 4 wk.  DNC: Swallow capsules whole; do not open, crush, chew, or sprinkle on food.  Discard any unused capsules 90 days after opening.

Patient/Family Teaching

• Instruct patient to take dimethyl fumarate as directed. 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 dimethyl fumarate with food or administration of nonenteric coated aspirin (up to a dose of 325 mg) 30 min prior to dimethyl fumarate dosing may decrease incidence or severity of flushing.
• Advise patient to notify health care professional if signs or symptoms of infections or liver injury (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) occur.
• Advise patient to notify health care professional promptly if signs and symptoms of PML (new or worsening weakness; trouble using their arms or legs; changes to thinking, eyesight, strength, or balance), GI events (rectal bleeding, bloody diarrhea, vomiting blood, severe abdominal pain, severe vomiting, severe diarrhea), 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.
• Rep:  Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Decreased incidence/severity of relapse of MS.