monomethyl fumarate

General

Pronunciation:
mon-oh-meth-il fue-ma-rate

Trade Name(s)

Bafiertam

Ther. Class.

anti-multiple sclerosis agents

Indications

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

Action

Activates nuclear factor (Nrf2) 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: Delayed by ingestion of high-fat meals.

Distribution: Well distributed to extravascular tissues.

Metabolism and Excretion: Metabolized by the tricarboxylic acid cycle. 60% eliminated via exhalation of CO₂ . Minor amounts eliminated by renal (16%) and fecal (1%) routes.

Half-life: 30 min.

TIME/ACTION PROFILE (plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	12 hr

Contraindication/Precautions

Contraindicated in:

Hypersensitivity to monomethyl fumarate, dimethyl fumarate, or diroximel fumarate;
Concurrent use of dimethyl fumarate or diroximel fumarate.

Use Cautiously in:

Serious infections (treatment may be withheld);
Persistent lymphopenia (>6 mo) (↑ risk of progressive multifocal leukoencephalopathy [PML]);
OB: Safety not established in pregnancy;
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, vomiting

GU: albuminuria

Hemat: eosinophilia, 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

Both dimethyl fumarate and diroximel fumarate are metabolized to monomethyl fumarate; concurrent use contraindicated.

Route/Dosage

PO (Adults): 95 mg twice daily for 7 days, then ↑ to 190 mg twice daily.

Availability

Delayed-release capsules: 95 mg

Assessment

Monitor for signs and symptoms of hypersensitivity reactions (difficulty breathing, urticaria, swelling of the throat and tongue) after each dose.
Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus that leads to death or severe disability; withhold dose and notify health care professional promptly. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML ↑ with the number of infusions. Withhold monomethyl fumarate at first sign of PML.
Monitor for signs and symptoms of herpes and other opportunistic infections (fever, chills, lesions on skin or mucous membranes, headache, change in mental status) periodically during therapy.
Monitor for serious GI reactions, including perforation, ulceration, hemorrhage, and obstruction. Discontinuation of therapy may be necessary.

Lab Test Considerations:

Monitor CBC with lymphocyte count prior to starting therapy, after 6 mo of therapy, and every 6–12 mo as clinically indicated. If lymphocyte count <0.5 × 10⁹ /L, consider holding therapy and monitoring lymphocyte count until recovery, even if therapy is discontinued.

Monitor AST, ALT, alkaline phosphatase, and total bilirubin levels before starting therapy and periodically during therapy. Usually resolve when therapy is discontinued. If significant liver injury is suspected, discontinue therapy.

Implementation

PO Administer twice daily without regard to food. DNC: Swallow capsules whole; do not crush, chew, or mix contents with food.
- Administration of non-enteric-coated aspirin (up to 325 mg) 30 min before dosing may ↓ incidence or severity of flushing.

Patient/Family Teaching

Explain purpose and side effects of monomethyl fumarate to patient. Instruct them to take medication as directed and when to ask for pain medication. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Encourage patient to follow up with lab tests to monitor for side effects.
Inform patient that medication may cause flushing. Usually begins at start of therapy and improves or resolves over time. Administration of non-enteric-coated aspirin (up to 325 mg) 30 min before therapy may ↓ the incidence or severity of flushing.
Advise patient to notify health care professional immediately if signs and symptoms of hypersensitivity reactions, PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes; may progress gradually over days to wks), infection, or liver injury occur.
Advise patient to report symptoms of GI ulcer or bleeding (epigastic pain, nausea, black tarry stools, rectal bleeding) or obstruction (abdominal pain, bloating, vomiting, constipation).
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: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage women who become pregnant while taking monomethyl fumarate to enroll in the National Pregnancy Registry MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS) at 1-877-311-8972 or visit http://mothertobaby.org/ongoing-studies.

Evaluation/Desired Outcomes