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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Delayed Release, Oral:
Tecfidera: 120 mg, 240 mg [contains brilliant blue fcf (fd&c blue #1)]
Tecfidera: Capsule, delayed release: 120 mg (14s) and Capsule, delayed release: 240 mg (46s) (60 ea) [contains brilliant blue fcf (fd&c blue #1)]
Brand Names: U.S.
- Fumaric Acid Derivative
- Immunomodulator, Systemic
DMF and its active metabolite, monomethyl fumarate (MMF), have been shown to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is involved in cellular response to oxidative stress. The mechanism by which dimethyl fumarate (DMF) exerts a therapeutic effect in MS is unknown, although it is believed to result from its anti-inflammatory and cytoprotective properties via activation of the Nrf2 pathway (Fox, 2012; Gold, 2012).
Vd: MMF: 53 to 73 L
Undergoes rapid and extensive presystemic hydrolysis by esterases to its active metabolite, monomethyl fumarate (MMF); MMF is further metabolized via the tricarboxylic acid (TCA) cycle. Major serum metabolites include: MMF, fumaric acid, citric acid, and glucose.
CO2 via exhalation (~60%); urine (16%; trace amounts as unchanged MMF), feces (1%)
Time to Peak
2 to 2.5 hours; delayed to 5.5 hours with food
MMF: ~1 hour
MMF: 27% to 45%
Use: Labeled Indications
Multiple sclerosis: Treatment of patients with relapsing forms of multiple sclerosis
Known hypersensitivity to dimethyl fumarate or any component of the formulation
Multiple sclerosis (relapsing): Oral: Initial: 120 mg twice daily; after 7 days, increase to the maintenance dose: 240 mg twice daily
Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
No dosage adjustment necessary.
Dosing: Adjustment for Toxicity
Flushing, GI intolerance, or intolerance to maintenance dose: Consider temporary dose reduction to 120 mg twice daily (resume recommended maintenance dose of 240 mg twice daily within 4 weeks). Consider discontinuation in patients who cannot tolerate return to the maintenance dose.
Hepatic injury (suspected drug-induced), clinically significant: Discontinue treatment.
Lymphocyte count <500/mm3 persisting for >6 months: Consider treatment interruption.
Serious infection: Consider withholding treatment until infection resolves.
Oral: Swallow capsules whole and intact; do not crush, chew, open the capsule, or sprinkle contents on food. Administer with or without food; administering with food may decrease the incidence of flushing. Administration of aspirin (nonenteric coated up to a dose of 325 mg) 30 minutes prior to dimethyl fumarate may also reduce the incidence of flushing.
Store at 15°C to 30°C (50°F to 86°F). Protect capsules from light and store in the original container.
Vaccines (Live): Dimethyl Fumarate may enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification
Cardiovascular: Flushing (40%)
Gastrointestinal: Abdominal pain (18%), diarrhea (14%), nausea (12%)
Infection: Infection (60%; placebo: 58%)
1% to 10%:
Dermatologic: Pruritus (8%), skin rash (8%), erythema (5%)
Gastrointestinal: Vomiting (9%), dyspepsia (5%)
Genitourinary: Proteinuria (6%)
Hematologic: Lymphocytopenia (2% to 6%)
Hepatic: Increased serum AST (4%)
<1% (Limited to important or life-threatening: Anaphylaxis, angioedema, eosinophilia (transient), progressive multifocal leukoencephalopathy
Concerns related to adverse effects:
• Dermatitis/irritation: May cause rash, pruritus, or erythema. There are case reports of contact dermatitis resulting from dimethyl fumarate (DMF) exposure after use as a fungicide and desiccant in the shipping of furniture (Bruze 2011; Giménez-Arnau 2011; Ropper 2012).
• Flushing: Commonly causes mild to moderate flushing (eg, warmth, redness, itching, burning sensation); flushing generally appears soon after initiation, and improves or resolves with subsequent dosing. Administration with food may decrease flushing incidence. Administration of aspirin (nonenteric coated ≤325 mg) 30 minutes prior to dimethyl fumarate or a temporary dose reduction may also reduce the incidence and severity of flushing.
• Gastrointestinal events: GI events (eg, nausea, vomiting, diarrhea, abdominal pain, dyspepsia) commonly occur with use; GI events generally occur in the first month of use and decrease thereafter. To improve tolerability, administer with food or temporarily reduce the dosage.
• Hepatotoxicity: Clinically significant postmarketing cases of hepatic injury have been reported, with an onset ranging from a few days to several months after treatment initiation. Signs/symptoms of hepatic injury, including transaminase elevations >5 times the upper limit of normal (ULN) and total bilirubin elevations >2 times ULN have been observed. Some cases have required hospitalization; however, none of the cases were fatal or resulted in liver failure or transplant. Liver function test abnormalities resolved upon discontinuation. Drug-induced hepatocellular injury resulting in new-onset transaminase elevations combined with increased bilirubin levels is an important predictor of serious hepatic injury that may lead to acute hepatic failure, liver transplant, or death in some patients. Transaminase elevations (usually <3 times ULN) were observed in clinical trials, generally occurring in the first 6 months of treatment. Transaminase elevations ≥3 times ULN occurred rarely. Monitor liver function tests prior to treatment initiation and during treatment. Discontinue treatment if dimethyl fumarate-induced hepatic injury is suspected.
• Hypersensitivity reactions: Anaphylaxis and angioedema may occur after the first dose or at any time during treatment. Discontinue therapy if signs and symptoms of anaphylaxis or angioedema occur.
• Lymphopenia: Decreased lymphocyte counts may occur. Obtain a complete blood cell count (CBC), including lymphocyte count, prior to initiation of therapy, after 6 months of treatment, every 6 to 12 months thereafter, and as clinically indicated. Consider therapy interruption in patients with lymphocyte counts <500/mm3 persisting >6 months and in patients with serious infections. Due to a potential for delayed lymphocyte recovery following treatment interruption or discontinuation, monitor lymphocyte counts until lymphopenia is resolved. The decision to restart dimethyl fumarate should be individualized based on clinical circumstances. Dimethyl fumarate has not been studied in patients with preexisting low lymphocyte counts.
• Proteinuria: In clinical trials, proteinuria was reported at a slightly higher incidence than that observed with placebo; significance of these findings is unknown.
• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) has been reported in patients with multiple sclerosis treated with dimethyl fumarate, including fatality (case report). PML may be associated with persistent (>6 months) lymphopenia, with a majority of cases occurring in patients with lymphocyte counts <500/mm3 (although the exact role of lymphopenia in PML is unknown). Withhold therapy immediately at the first sign or symptom suggestive of PML (eg, progressive weakness on one side of the body or clumsiness of limbs; vision disturbances; mental status changes) and perform a diagnostic evaluation (MRI findings may appear before clinical signs/symptoms).
Concomitant drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
• Appropriate use: Dimethyl fumarate should only be prescribed by health care providers who are experienced in the diagnosis and management of multiple sclerosis.
CBC including lymphocyte count (obtained prior to initiation of therapy, after 6 months of treatment, then every 6 to 12 months thereafter and as clinically necessary); liver function tests (transaminases, alkaline phosphatase, total bilirubin) prior to treatment initiation and during treatment as clinically indicated; urinalysis (if proteinuria suspected and/or clinically indicated). Monitor for signs/symptoms of hypersensitivity, infections, and/or progressive multifocal leukoencephalopathy.
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies.
Women exposed to dimethyl fumarate during pregnancy are encouraged to enroll in the Pregnancy Registry by calling 866-810-1462 or visiting www.tecfiderapregnancyregistry.com.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience flushing, abdominal pain, diarrhea, vomiting, or nausea. Have patient report immediately to prescriber signs of infection or signs of progressive multifocal leukoencephalopathy (confusion, depression, memory impairment, behavioral changes, change in strength on one side is greater than the other, difficulty speaking, change in balance, or vision changes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about dimethyl fumarate
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Other brands: Tecfidera