Multiple sclerosis Tecfidera protocol and monitoring

Dimethyl fumarate, initially dosed at 120 mg twice daily and then increased to 240 mg, may cause flushing, gastrointestinal issues, lymphopenia, PML, and liver toxicity. Pre-treatment checks include blood tests, urinalysis, and MRI. Ongoing monitoring involves blood counts, liver function, and annual MRI. Discontinuation is advised for significant liver injury.

Initial Dose and Side Effects:

The starting dose for oral dimethyl fumarate is 120 mg given twice daily.

After seven days, the dose should be increased to 240 mg given twice daily.

The most common side effects of dimethyl fumarate are flushing gastrointestinal symptoms, including diarrhea, nausea, and abdominal pain, lymphopenia, progressive multifocal leukoencephalopathy (PML), and liver toxicities. (1, 2, 3)

Pre-Treatment Monitoring:

Before Initiation of therapy :

CBC, bilirubin, liver enzymes, TSH, urinalysis, urinary albumin, creatinine ratio, JCV index

HBsAg, anti-HBs, anti-HBc, Hepatits C, HIV, VZV serology

Vaccination status verified and updated if necessary

Pneumococcus and Haemophilus influenza type B vaccines

Recent brain MRI (<3 months)

Ongoing Monitoring During Treatment:

CBC, liver enzymes, creatinine, bilirubin,TSH every 2months for 6 months then every 6 months

Urinalysis every 6months, If proteinuria then do urinary albumin to creatinine ratio; and if abnormal, a 24 hrs urine collection for protein and creatinine is essential.

Annual brain MRI

Patients should be regularly evaluated for GI symptoms during their course of treatment.

Criteria for Discontinuation:

The drug should be discontinued if significant liver injury occurs. (4, 5, 6)

References

1- Vumerity (diroximel fumarate) delayed-release capsules prescribing information.https://www.accessdata.fda.gov/drugsatfdadocs/label/2019/ 211855s000lbl.pdf (Accessed on May 04, 2020).

2-Muñoz MA, Kulick CG, Kortepeter CM, et al. Liver injury associated with dimethyl fumarate in multiple sclerosis patients. Mult Scler 2017:1352458516688351.

3-Rosenkranz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med 2015; 372:1476.

4-Naismith RT, Wundes A, Ziemssen T, et al. Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study. CNS Drugs 2020; 34:185.

5-Xu Z, Zhang F, Sun F, et al. Dimethyl fumarate for multiple sclerosis.

Cochrane Database Syst Rev 2015; :CD011076.

6- Bafiertam (monomethyl fumarate) delayed-release capsules, prescribing information.https://www.accessdata.fda.gov/drugsatfda_docs/label/ 2020/210296s000lbl.pdf (Accessed on May 06, 2020).