Tecfidera

Dimethyl Fumarate

THERAPY

Coverage

Protocols

Before Initiation of Therapy :

  • CBC, liver enzymes,total bilirubin, TSH, urinalysis, urinary albumin, creatinine ratio, JCV index
  • HBsAg, anti-HBc, anti-HBs, Hepatits C, HIV, VZV serology, Measles IgG
  • Vaccination status verified and updated if necessary
  • Pneumococcus and Haemophilus Influenza type B and VZV vaccines
  • Recent cerebral MRI (<3 months)
  • Chest Xray and /or Quantiferon

Monitoring During Therapy :

  • CBC, liver enzymes, creatinine, total bilirubin, Q2months x3 then Q6 months
  • Urinalysis Q. 6 months
  • If proteinuria de novo then do a urinary albumin to creatinine ratio and if abnormal a 24 hrs urine collection for protein and creatinine.
  • Annual cerebral MRI

Discontinue Therapy :

  • The half-life MMF, the active metabolite of DMF is 1 hour
  • The time for lymphocyte recovery is however several months

Studies

(Some studies only include abstracts)

Title

Confirm

Source

New England Journal of Medicine

Date Published

9/20/2012

Title

Define

Source

New England Journal of Medicine

Date Published

9/12/2012

Product Monograph

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Specific Concerns

PML :

PML has been diagnosed in patients receiving either Tecfidera for MS or Fumaderm for Psoriasis. Prolonged lymphopenia (lymphocyte count <0.5) appeared to be a risk factor for PML. In the MS placebo controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with Tecfidera then remained stable at this reduced level for the duration of treatment. Six percent (6%) of Tecfidera patients experienced lymphocyte counts < 0.5×109/L and remained so for the duration of treatment. Lymphocyte count begin to improve 4 weeks after stopping Tecfidera. The time to recovery to baseline however has not been established. PML has however been reported in fumarate treated patients without associated lymphopenia.

Contraindications :

  • Not recommended in patients with severe active gastrointestinal disorders or who are immunocompromised or have pre-existing lymphopenia.
  • ‍Live vaccines should not be administered while receiving Tecfidera or in the 6 weeks preceding the initiation of treatment.

Adverse Events :

  • ‍Cases of hypersensitivity, angioedema and anaphylactic reaction have been reported during the clinical trials and the post marketing period.
  • ‍Elevation of hepatic transaminases, proteinuria can be seen in the first 6 months of treatment.
  • ‍Flushing occurs in a third of patients. Gastrointestinal symptoms (i.e. diarrhea, nausea, abdominal pain) occurs in half of patients. Both can be reduced by taking Tecfidera during meals or with temporary dose reduction. ASA can reduce flushing. Severe flushing should alert the physician/nurse to possible anaphylactic reaction.

Recommended Dose and Dosage Adjustment :

Initial Dose

The starting dose for TECFIDERA is 120 mg twice a day orally, for a total of 240 mg per day.

Dosage Adjustment

After 7 days, increase to the recommended dose of 240 mg twice a day orally, for a total of 480 mg per day.

Additional Information

Temporary dose reduction to 120 mg twice a day (total of 240 mg per day) may reduce the occurrence of flushing and gastrointestinal (GI) side effects. Within one month, the recommended dose of 240 mg twice a day orally should be resumed.We however suggest to start at 120 mg once per day and increase by 120 mg per day every week up to the recommended dose of 240 mg twice a day. Slower increase in dosage appear to improve overall tolerability.