What is the recommended starting dose for dimethyl fumarate (DMF) initiation?

Recommended Starting Dose for Dimethyl Fumarate (DMF) Initiation

The starting dose for dimethyl fumarate is 120 mg twice a day orally for 7 days, followed by increasing to the maintenance dose of 240 mg twice a day orally. 1

Dosing Schedule and Administration

• The FDA-approved dosing regimen begins with 120 mg twice daily for 7 days, then increases to the maintenance dose of 240 mg twice daily 1
• Dimethyl fumarate delayed-release capsules should be swallowed whole and intact - they should not be crushed, chewed, or sprinkled on food 1
• The medication can be taken with or without food, though administration with food may reduce the incidence of flushing 1
• For patients who do not tolerate the maintenance dose, temporary dose reductions to 120 mg twice daily may be considered, but the recommended maintenance dose should be resumed within 4 weeks 1
• If patients cannot tolerate returning to the maintenance dose, discontinuation of dimethyl fumarate should be considered 1

Managing Common Side Effects

• Gastrointestinal symptoms (abdominal cramps, nausea, diarrhea) are common adverse effects, occurring in over two-thirds of patients 2
• These GI effects can be mitigated by initiating therapy at a low dose and gradually increasing as recommended 2
• Flushing occurs in approximately one-third of patients and tends to subside with ongoing therapy 2
• Administration of non-enteric coated aspirin (up to 325 mg) 30 minutes prior to dimethyl fumarate dosing may reduce the incidence or severity of flushing 1

Required Baseline Testing

• Complete blood cell count (CBC) including lymphocyte count should be obtained before initiation of therapy 1
• Serum aminotransferase, alkaline phosphatase, and total bilirubin levels should be checked prior to treatment 1
• Additional baseline testing should include urinalysis and serum chemistry profile to establish renal function 3

Monitoring Requirements

• Laboratory monitoring should follow this schedule:
  • Serum chemistry and urinalysis: every 2 weeks for the first month, monthly for the first 6 months, and bimonthly thereafter 2, 3
  • CBC and platelet counts: every other week for the first 2 months, monthly until 6 months, and bimonthly thereafter 2

Special Considerations

• Lymphopenia and leukopenia are uncommon adverse events but significantly associated with dimethyl fumarate therapy 4
• Serious but reversible renal side effects have been sporadically reported 2
• Long-term safety data from the ENDORSE study showed sustained efficacy and safety in patients followed for up to 13 years 5
• Dimethyl fumarate should be administered only by directly observed therapy and with case management strategies to ensure adherence 2

Alternative Dosing Approaches

• Some research suggests that a simplified twice-daily DMF dosing regimen (rather than three times daily as used in some European formulations) may be well-tolerated while providing similar efficacy 6
• This approach allows patients to reach higher doses more quickly while maintaining a simpler dosing schedule 6

By following these dosing guidelines and monitoring protocols, clinicians can optimize the safety and efficacy of dimethyl fumarate therapy while minimizing adverse effects.