Gilenya (fingolimod; Novartis)

Approved 9/1/10

How it works:

Fingolimod is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in MS is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

Things to look out for:

  • Reduction in heart rate
  • AV blocks
  • Risk of infections
  • Macular edema
  • Respiratory effects
  • Liver enzyme elevations
  • Elevated blood pressure

QUIZ: TEST YOUR KNOWLEDGE OF MS THERAPY AT THE END OF ARTICLE 

Use in Special Populations:

  • Pregnancy: Category C. No adequate and well-controlled studies in pregnant women. There is a registry that monitors pregnancy outcomes in women exposed to Gilenya during pregnancy.  Encourage patients to enroll by calling (877) 598-7237.
  • Nursing mothers: It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug.
  • Children: Safety and effectiveness in pediatric patients below the age of 18 years have not been established.
  • Elderly: Clinical studies did not include sufficient numbers of patients ³65yrs old to determine whether they respond differently. Use with caution.
  • Renal impairment: The blood level of metabolites is increased (up to 13-fold) in patients with severe renal impairment, however, the toxicity of these metabolites has not been fully explored. Blood levels of these metabolites in patients with mild to moderate impairment have not been assessed.
  • Hepatic impairment: Patients with severe hepatic impairment should be closely monitored, as the risk of adverse reactions may be greater. No adjustments are needed for patients with mild to moderate impairment.

What to tell your patients:

  • A transient decrease in heart rate can occur when initiating therapy. Patients will need to be observed in the doctor’s office or other facility for at least 6 hours after the first dose; also on treatment re-initiation.
  • Patients may be more likely to be at risk for infections. Live vaccines should be avoided during treatment and for 2 months after discontinuation. Advise patients who have not had chickenpox or vaccination to consider VZV vaccination prior to commencing treatment.
  • Patients should report any changes in vision.
  • New onset or worsening of dyspnea should be reported.
  • May increase liver enzymes.
  • Effective contraception should be used during and for two months after stopping therapy.
  • Gilenya may remain in the blood and continue to have effects, including decreased blood lymphocyte counts, for up to 2 months following the last dose.

Tecfidera (dimethyl fumarate; Biogen Idec)

 Approved 3/27/13; available soon

How it works:

The mechanism of action is unknown but dimethyl fumarate (DMF) and the metabolite monomethyl fumarate (MMF) have been shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans. The Nrf2 pathway is involved in the cellular response to oxidative stress. MMF has been identified as a nicotinic acid receptor agonist in vitro.

Use in Special Populations:

  • Pregnancy: Category C. No adequate and well-controlled studies in pregnant women. There is a registry that monitors pregnancy outcomes in women exposed to Tecfidera during pregnancy.  Encourage patients to enroll by calling (800) 456-2255.
  • Nursing mothers: It is not known whether this drug is excreted in human milk. Caution should be exercised when administered to nursing women.
  • Children: Safety and effectiveness in pediatric patients have not been established.
  • Elderly: Clinical studies did not include sufficient numbers of patients ³65yrs old to determine whether they respond differently.
  • Renal impairment: No studies conducted, however the condition should not affect exposure. No dosage adjustment is necessary.
  • Hepatic impairment: No studies conducted, however the condition should not affect exposure. No dosage adjustment is necessary.

Things to look out for:

  • Lymphopenia
  • Flushing

What to tell your patients:

  • Patients will be provided with two strengths of Tecfidera when starting treatment: 120mg capsules for the 7 day starter dose and 240mg capsules for the maintenance dose, both to be taken twice daily.
  • Flushing and GI reactions are the most common reactions, especially at the initiation of therapy, and may decrease over time.
  • A recent blood test (within 6 months) should be available before starting therapy to identify patients with pre-existing low lymphocyte counts. Blood tests are recommended annually, and as clinically indicated.

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