THERAPEUTICS

Brands

• Gilenya

Generic?

• No

Class

• Immunomodulator

Commonly Prescribed for

(FDA approved in bold)

• Relapsing types of multiple sclerosis (MS)

• Amyotrophic lateral sclerosis (ALS)

• Heart failure and arrhythmia

• Prevention of rejection post-transplantation

How the Drug Works

• Modulates the sphingosine-1-phosphate receptor (S1PR), causing lymphocytes to sequester in lymph nodes. Sphingolipids and S1PR receptor are plentiful in the CNS and affect neurogenesis, neural cell function and migration. Fingolimod most likely acts at the S1PR1 receptor

• It may also stimulate glial cell repair and it may have cannabinoid receptor antagonism, and inhibit ceramide synthase

How Long Until It Works

• Typically takes months to determine clinical effects

If It Works

• May continue as long as needed for relapsing MS. Unclear if effective in progressive forms of MS

If It Doesn't Work

• May change to an alternative agent such as β- interferons, glatiramer acetate, or natalizumab

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Generally not used along with other diseasemodifying agents

Tests

• Before starting obtain CBC and liver function tests (within 6 months), ECG, ophthalmological examination, skin examination, and varicella serology. If varicella negative, give varicella zoster vaccination

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Sequestration of lymphocytes, as demonstrated by reduction in peripheral lymphocyte counts, likely explains the increased risk of infection. Release of sequestered lymphocytes after discontinuation may cause immediate clinical deterioration. The cause of cardiac events is unclear

Notable AEs

• Symptomatic bradycardia with initial dose, asymptomatic liver transaminase elevation, increased blood pressure, influenza, headache, back pain. These effects typically resolve in 6 hours or less

• Lymphocyte counts decreased to approximately 60% of baseline within 4–6 hours after the first dose and continue to decrease over a 2-week period to about 30% of baseline. CBC do not return to normal until 1–2 months

Life-Threatening or Dangerous AEs

• Varicella zoster infections, occasionally severe, after drug withdrawal

• Tumefactive MS lesions have been reported

• Dose-dependent reductions in forced expiratory volume