THERAPEUTICS

Brands

• Aubagio

Generic?

• No

Class

• Immunomodulator

Commonly Prescribed for

(FDA approved in bold)

• Relapsing types of multiple sclerosis (MS)

• Rheumatoid arthritis

How the Drug Works

• Teriflunomide is the active metabolite of leflunomide. It inhibits dihydro-orotate dehydrogenase, a mitochondrial enzyme involved with pyrimidine biosynthesis, and disrupts interaction of T cells with antigenpresenting cells and reduces activated lymphocytes in the CNS

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, natalizumab, or fingolimod

Best Augmenting Combos for Partial Response or Treatment-Resistance

• May be as add-on therapy with β interferon

Tests

• Before starting obtain pregnancy test in all women of childbearing age. Check CBC, liver function tests, and renal function before starting treatment. Screen patients for latent tuberculosis infection with a tuberculin skin test. Perform monthly liver function tests for at least 6 months after starting treatment

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Increased rates of infection are common with all immune-modulating therapies. Hepatoxicity may be related to inhibition of dihydro-orotate dehydrogenase, a mitochondrial enzyme

Notable AEs

• Elevated liver transaminases, alopecia, diarrhea, influenza, nausea, increased blood pressure, hypophosphatemia (mild), and paresthesias

Life-Threatening or Dangerous AEs

• Hepatoxicity (as much as 5%) – fatal liver failure has been reported with leflunomide

• Neutropenia

• Peripheral neuropathy (1–2%, more common in elderly patients)

• Acute renal failure (1%)

• Hyperkalemia

• Stevens-Johnson syndrome and toxic epidermal necrolysis (rare)

• Worsening of preexisting interstitial lung disease

Weight Gain

• Unusual

Sedation

• Unusual

What to Do About AEs

• Severe leukopenia or thrombocytopenia is relatively uncommon but discontinue drug for rare events such as pancytopenia, agranulocytosis, or thrombocytopenia

• If severe infection develops consider discontinuing treatment and undergoing accelerated elimination procedure (outlined in pregnancy section)

• Avoid live vaccines while on treatment