Authors

  1. Aschenbrenner, Diane S. MS, RN

Abstract

* Teriflunomide (Aubagio) has been approved to treat adults with relapsing multiple sclerosis.

 

* The drug label carries boxed warnings that teriflunomide can produce hepatotoxicity and that its use during pregnancy can cause birth defects.

 

 

Article Content

A new drug is now available to help treat adult patients with relapsing forms of multiple sclerosis. Teriflunomide (Aubagio), a pyrimidine synthesis inhibitor that has antiinflammatory effects, is an oral tablet given once daily. In clinical studies the annual relapse rate was significantly reduced with the use of teriflunomide. Although the exact mechanism of action isn't known, it's believed to be related to a reduction in the number of activated lymphocytes in the central nervous system. Teriflunomide has a long half-life-18 to 19 days-and takes about three months to reach steady state. The drug is eliminated primarily unchanged through the gastrointestinal tract, although some metabolites are also excreted in the urine.

 

Teriflunomide carries two boxed warnings and several nonboxed warnings on its label. One boxed warning is that teriflunomide can produce severe liver toxicity. The drug is contra-indicated in patients with severe hepatic impairment. Baseline transaminase and bilirubin levels should be obtained within the six months before therapy is started, and follow-up measurements should be taken at least monthly for six months. If a drug-induced liver injury is suspected, the drug should be discontinued and an accelerated-elimination procedure started. Options for such a procedure include the administration of the anticholesterol drug cholestyramine, 8 mg every eight hours for 11 days, or the administration of oral activated charcoal powder, 50 g every 12 hours for 11 days.

 

The second boxed warning is related to teratogenicity. Teriflunomide is a pregnancy category X drug, meaning that in animal studies the drug caused major birth defects when used during pregnancy. The birth defects that occurred in animals receiving teriflunomide included craniofacial and axial and appendicular skeletal defects; embryofetal deaths also occurred. Maternal toxicity from the drug wasn't present when these tera-togenetic effects occurred. Male-mediated fetal toxicity studies haven't been conducted. The drug is contraindicated in pregnant women, as well as in women of childbearing age unless they're using reliable birth control. Men taking teriflunomide should make sure that they and their partners use reliable contraception.

 

Other warnings and precautions include elevated risks of hypertension, a decrease in white blood cell count, peripheral neuropathy, acute renal failure and hyperkalemia, and (rarely) a severe skin reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. The most common adverse effects of teriflunomide are alopecia, diarrhea, influenza, nausea, paresthesia, and increases in alanine aminotransferase levels.

 

Nurses who prescribe or work with patients taking teriflunomide should confirm that the baseline liver-function studies (bilirubin and transaminase levels) have been performed and that levels are within normal ranges. Patient education should emphasize the importance of repeated blood work to assess liver function. The signs and symptoms of liver disease (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, or dark urine) should also be explained, as should the importance of reporting them at once to the prescriber. Nurses should confirm that the patient isn't pregnant at the time teriflunomide therapy is begun. They should include information on the importance of continuing effective birth control use while receiving the drug and during the washout period if the drug is discontinued. Breastfeeding should also be avoided. Because patients are at risk for infections secondary to a low white blood cell count, they should be carefully assessed for signs of infection. Patients should be instructed to report fever or other symptoms of infection. Nurses should monitor the patient's blood pressure throughout therapy. Because of the risk of serious adverse effects, all teriflunomide prescriptions come with a medication guide that provides the most current information about the drug's safety and gives guidance to patients on how they can help monitor themselves for serious adverse effects. Nurses should emphasize the importance of reading the entire medication guide each time a prescription is filled.

 

For the Food and Drug Administration news release regarding teriflunomide, as well as links to other resources, go to http://1.usa.gov/NoROVM.