Teriflunomide

Cases of serious skin reactions, including cases of Stevens-Johnson syndrome and fatal toxic epidermal necrolysis have been reported with teriflunomide; very rare cases of drug reaction with eosinophilia and systemic symptoms have been reported with leflunomide. Discontinue if evidence of severe dermatologic reactions occurs and begin an accelerated drug elimination procedure (eg, cholestyramine, activated charcoal) immediately; in such cases, patients should not be re-exposed to teriflunomide.

Use of leflunomide has been associated with reports of hepatotoxicity, hepatic failure, and death, therefore, a similar risk is expected with teriflunomide. Patients with preexisting liver disease (acute or chronic liver disease or ALT >2 x ULN) may be at an increased risk of developing elevated transaminases during therapy; use is contraindicated in patients with severe impairment. Use in patients with concurrent exposure to potentially hepatotoxic drugs may increase the risk of hepatotoxicity. Obtain transaminase and bilirubin levels within 6 months prior to initiation of treatment. Monitor ALT levels at least monthly for first 6 months during therapy; if hepatotoxicity is likely teriflunomide-induced, start drug elimination procedures (eg, cholestyramine, activated charcoal) and monitor liver function tests weekly until normalized. Discontinuation of therapy may be considered if transaminases increase >3 x ULN.

Anaphylaxis and severe allergic reactions may occur; discontinue if any signs or symptoms of hypersensitivity reaction occur and begin an accelerated drug elimination procedure (eg, cholestyramine, activated charcoal) immediately; in such cases, patients should not be re-exposed to teriflunomide.

Increases in blood pressure have been reported; monitor at initiation of therapy and periodically thereafter.

May increase susceptibility to infection, including opportunistic pathogens. Severe infections, sepsis, and fatalities have been reported with leflunomide. One case of fatal sepsis has been reported with teriflunomide. Not recommended in patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely; consider suspension or discontinuation of therapy and drug elimination procedures (eg, cholestyramine, activated charcoal) if infection is serious.

Interstitial lung disease, including acute interstitial pneumonitis, has been reported; may be fatal and occur at any time during therapy. Consider treatment discontinuation in patients who develop new onset or worsening of pulmonary symptoms. Drug elimination procedures (eg, cholestyramine, activated charcoal) should be considered if evidence of interstitial lung disease.

Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials with use of some immunosuppressive medications.

Very rare cases of pancreatitis have been reported (Aubagio Canadian product monograph 2015); discontinue therapy in patients with symptoms of acute pancreatitis suspected to be drug-induced and begin drug elimination procedures (eg, cholestyramine, activated charcoal).

Cases of peripheral neuropathy (including polyneuropathy and mononeuropathy) have been reported; use with caution in patients >60 years, receiving concomitant neurotoxic medications or patients with diabetes; discontinue if evidence of peripheral neuropathy occurs and begin drug elimination procedures (eg, cholestyramine, activated charcoal).

Transient acute renal failure, most likely due to acute uric acid nephropathy, has been reported. Disease-related concerns:

Use with caution in patients with a prior history of significant hematologic abnormalities; avoid use with bone marrow dysplasia. Neutropenia, leukopenia, and thrombocytopenia (including rare cases of platelet counts 3) have been reported in clinical trials. Use of leflunomide has been associated with rare pancytopenia, agranulocytosis, and thrombocytopenia, therefore, a similar risk may be expected with teriflunomide. Monitoring of hematologic function is required.

Safety has not been established in patients with latent tuberculosis infection. Patients should be screened for tuberculosis and if necessary, treated prior to initiating therapy. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

If coadministered with other potential immunosuppressive agents or switching from teriflunomide to another known immunosuppressant, increased monitoring for hematological adverse effects is necessary. Special populations:

Based on animal data, teriflunomide may cause major birth defects if used in pregnant women. Teriflunomide is contraindicated in pregnant women or women of childbearing potential who are not using effective contraception. Pregnancy must be avoided during therapy or prior to completing the accelerated elimination treatment protocol. Other warnings/precautions:

Due to variations in clearance, it may take up to 2 years to reach low levels of teriflunomide metabolite serum concentrations. A drug elimination procedure using cholestyramine or activated charcoal is recommended when a more rapid elimination is needed. If a response to teriflunomide had already been observed, the use of a rapid elimination procedure may result in the return of disease activity.

Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there are no data available concerning secondary transmission of live vaccines in patients receiving therapy.