Medically reviewed on March 25, 2018.
(ter i FLOO noh mide)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aubagio: 7 mg
Aubagio: 14 mg [contains corn starch, fd&c blue #2 aluminum lake]
Brand Names: U.S.
- Pyrimidine Synthesis Inhibitor
Teriflunomide is an immunomodulatory agent that inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects. It may reduce the number of activated lymphocytes in the CNS.
Vd: IV: 11 L
Primarily by hydrolysis to minor metabolites; secondary pathways include oxidation, conjugation, and N-acetylation
Feces (~38%); urine (~23%)
Time to Peak
Plasma: 1-4 hours
Median: 18-19 days; enterohepatic recycling appears to contribute to the long half-life of this agent, since activated charcoal and cholestyramine substantially reduce plasma half-life
Special Populations: Gender
There was a 23% decrease in Cl in females compared with males.
Use: Labeled Indications
Multiple sclerosis: Treatment of patients with relapsing forms of multiple sclerosis.
Hypersensitivity to teriflunomide, leflunomide, or any component of the formulation; severe hepatic impairment; coadministration with leflunomide; pregnant women and females of reproductive potential not using effective contraception; pregnancy
Canadian labeling: Additional contraindications (not in US labeling): Immunodeficiency states (eg, AIDS); impaired bone marrow function or significant anemias, leucopenia, neutropenia, or thrombocytopenia; serious active infections
Multiple sclerosis: Adults: Oral: 7 mg or 14 mg once daily
Dosing: Renal Impairment
Mild, moderate, or severe impairment: No dosage adjustment necessary.
Severe impairment requiring dialysis: Data from a small pharmacokinetic study (n=5) suggest that hemodialysis removes a negligible amount of teriflunomide (Bergner 2013).
Dosing: Hepatic Impairment
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is contraindicated (has not been studied).
Dosing: Adjustment for Toxicity
ALT elevations >3 times ULN: Discontinue teriflunomide and initiate cholestyramine or activated charcoal to enhance elimination
Drug elimination procedure: To achieve nondetectable serum concentrations (<0.02 mg/L) of teriflunomide administer either of the following:
Cholestyramine: 8 g every 8 hours for 11 days. If not tolerated, may decrease to 4 g every 8 hours for 11 days. The 11 days do not need to be consecutive unless plasma concentrations need to be lowered rapidly.
Activated charcoal: 50 g every 12 hours for 11 days. The 11 days do not need to be consecutive unless plasma concentrations need to be lowered rapidly.
Note: Both treatments have successfully lead to >98% decrease in teriflunomide concentrations.
Administer without regard to meals.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Amodiaquine: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Amodiaquine. Avoid combination
Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCRP/ABCG2 Substrates: Teriflunomide may increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy
Bendamustine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Bendamustine. Concentrations of active metabolites may be increased. Monitor therapy
Bile Acid Sequestrants: May decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is unlikely to be effective at avoiding the interaction. Consider therapy modification
Caffeine and Caffeine Containing Products: Teriflunomide may decrease the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy
Charcoal, Activated: May decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to charcoal when possible. Separating drug administration is not likely to be effective at avoiding this interaction. Consider therapy modification
CloZAPine: CYP1A2 Inducers may decrease the serum concentration of CloZAPine. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
CYP1A2 Substrates (High risk with Inducers): Teriflunomide may decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy
CYP2C8 Substrates (High risk with Inhibitors): CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors). Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Erlotinib: Teriflunomide may decrease the serum concentration of Erlotinib. Management: Avoid the concomitant use of erlotinib and teriflunomide if possible. If concomitant use is unavoidable, increase the erlotinib dose by 50 mg increments at 2-week intervals to a maximum of 300 mg. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Grazoprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination
Leflunomide: May enhance the adverse/toxic effect of Teriflunomide. Leflunomide may increase the serum concentration of Teriflunomide. Avoid combination
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
OAT3 Substrates: Teriflunomide may increase the serum concentration of OAT3 Substrates. Monitor therapy
OATP1B1/SLCO1B1 Substrates: Teriflunomide may increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Pirfenidone: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Pirfenidone. Monitor therapy
Repaglinide: Teriflunomide may increase the serum concentration of Repaglinide. Monitor therapy
Riluzole: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Riluzole. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Rosuvastatin: Teriflunomide may increase the serum concentration of Rosuvastatin. Management: Limit the maximum adult rosuvastatin dose to 10 mg/day in patients receiving teriflunomide, and monitor for evidence of rosuvastatin toxicity (eg, muscle toxicity, elevated transaminase concentrations). Consider therapy modification
Selexipag: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Selexipag. Management: If initiating selexipag in a patient on a moderate CYP2C8 inhibitor, consider a less frequent dosing regimen (ie, once daily). If initiating a moderate CYP2C8 inhibitor in a patient on selexipag, consider a selexipag dose reduction. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Voxilaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination
Warfarin: Teriflunomide may decrease the serum concentration of Warfarin. Monitor therapy
Central nervous system: Headache (16% to 18%)
Dermatologic: Alopecia (10% to 13%)
Endocrine & metabolic: Hypophosphatemia (4% to 18%)
Gastrointestinal: Diarrhea (13% to 14%), nausea (8% to 11%)
Hematologic & oncologic: Neutropenia (4% to 16%)
Hepatic: Increased serum ALT (6% to 15%)
1% to 10%:
Cardiovascular: Hypertension (3% to 4%)
Central nervous system: Paresthesia (8% to 9%)
Endocrine & metabolic: Hyperkalemia (1%)
Neuromuscular & skeletal: Arthralgia (6% to 8%), peripheral neuropathy (including carpal tunnel syndrome; 1% to 2%)
Renal: Renal failure (transient; 1%)
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, cytomegalovirus disease (reactivation), hypersensitivity reaction, increased serum creatinine, interstitial pulmonary disease, jaundice, pancreatitis, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
Concerns related to adverse effects:
• Dermatologic reactions: 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.
• Hepatotoxicity: [US Boxed Warning]: 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.
• Hypersensitivity reactions: 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.
• Hypertension: Increases in blood pressure have been reported; monitor at initiation of therapy and periodically thereafter.
• Infections: 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: 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.
• Malignancy: 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.
• Pancreatitis: 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).
• Peripheral neuropathy: 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).
• Renal effects: Transient acute renal failure, most likely due to acute uric acid nephropathy, has been reported.
• Hematologic disorders: 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 <50,000/mm3) 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.
• Tuberculosis: 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:
• Drug-drug interactions: 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.
• Immunosuppressants: If coadministered with other potential immunosuppressive agents or switching from teriflunomide to another known immunosuppressant, increased monitoring for hematological adverse effects is necessary.
• Pregnancy/women of childbearing potential: [US Boxed Warning]: 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.
• Drug elimination procedure: 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.
• Immunizations: 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.
CBC within 6 months of initiation and periodically thereafter based on signs/symptoms of infection; serum creatinine; serum transaminase and bilirubin within 6 months of initiation of therapy and monthly during the initial 6 months of treatment. In addition, monitor for signs/symptoms of severe infection, abnormalities in hepatic function tests, symptoms of hepatotoxicity, and blood pressure (baseline and periodically thereafter). Monitor hepatic function tests weekly until normalized in patients with suspected teriflunomide-induced hepatotoxicity. Screen for tuberculosis and pregnancy prior to therapy.
[US Boxed Warning]: 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. Pregnancy must be excluded prior to initiating treatment. Women of childbearing potential should not receive therapy until pregnancy has been excluded, they have been counseled concerning fetal risk, and reliable contraceptive measures have been confirmed. Following treatment, pregnancy should be avoided until undetectable serum concentrations (<0.02 mg/L) are verified. This may be accomplished by the use of an enhanced drug elimination procedure using cholestyramine or activated charcoal powder. If pregnancy occurs during treatment, discontinue therapy and initiate the accelerated elimination procedure.
Teriflunomide is also found in semen. Males and their female partners should use reliable contraception during therapy. Males taking teriflunomide who wish to father a child should consider discontinuing therapy and using the accelerated elimination procedure to decrease the potential risk of fetal exposure. (Note: Without use of the accelerated elimination procedure, teriflunomide may remain in the serum for up to 2 years).
Pregnant women exposed to teriflunomide should be registered with the pregnancy registry (800-745-4447, option 2).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, diarrhea, hair thinning or loss, or joint pain. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe headache, severe dizziness, passing out, vision changes, shortness of breath, bruising, bleeding, severe loss of strength and energy, swollen glands, burning or numbness feeling, signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), or signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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- Drug class: selective immunosuppressants
Other brands: Aubagio