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Teriflunomide: Drug information

Teriflunomide: Drug information
(For additional information see "Teriflunomide: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hepatotoxicity:

Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting. Concomitant use of teriflunomide with other hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide therapy. Monitor ALT levels at least monthly for 6 months after starting teriflunomide. If drug-induced liver injury is suspected, discontinue teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal. Teriflunomide is contraindicated in patients with severe hepatic impairment. Patients with preexisting liver disease may be at an increased risk of developing elevated serum transaminases when taking teriflunomide.

Embryofetal toxicity:

Teriflunomide is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with teriflunomide in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide treatment and during an accelerated drug elimination procedure after teriflunomide treatment. Stop teriflunomide and use an accelerated drug elimination procedure if the patient becomes pregnant.

Brand Names: US
  • Aubagio
Brand Names: Canada
  • ACH-Teriflunomide;
  • APO-Teriflunomide;
  • Aubagio;
  • JAMP-Teriflunomide;
  • M-Teriflunomide;
  • MAR-Teriflunomide;
  • NAT-Teriflunomide;
  • PMS-Teriflunomide;
  • SANDOZ Teriflunomide;
  • TEVA-Teriflunomide
Pharmacologic Category
  • Pyrimidine Synthesis Inhibitor
Dosing: Adult
Multiple sclerosis, relapsing

Multiple sclerosis, relapsing: Note: In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other appropriate specialists (eg, liver specialists) regarding treatment options before initiating therapy (Ref).

Oral: 7 mg or 14 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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 (Ref).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is contraindicated (has not been studied).

Dosing: Adjustment for Toxicity: Adult

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.

or

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.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Alopecia (10% to 13%)

Endocrine & metabolic: Hypophosphatemia (18%)

Gastrointestinal: Diarrhea (13% to 14%), nausea (8% to 11%)

Hematologic & oncologic: Lymphocytopenia (10% to 12%)

Hepatic: Increased serum alanine aminotransferase (13% to 15%)

Nervous system: Headache (16% to 18%)

1% to 10%:

Cardiovascular: Hypertension (3% to 4%)

Hematologic & oncologic: Neutropenia (4% to 6%)

Nervous system: Paresthesia (8% to 9%), peripheral neuropathy (including carpal tunnel syndrome: 1% to 2%)

Neuromuscular & skeletal: Arthralgia (6% to 8%)

Frequency not defined:

Hepatic: Jaundice

Infection: Cytomegalovirus disease (reactivation)

Respiratory: Tuberculosis

Postmarketing:

Dermatologic: Exacerbation of psoriasis, nail disease (including nail psoriasis), psoriasis, pustular psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Gastrointestinal: Colitis, pancreatitis

Hematologic & oncologic: Thrombocytopenia

Hepatic: Acute hepatic failure, hepatic injury

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Immunologic: Drug reactions with eosinophilia and systemic symptoms

Respiratory: Interstitial pulmonary disease (including acute interstitial pneumonitis)

Contraindications

Hypersensitivity to teriflunomide, leflunomide, or any component of the formulation; severe hepatic impairment; coadministration with leflunomide; pregnant women; females of reproductive potential not using effective contraception.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic reactions: Cases of serious, sometimes fatal, skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms, have been reported with teriflunomide. 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]: Postmarketing cases of clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, have been reported in patients treated with teriflunomide and may occur at any time during therapy. 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 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. In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). 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); 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.

Disease-related concerns:

• 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 tuberculosis (TB) infection (latent TB). Patients should be screened for TB and if necessary, treated prior to initiating therapy.

Special populations:

• Pregnancy/women of childbearing potential: [US Boxed Warning]: Teriflunomide is contraindicated in pregnant women or women of childbearing potential who are not using effective contraception. Pregnancy must be excluded prior to initiating treatment in females of reproductive potential.

Other warnings/precautions:

• 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. Avoid live-attenuated vaccines in patients who currently receive or have recently discontinued teriflunomide; consider using live-attenuated vaccines only if risk of infection is high and killed vaccines are unavailable (AAN [Farez 2019]). There are no data available concerning secondary transmission of live vaccines in patients receiving therapy.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Aubagio: 7 mg, 14 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]

Generic: 7 mg, 14 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Aubagio Oral)

7 mg (per each): $373.83

14 mg (per each): $373.83

Tablets (Teriflunomide Oral)

7 mg (per each): $10.42 - $343.13

14 mg (per each): $10.42 - $343.13

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Aubagio: 14 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Generic: 14 mg

Administration: Adult

Administer without regard to meals.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202992s013s015lbl.pdf#page=25 must be dispensed with this medication.

Use: Labeled Indications

Multiple sclerosis, relapsing: Treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2; Inhibits BCRP/ABCG2, CYP2C8 (moderate), OAT1/3, OATP1B1/1B3 (SLCO1B1/1B3); Induces CYP1A2 (moderate)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification

Amodiaquine: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Amodiaquine. Risk X: Avoid combination

Anagrelide: CYP1A2 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inducers (Moderate) may decrease the serum concentration of Anagrelide. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Teriflunomide may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Bendamustine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Bendamustine. Concentrations of active metabolites may be increased. Management: Consider alternatives to moderate CYP1A2 inducers during therapy with bendamustine due to the potential for decreased bendamustine plasma concentrations and reduced efficacy. Risk D: Consider therapy modification

Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Caffeine and Caffeine Containing Products: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Caffeine and Caffeine Containing Products. Risk C: 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. Risk D: Consider therapy modification

Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

ClomiPRAMINE: CYP1A2 Inducers (Moderate) may decrease the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

CloZAPine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Dabrafenib: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Dabrafenib. Risk C: Monitor therapy

Daprodustat: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Daprodustat. Management: Reduce the daprodustat starting dose by half if combined with moderate CYP2C8 inhibitors, unless the dose is 1 mg, then no dose adjustment is required. Monitor hemoglobin and adjust daprodustat dose when starting or stopping moderate CYP2C8 inhibitors. Risk D: Consider therapy modification

Dasabuvir: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Dasabuvir. Risk C: Monitor therapy

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification

Desloratadine: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Desloratadine. Risk C: Monitor therapy

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

DULoxetine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of DULoxetine. Risk C: Monitor therapy

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination

Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification

Enzalutamide: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy

Erlotinib: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Erlotinib. Management: Avoid the concomitant use of erlotinib and moderate CYP1A2 inducers 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. Risk D: Consider therapy modification

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: May enhance the adverse/toxic effect of Teriflunomide. Risk X: Avoid combination

Lidocaine (Systemic): CYP1A2 Inducers (Moderate) may decrease the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Melatonin: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Melatonin. Risk C: Monitor therapy

Mexiletine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Mexiletine. Risk C: Monitor therapy

Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

OAT1/3 Substrates (Clinically Relevant): Teriflunomide may increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Teriflunomide may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

OLANZapine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of OLANZapine. Risk C: Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of the dasabuvir component may be increased. Risk C: Monitor therapy

Ozanimod: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Ozanimod. Risk C: Monitor therapy

PACLitaxel (Conventional): CYP2C8 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP2C8 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pioglitazone: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Pioglitazone. Risk C: Monitor therapy

Pirfenidone: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Pirfenidone. Risk C: Monitor therapy

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Pomalidomide: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Pomalidomide. Risk C: Monitor therapy

Propranolol: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Propranolol. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Repaglinide: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination

Riluzole: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Riluzole. Risk C: Monitor therapy

Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

ROPINIRole: CYP1A2 Inducers (Moderate) may decrease the serum concentration of ROPINIRole. Risk C: Monitor therapy

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). Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Selexipag: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Selexipag. Management: Reduce the selexipag dose to once daily when combined with moderate CYP2C8 inhibitors. Revert back to twice daily selexipag dosing upon stopping the moderate CYP2C8 inhibitor. Risk D: Consider therapy modification

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tasimelteon: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy

Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Theophylline Derivatives: CYP1A2 Inducers (Moderate) may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inducers (Moderate) may decrease the serum concentration of TiZANidine. Risk C: Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Treprostinil: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Treprostinil. Risk C: Monitor therapy

Tucatinib: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Tucatinib. Risk C: Monitor therapy

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination

Warfarin: Teriflunomide may enhance the anticoagulant effect of Warfarin. Teriflunomide may diminish the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination

Reproductive Considerations

[US Boxed Warning]: Teriflunomide is contraindicated in females of reproductive potential who are not using effective contraception. Exclude pregnancy before the start of treatment with teriflunomide in females of reproductive potential. 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.

[US Boxed Warning]: Advise females of reproductive potential to use effective contraception during teriflunomide treatment and during an accelerated drug elimination procedure after teriflunomide treatment. Women who wish to become pregnant, as well as all females of reproductive potential, should undergo the accelerated drug elimination procedure when teriflunomide is discontinued. Pregnancy should be avoided until undetectable serum concentrations (<0.02 mg/L) are verified.

Teriflunomide is found in semen. Males and their female partners should use reliable contraception during therapy. Males who wish to father a child should discontinue teriflunomide and undergo the accelerated drug elimination procedure or wait until plasma teriflunomide concentrations are <0.02 mg/L.

In general, disease-modifying therapies for multiple sclerosis (MS) are stopped prior to a planned pregnancy except in females at high risk of MS activity (AAN [Rae-Grant 2018]). Consider use of agents other than teriflunomide for females at high risk of disease reactivation who are planning a pregnancy. Delaying pregnancy is recommended for females with persistent high disease activity; when disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).

Pregnancy Considerations

[US Boxed Warning]: Teriflunomide is contraindicated in pregnant women because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Stop teriflunomide and use an accelerated drug elimination procedure if the patient becomes pregnant. Pregnancy outcome information following maternal use during pregnancy or following use in male patients who fathered a child are limited (Andersen 2018; Kieseier 2014).

In general, disease-modifying therapies for multiple sclerosis (MS) are not initiated during pregnancy, except in females at high risk of MS activity (AAN [Rae-Grant 2018]). When disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).

Data collection to monitor pregnancy and infant outcomes following exposure to teriflunomide is ongoing. Health care providers are encouraged to enroll females exposed to teriflunomide during pregnancy in the pregnancy registry (800-745-4447, option 2).

Breastfeeding Considerations

It is not known if teriflunomide is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer. Other sources do not recommended breastfeeding (or to use with great caution) during therapy. The long half-life of teriflunomide should also be considered (Almas 2016; Dobson 2019; Fragoso 2018).

Monitoring Parameters

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, hypophosphatemia, and blood pressure (baseline and periodically thereafter). Monitor hepatic function tests weekly until normalized in patients with suspected teriflunomide-induced hepatotoxicity. Screen for tuberculosis prior to therapy; screen for other latent infections (eg, hepatitis) in high-risk populations (baseline). Evaluate pregnancy status in females of reproductive potential before treatment initiation.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: IV: 11 L

Protein binding: >99%

Metabolism: Primarily by hydrolysis to minor metabolites; secondary pathways include oxidation, conjugation, and N-acetylation

Half-life elimination: 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

Time to peak, plasma: 1-4 hours

Excretion: Feces (~38%); urine (~23%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Sex: There was a 23% decrease in Cl in females compared with males.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Aubagio;
  • (AR) Argentina: Aubagio | Flunisol | Funomid | Libinis | Tenomid | Terflimida;
  • (AT) Austria: Aubagio;
  • (AU) Australia: Apo teriflunomide | Aubagio | Pharmacor teriflunomide | Teriflagio | Teriflunomide gh | Teriflunomide sandoz | Terimide;
  • (BE) Belgium: Aubagio;
  • (BG) Bulgaria: Aubagio;
  • (BR) Brazil: Aubagio | Klamy | Ryfluna | Teriflunomida;
  • (CH) Switzerland: Aubagio;
  • (CL) Chile: Aubagio;
  • (CO) Colombia: Aubagio;
  • (CZ) Czech Republic: Aubagio;
  • (DE) Germany: Aubagio;
  • (DO) Dominican Republic: Aubagio;
  • (EC) Ecuador: Aubagio | Funomid;
  • (EE) Estonia: Aubagio;
  • (EG) Egypt: Aubagio;
  • (ES) Spain: Aubagio;
  • (FI) Finland: Aubagio;
  • (FR) France: Aubagio;
  • (GB) United Kingdom: Aubagio;
  • (GR) Greece: Aubagio;
  • (HK) Hong Kong: Aubagio;
  • (HR) Croatia: Aubagio;
  • (HU) Hungary: Aubagio;
  • (IE) Ireland: Aubagio;
  • (IN) India: Denopsy | Merosya | Scleteri | Terigen | Teru ms;
  • (IT) Italy: Aubagio;
  • (KR) Korea, Republic of: Aubagio;
  • (KW) Kuwait: Aubagio;
  • (LB) Lebanon: Aubagio;
  • (LT) Lithuania: Aubagio;
  • (LU) Luxembourg: Aubagio;
  • (LV) Latvia: Aubagio;
  • (MA) Morocco: Aubagio;
  • (MX) Mexico: Aubagio | Teriem;
  • (MY) Malaysia: Aubagio;
  • (NL) Netherlands: Aubagio;
  • (NO) Norway: Aubagio;
  • (NZ) New Zealand: Aubagio;
  • (PE) Peru: Aubagio;
  • (PL) Poland: Aubagio;
  • (PR) Puerto Rico: Aubagio;
  • (PT) Portugal: Aubagio;
  • (PY) Paraguay: Terflimida;
  • (QA) Qatar: Aubagio;
  • (RO) Romania: Aubagio;
  • (RU) Russian Federation: Abaggio | Aubagio | Femorix | Teriflunomide himrar;
  • (SA) Saudi Arabia: Aubagio;
  • (SE) Sweden: Aubagio;
  • (SG) Singapore: Aubagio;
  • (SI) Slovenia: Aubagio;
  • (SK) Slovakia: Aubagio;
  • (TH) Thailand: Aubagio;
  • (TN) Tunisia: Aubagio;
  • (TR) Turkey: Aubagio | Teflimes | Terigio;
  • (TW) Taiwan: Aubagio;
  • (UA) Ukraine: Aubagio;
  • (ZA) South Africa: Aubagio | Aubamide | Teriflunomide accord | Teriflunomide teva
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  3. Andersen JB, Moberg JY, Spelman T, Magyari M. Pregnancy outcomes in men and women treated with teriflunomide. A population-based nationwide Danish register study. Front Immunol. 2018;9:2706. doi:10.3389/fimmu.2018.02706 [PubMed 30532753]
  4. Aubagio (teriflunomide) [prescribing information]. Cambridge, MA: Genzyme Corporation; December 2022.
  5. Aubagio (teriflunomide) [prescribing information]. Cambridge, MA: Genzyme Corporation; November 2020.
  6. Aubagio (teriflunomide) [product monograph]. Mississauga, Ontario, Canada: Sanofi Genzyme; June 2023.
  7. Bergner R, Peters L, Schmitt V, et al. Leflunomide in dialysis patients with rheumatoid arthritis-a pharmacokinetic study. Clin Rheumatol. 2013;32(2):267-270. [PubMed 23179005]
  8. Dobson R, Dassan P, Roberts M, Giovannoni G, Nelson-Piercy C, Brex PA. UK consensus on pregnancy in multiple sclerosis: 'Association of British Neurologists' guidelines. Pract Neurol. 2019;19(2):106-114. doi: 10.1136/practneurol-2018-002060. [PubMed 30612100]
  9. Farez MF, Correale J, Armstrong MJ, et al. Practice guideline update summary: vaccine-preventable infections and immunization in multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2019;93(13):584-594. doi:10.1212/WNL.0000000000008157 [PubMed 31462584]
  10. Fragoso YD, Adoni T, Brooks JBB, et al. Practical evidence-based recommendations for patients with multiple sclerosis who want to have children. Neurol Ther. 2018;7(2):207-232. doi: 10.1007/s40120-018-0110-3. [PubMed 30167914]
  11. Kieseier BC, Benamor M. Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis. Neurol Ther. 2014;3(2):133-138. doi: 10.1007/s40120-014-0020-y. [PubMed 26000229]
  12. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis [published correction appears in Eur J Neurol. 2018;25(3):605]. Eur J Neurol. 2018;25(2):215-237. doi: 10.1111/ene.13536. [PubMed 29352526]
  13. O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293-1303. [PubMed 21991951]
  14. Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline: disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. https://download.lww.com/wolterskluwer_vitalstream_com/PermaLink/WNL/A/WNL_2018_04_19_RAEGRANT_NEUROLOGY2017835181R1_SDC3.pdf. Published April 2018. Accessed January 29, 2019.
  15. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
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