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.
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.
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.
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).
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is contraindicated (has not been studied).
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.
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, drug reaction with eosinophilia and systemic symptoms, hypersensitivity reaction
Respiratory: Interstitial lung disease (including acute interstitial pneumonitis), pulmonary hypertension
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
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.
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
Yes
Tablets (Aubagio Oral)
7 mg (per each): $381.31
14 mg (per each): $381.31
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Aubagio: 14 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 14 mg
Administer without regard to meals.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
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.
Multiple sclerosis, relapsing: Treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.
Substrate of BCRP; Inhibits BCRP, CYP2C8 (Moderate), OAT1/3, OATP1B1/1B3; Induces CYP1A2 (Moderate);
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Alpelisib: BCRP/ABCG2 Inhibitors may increase 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 serum concentration of Amodiaquine. Risk X: Avoid
Anagrelide: CYP1A2 Inducers (Moderate) may decrease serum concentration of Anagrelide. CYP1A2 Inducers (Moderate) may decrease active metabolite exposure of Anagrelide. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase 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
Atrasentan: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atrasentan. Risk X: Avoid
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Teriflunomide may increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Bendamustine: CYP1A2 Inducers (Moderate) may decrease 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
Bile Acid Sequestrants: May decrease 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 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 increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Caffeine and Caffeine Containing Products: CYP1A2 Inducers (Moderate) may decrease serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Charcoal, Activated: May decrease 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 increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofarabine: OAT1/3 Inhibitors may increase serum concentration of Clofarabine. Risk C: Monitor
ClomiPRAMINE: CYP1A2 Inducers (Moderate) may decrease serum concentration of ClomiPRAMINE. Risk C: Monitor
CloZAPine: CYP1A2 Inducers (Moderate) may decrease serum concentration of CloZAPine. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Dabrafenib: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Dabrafenib. Risk C: Monitor
Daprodustat: CYP2C8 Inhibitors (Moderate) may increase 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 serum concentration of Dasabuvir. Risk C: Monitor
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects 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 serum concentration of Desloratadine. Risk C: Monitor
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
DULoxetine: CYP1A2 Inducers (Moderate) may decrease serum concentration of DULoxetine. Risk C: Monitor
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix. Risk X: Avoid
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase 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 concentration of Enzalutamide. CYP2C8 Inhibitors (Moderate) may increase active metabolite exposure of Enzalutamide. Risk C: Monitor
Erlotinib: CYP1A2 Inducers (Moderate) may decrease 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 increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects 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 increase adverse/toxic effects of Teriflunomide. Risk X: Avoid
Lidocaine (Systemic): CYP1A2 Inducers (Moderate) may decrease serum concentration of Lidocaine (Systemic). Risk C: Monitor
Melatonin: CYP1A2 Inducers (Moderate) may decrease serum concentration of Melatonin. Risk C: Monitor
Mexiletine: CYP1A2 Inducers (Moderate) may decrease serum concentration of Mexiletine. Risk C: Monitor
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Momelotinib. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
OAT1/3 Substrates (Clinically Relevant): Teriflunomide may increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Teriflunomide may increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
OLANZapine: CYP1A2 Inducers (Moderate) may decrease serum concentration of OLANZapine. Risk C: Monitor
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of the dasabuvir component may be increased. Risk C: Monitor
Ozanimod: CYP2C8 Inhibitors (Moderate) may increase active metabolite exposure of Ozanimod. Risk C: Monitor
PACLitaxel (Conventional): CYP2C8 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP2C8 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
PAZOPanib: BCRP/ABCG2 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Pioglitazone: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Pioglitazone. Risk C: Monitor
Pirfenidone: CYP1A2 Inducers (Moderate) may decrease serum concentration of Pirfenidone. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of 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 serum concentration of Pomalidomide. Risk C: Monitor
Propranolol: CYP1A2 Inducers (Moderate) may decrease serum concentration of Propranolol. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects 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 serum concentration of Repaglinide. Risk C: Monitor
Resmetirom: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Resmetirom. Risk X: Avoid
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase active metabolite exposure of Revefenacin. Risk X: Avoid
Riluzole: CYP1A2 Inducers (Moderate) may decrease serum concentration of Riluzole. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
ROPINIRole: CYP1A2 Inducers (Moderate) may decrease serum concentration of ROPINIRole. Risk C: Monitor
Rosuvastatin: Teriflunomide may increase 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 increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Seladelpar: OAT1/3 Inhibitors may increase serum concentration of Seladelpar. Risk X: Avoid
Selexipag: CYP2C8 Inhibitors (Moderate) may increase active metabolite exposure 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 decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Sulopenem Etzadroxil: OAT1/3 Inhibitors may increase serum concentration of Sulopenem Etzadroxil. Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects 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
Tasimelteon: CYP1A2 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Taurursodiol. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Theophylline Derivatives: CYP1A2 Inducers (Moderate) may decrease serum concentration of Theophylline Derivatives. Risk C: Monitor
TiZANidine: CYP1A2 Inducers (Moderate) may decrease serum concentration of TiZANidine. Risk C: Monitor
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Tovorafenib: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Tovorafenib. Risk X: Avoid
Treprostinil: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Treprostinil. Risk C: Monitor
Tucatinib: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Tucatinib. Risk C: Monitor
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: BCRP/ABCG2 Inhibitors may increase 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 (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider Therapy Modification
Vadadustat: OAT1/3 Inhibitors may increase serum concentration of Vadadustat. Risk C: Monitor
Vorasidenib: CYP1A2 Inducers (Moderate) may decrease serum concentration of Vorasidenib. Risk X: Avoid
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Voxilaprevir. Risk X: Avoid
Warfarin: Teriflunomide may increase anticoagulant effects of Warfarin. Teriflunomide may decrease anticoagulant effects of Warfarin. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Zavegepant. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
[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]).
[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 or within 2 years after discontinuation of teriflunomide in the pregnancy registry (800-745-4447, option 2).
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).
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.
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.
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%)
Sex: There was a 23% decrease in Cl in females compared with males.