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Section 04 · Monograph

Teriflunomide

Reviewed Nov 2026FDA label
AubagioPyrimidine synthesis inhibitor
Forms
Tab: 7, 14mg
Dose
14mg once daily
MOA
Inhibits DHODH, ↓lymphocyte proliferation

Black Box Warning

  • Hepatotoxicity: severe liver injury including cases of fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis and is a prodrug of teriflunomide. Aubagio may cause similar hepatotoxicity; concomitant use with other hepatotoxic drugs may increase risk. Obtain transaminase and bilirubin levels within 6 months before initiation and monitor ALT at least monthly for 6 months after starting therapy
  • Do not initiate Aubagio in patients with severe hepatic impairment; discontinue Aubagio if drug-induced liver injury is suspected and start the accelerated elimination procedure
  • Teratogenicity/Risk of Fetal Death: based on animal data, Aubagio may cause major birth defects or fetal death if administered during pregnancy
  • Aubagio is contraindicated in women who are pregnant or who are of reproductive potential and not using effective contraception
  • Exclude pregnancy before starting Aubagio in females of reproductive potential; obtain a reliable negative pregnancy test result before initiation
  • Advise patients of reproductive potential to use effective contraception during treatment and during an accelerated elimination procedure after treatment
  • Stop Aubagio and use the accelerated elimination procedure if pregnancy occurs during treatment

Indications

  • Treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive diseaseFDA-labeled

Mechanism of Action

  • Inhibits dihydroorotate dehydrogenase (DHO-DH), a mitochondrial enzyme required for de novo pyrimidine synthesis
  • Precise mechanism by which this produces therapeutic effect in MS is unknown, but is thought to involve a reduction in the number of activated lymphocytes in the CNS/periphery

Full Dosing

Adult / usual

  • 7 mg or 14 mg orally once daily, with or without food
  • No titration required; dose selection based on individual efficacy/tolerability considerations
  • Elimination is slow without an accelerated elimination procedure — plasma concentrations may remain detectable for up to 2 years after stopping

Contraindications

  • Patients with severe hepatic impairment
  • Pregnant women, and women of reproductive potential not using reliable contraception
  • Known hypersensitivity to teriflunomide or leflunomide, or to any component of the product (reactions have included anaphylaxis and serious skin reactions)
  • Current treatment with leflunomide

Drug Interactions

  • Warfarin: may decrease INR by approximately 25% despite no change in warfarin pharmacokinetics — monitor INR closely
  • Rosuvastatin: increases exposure; do not exceed rosuvastatin 10 mg once daily when co-administered
  • CYP2C8 substrates (e.g., paclitaxel, pioglitazone, repaglinide): teriflunomide is a moderate CYP2C8 inhibitor — increased substrate exposure possible; monitor
  • CYP1A2 substrates (e.g., duloxetine, theophylline, tizanidine): teriflunomide may weakly induce CYP1A2, decreasing substrate exposure; monitor
  • Organic anion transporter 3 (OAT3) substrates (e.g., methotrexate, furosemide, ciprofloxacin, cefaclor): teriflunomide inhibits OAT3, increasing substrate exposure; monitor
  • BCRP and OATP1B1/1B3 substrates (e.g., rosuvastatin, other statins): increased exposure possible; monitor and consider dose reduction
  • Oral contraceptives: increases ethinylestradiol and levonorgestrel exposure; consider impact on contraceptive selection
  • Live/live-attenuated vaccines: avoid during treatment and for a period after discontinuation (until accelerated elimination confirmed if used)
  • Concomitant hepatotoxic or hematotoxic drugs (e.g., leflunomide, methotrexate): increased risk of additive toxicity; consider more frequent monitoring

Adverse Effects

  • Headache (~16–18%)
  • Diarrhea (~13–14%) and nausea (~8–11%)
  • Alopecia/hair thinning (~10–13%)
  • Elevated ALT (~13–15%)
  • Bone marrow effects — mild decreases in white blood cell count (~15%) and platelet count (~10%)
  • Serious hepatotoxicity, including postmarketing acute liver failure requiring transplant
  • Peripheral neuropathy (sensory and motor), more common in patients >60 years, with diabetes, or on other neurotoxic drugs
  • Interstitial lung disease
  • Serious skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS (drug reaction with eosinophilia and systemic symptoms)
  • Increased blood pressure
  • Serious infections due to immunosuppressive effect; increased risk of tuberculosis reactivation
  • Pancreatitis (reported with higher frequency in pediatric patients)
  • Anaphylaxis and angioedema
  • Cutaneous/mucocutaneous ulcerations and impaired wound healing

Monitoring Parameters

  • Baseline: serum transaminases and bilirubin within 6 months before initiation
  • Monitor ALT levels at least monthly for the first 6 months of therapy
  • Baseline complete blood count (CBC) within 6 months before initiation
  • Screen for latent tuberculosis (tuberculin skin test or blood-based interferon-gamma release assay) before starting
  • Obtain a pregnancy test in females of reproductive potential before initiating treatment
  • Baseline and periodic blood pressure monitoring
  • Discontinue and initiate accelerated elimination if ALT elevation >3x ULN is confirmed on repeat testing, or if drug-induced liver injury is suspected
  • Monitor for signs/symptoms of infection, peripheral neuropathy, interstitial lung disease, and serious skin reactions throughout treatment

Pregnancy & Lactation

  • Contraindicated in pregnancy — animal studies showed teratogenicity and embryolethality at doses lower than the human therapeutic dose
  • Exclude pregnancy before initiation; use reliable contraception during treatment and continue contraception during and after any accelerated elimination procedure until plasma teriflunomide concentration is confirmed <0.02 mg/L
  • If pregnancy occurs during treatment, stop Aubagio immediately and begin an accelerated elimination procedure
  • Men wishing to father a child should discontinue Aubagio and either undergo accelerated elimination or wait until plasma concentration is verified <0.02 mg/L (natural elimination can take up to 2 years); men not planning pregnancy should use effective contraception
  • Accelerated elimination procedure (used for pregnancy, suspected serious adverse event, or desire for rapid clearance): cholestyramine 8 g orally every 8 hours for 11 days (alternative 4 g three times daily if 8 g is not well tolerated), OR oral activated charcoal powder 50 g every 12 hours for 11 days; days need not be consecutive unless rapid elimination is medically necessary
  • Both accelerated elimination regimens produce more than a 98% decrease in plasma teriflunomide concentration by day 11
  • Verify plasma teriflunomide concentration is <0.02 mg/L (two separate tests at least 14 days apart) after accelerated elimination before conception or resuming a drug with a potential fetal interaction
  • Aubagio Pregnancy Registry: encourage enrollment for patients exposed during pregnancy or within 2 years prior to conception (1-800-745-4447, option 2)
  • Lactation: women should not breastfeed during treatment with Aubagio; teriflunomide was detected in the milk of lactating animals and human data are not available

References

  1. FDA Prescribing Information — Aubagio (teriflunomide)

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