AUBAGIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUBAGIO (AUBAGIO).
Teriflunomide inhibits dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme involved in de novo pyrimidine synthesis. This reduces proliferation of activated T and B lymphocytes, thereby attenuating the immune response in multiple sclerosis.
| Metabolism | Teriflunomide is the primary active metabolite of leflunomide. It is metabolized via hydrolysis to minor metabolites and undergoes enterohepatic recycling. CYP450 enzymes play a minor role. Major elimination is via biliary excretion and direct renal excretion. |
| Excretion | Approximately 60% of the dose is excreted in urine (mostly as unchanged drug and minor metabolites) and approximately 40% in feces (mostly as unchanged drug). |
| Half-life | Terminal elimination half-life is 10-13 days. Due to the long half-life, steady-state concentrations are reached after approximately 3 months of once-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 1 L/kg. This moderate volume suggests extensive distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 100% (highly absorbable, minimal first-pass metabolism). |
| Onset of Action | Clinical effect (reduction in relapse rate) observed after 2-3 months of oral therapy, consistent with pharmacokinetic steady-state. |
| Duration of Action | Duration of action is sustained with continuous daily dosing. Pharmacodynamic effects persist for weeks after last dose due to prolonged half-life. |
7 mg or 14 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <25 mL/min). No dose adjustment required for mild to moderate renal impairment. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). Not recommended in moderate hepatic impairment (Child-Pugh B) unless benefit outweighs risk. No dose adjustment for mild impairment (Child-Pugh A). |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; clinical studies included patients up to age 65; use with caution due to potential renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUBAGIO (AUBAGIO).
| Breastfeeding | Excreted in breast milk in animal studies; unknown in humans. M/P ratio not established. Use during breastfeeding contraindicated due to potential for serious adverse effects in nursing infants. |
| Teratogenic Risk | Pregnancy Category X. Teratogenic in animal studies (skeletal malformations, embryolethality). First trimester: risk of major congenital malformations (neural tube defects, craniofacial defects). Second and third trimesters: risk of fetal growth restriction, spontaneous abortion. Avoid use in pregnancy. |
■ FDA Black Box Warning
Hepatotoxicity: Severe liver injury including fatal liver failure has been reported. Obtain transaminase and bilirubin levels within 6 months before initiation. Contraindicated in patients with severe hepatic impairment. Monitor ALT levels at least monthly for 6 months after starting therapy.
| Serious Effects |
Severe hepatic impairment, pregnancy or women of childbearing potential not using effective contraception, hypersensitivity to teriflunomide or leflunomide, current use of leflunomide.
| Precautions | Hepatotoxicity, embryofetal toxicity, increased risk of infection (including tuberculosis reactivation), peripheral neuropathy, increased blood pressure, interstitial lung disease, severe skin reactions (e.g., Stevens-Johnson syndrome), acute renal failure, hyperkalemia, and hematologic effects (thrombocytopenia, neutropenia). |
| Food/Dietary | No specific food restrictions; may be taken with or without food. Avoid alcohol due to hepatotoxicity risk. |
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| Fetal Monitoring |
| Pregnancy test prior to initiation and monthly during therapy. Confirm negative pregnancy test before starting. Monitor liver function (ALT), renal function, and complete blood count periodically. Fetal ultrasound for development assessment if exposed. |
| Fertility Effects | In animal studies, reduced fertility and embryotoxicity observed. Human data limited; potential for impaired fertility in females of reproductive potential. Males: no specific data on spermatogenesis effects. |
| Clinical Pearls | Aubagio (teriflunomide) is a pyrimidine synthesis inhibitor used for relapsing forms of multiple sclerosis (MS). Monitor liver function tests (ALT) monthly for the first 6 months, then every 3-6 months. Check complete blood count and blood pressure at baseline and periodically. Avoid use in patients with severe hepatic impairment. Pregnancy category X; effective contraception is mandatory. Accelerated elimination with cholestyramine or activated charcoal is used for rapid washout. Watch for peripheral neuropathy, pancreatitis, and interstitial lung disease. |
| Patient Advice | Take Aubagio exactly as prescribed, once daily with or without food. · Do not become pregnant while taking this medication; use reliable contraception and notify your doctor immediately if pregnancy occurs. · Report symptoms such as unexplained bleeding, bruising, yellowing of skin or eyes, dark urine, severe fatigue, or abdominal pain. · Avoid alcohol consumption due to risk of liver toxicity. · You may experience hair thinning or diarrhea, which are common and often resolve with continued use. · Inform all healthcare providers that you are taking teriflunomide before any procedures or vaccinations. |