Aubagio Generic Name & Formulations
Aubagio is available as:
- 14 mg: pale blue to pastel blue, pentagonal film-coated tablet with dose strength "14" imprinted on one side and engraved with corporate logo on the other side.
- 7 mg: very light greenish-bluish grey to pale greenish-blue, hexagonal film-coated tablet with dose strength "7" imprinted on one side and engraved with corporate logo on the other side.
Store at 68° F to 77° F (20° C to 25° C) with excursions permitted between 59° F and 86° F (15° C and 30° C).
Aubagio Dosage and Administration
Prior to Treatment Evaluations
Monitoring to Assess Safety
- Obtain transaminase and bilirubin levels within 6 months prior to initiation. Monitor ALT levels at least monthly for 6 months after starting Aubagio.
- Obtain CBCs within 6 months prior to initiation of treatment. Further monitoring should be based on signs/symptoms of infection.
- Prior to initiation, screen patients for latent tuberculosis infection with a tuberculin skin test or blood test for mycobacterium tuberculosis infection.
- Exclude pregnancy prior to initiation of treatment in females of reproductive potential.
- Check blood pressure prior to and periodically thereafter.
Aubagio Boxed Warnings
Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with Aubagio.
Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) >2× the upper limit of normal (ULN) before initiating treatment, should not normally be treated with Aubagio.
Obtain serum transaminase and bilirubin levels within 6 months before initiation of Aubagio therapy. Monitor ALT levels at least monthly for 6 months after initiation. Consider additional monitoring when Aubagio is given with other potentially hepatotoxic drugs.
Consider discontinuing Aubagio if serum transaminase increase (>3×ULN) is confirmed. Monitor serum transaminase and bilirubin on Aubagio therapy, especially in those who develop symptoms suggestive of hepatic dysfunction. If liver injury is suspected to be Aubagio-induced, discontinue Aubagio and start an accelerated elimination procedure; monitor liver tests weekly until normalized. If Aubagio-induced liver injury is unlikely because some other probable cause has been found, resumption of Aubagio therapy may be considered.
Aubagio may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryofetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum recommended human dose (MRHD) of 14 mg/day.
Aubagio is contraindicated for use in pregnant women and in females of reproductive potential not using effective contraception. Exclude pregnancy prior to initiation in females of reproductive potential. Advise females of reproductive potential to use effective contraception during Aubagio treatment and during an accelerated drug elimination procedure after Aubagio treatment. If a woman becomes pregnant while taking Aubagio, discontinue treatment, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve a plasma teriflunomide concentration of <0.02 mg/L. Based on animal data, human plasma concentrations of teriflunomide of <0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryofetal risk.
Procedure for Accelerated Elimination of Teriflunomide
Teriflunomide is eliminated slowly from the plasma. Without an accelerated elimination procedure, it takes on average 8 months to reach plasma concentrations <0.02 mg/L, although because of individual variations in drug clearance it may take as long as 2 years. An accelerated elimination procedure could be used at any time after discontinuation of Aubagio. Elimination can be accelerated by either of the following procedures:
- Administer cholestyramine 8 g every 8 hours for 11 days. If cholestyramine 8 g three times daily is not well tolerated, cholestyramine 4 g three times daily can be used.
- Administer oral activated charcoal powder 50 g every 12 hours for 11 days.
If either elimination procedure is not tolerated well, treatment days do not need to be consecutive unless there is a need to lower teriflunomide plasma concentration rapidly.
At the end of 11 days, both regimens successfully accelerated teriflunomide elimination, leading to >98% decrease in teriflunomide plasma concentrations.
Use of the accelerated elimination procedure may potentially result in return of disease activity if the patient had been responding to Aubagio treatment.
Bone Marrow Effects/Immunosuppression Potential/Infections
Bone Marrow Effects
Compared to baseline in WBC count, a mean decrease of ~15% (mainly neutrophils and lymphocytes) and in platelet count of ~10% were observed in placebo-controlled trials in adult patients with Aubagio 7 mg and 14 mg. The decrease in mean WBC count occurred during the first 6 weeks and WBC count remained low during treatment. Neutrophil count <1.5×109/L and lymphocyte count <0.8×109/L were also observed in the placebo-controlled studies. Cases of thrombocytopenia with Aubagio, including rare cases with platelet counts <50,000/mm3, have been reported in the postmarketing setting.
Obtain CBCs within 6 months before the initiation of Aubagio treatment. Further monitoring should be based on signs/symptoms suggestive of bone marrow suppression.
Risk of Infection/Tuberculosis Screening
In patients with active acute or chronic infections, do not start Aubagio treatment until the infection(s) is resolved. If a serious infection occurs, consider interrupting treatment and using an accelerated elimination procedure. Reassess the benefits and risks prior to resumption of therapy.
Aubagio is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections. Aubagio has immunosuppression potential and may cause patients to be more susceptible to infections, including opportunistic infections.
Cases of tuberculosis have been seen in clinical studies with Aubagio in adult patients. Prior to initiation, screen patients for latent tuberculosis infection with a tuberculin skin test or with a blood test for mycobacterium tuberculosis infection. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to Aubagio therapy.
No clinical data are available on the efficacy and safety of live vaccinations in patients taking Aubagio. Vaccination with live vaccines is not recommended. Consider the long half-life of Aubagio when contemplating use of a live vaccine after stopping Aubagio.
The risk of malignancy (esp. lymphoproliferative disorders), is increased with the use of certain immunosuppressive medications. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the Aubagio clinical trials, but larger and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with Aubagio.
Aubagio can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.
Serious Skin Reactions
Cases of serious skin reactions (sometimes fatal), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with Aubagio. Fatal outcomes were reported in one case of TEN.
Drug Reaction and Eosinophilia and Systemic Symptoms
Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with Aubagio. One fatal case of DRESS that occurred in close temporal association (34 days) has been reported in the postmarketing setting.
DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved.
Discontinue Aubagio, unless an alternative etiology for the signs/symptoms is established, and begin an accelerated elimination procedure immediately. In such cases, patients should not be re-exposed to teriflunomide.
Patients >60 years of age, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. If peripheral neuropathy symptoms develops, consider discontinuing Aubagio and performing an accelerated elimination procedure.
Increased Blood Pressure
Check blood pressure before the start of Aubagio treatment and periodically thereafter. Manage appropriately if elevated blood pressure develops.
Interstitial lung disease, including acute interstitial pneumonitis, has been reported with Aubagio in the postmarketing setting.
Interstitial lung disease may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. If new onset or worsening pulmonary symptoms develop, evaluate promptly. Consider initiation of an accelerated elimination procedure if discontinuation of Aubagio is necessary.
Concomitant Use with Immunosuppressive or Immunomodulating Therapies
Coadministration with antineoplastic or immunosuppressive therapies used for treatment of multiple sclerosis has not been evaluated. Safety studies in which Aubagio was concomitantly administered with other immune modulating therapies for up to 1 year (interferon beta, glatiramer acetate) did not reveal any specific safety concerns. The long term safety of these combinations in the treatment of multiple sclerosis has not been established.
Aubagio is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of the potential for fetal harm based on animal data.
In animal reproduction studies, oral administration of teriflunomide during organogenesis caused teratogenicity and embryolethality at plasma exposures (AUC) lower than that at the maximum recommended human dose (MRHD) of 14 mg/day. Available human data from pregnancy registries, clinical trials, pharmacovigilance cases, and published literature are too limited to draw any conclusions, but they do not clearly indicate increased birth defects or miscarriage associated with inadvertent teriflunomide exposure in the early first trimester when followed by an accelerated elimination procedure.
Exclude pregnancy prior to initiation of treatment in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment.
Nursing Mother Considerations
There are no data on the presence of Aubagio in human milk, the effects on the breastfed infant, or the effects on milk production. Teriflunomide was detected in rat milk following a single oral dose.
Because of the potential for adverse reactions in a breastfed infant from Aubagio, women should not breastfeed during treatment with Aubagio.
Safety and effectiveness in pediatric patients have not been established.
Effectiveness of Aubagio for the treatment of relapsing form of multiple sclerosis in pediatric patients (10 to 17 years of age) was not established in an adequate and well-controlled clinical study in 166 patients for up to 96 weeks.
Clinical studies of Aubagio did not include patients >65 years old.
Median time to reach maximum plasma concentrations is between 1 to 4 hours post dose following oral administration of teriflunomide.
Food does not have a clinically relevant effect on teriflunomide pharmacokinetics.
Teriflunomide is extensively bound to plasma protein (>99%) and is mainly distributed in plasma.
Mainly through direct biliary excretion of unchanged drug as well as renal excretion of metabolites. Over 21 days, 60.1% of the administered dose is excreted via feces (37.5%) and urine (22.6%). After an accelerated elimination procedure with cholestyramine, an additional 23.1% was recovered (mostly in feces).
Aubagio Adverse Reactions
Headache, ALT increased, diarrhea, alopecia, nausea, paresthesia; hepatotoxicity, bone marrow suppression, immunosuppression potential, infection (consider suspending therapy), hypersensitivity, serious skin reactions (eg, SJS, TEN, DRESS; discontinue if occur), peripheral neuropathy, hypertension, interstitial lung disease.
Aubagio Clinical Trials
Four randomized, controlled, double-blind clinical trials established the efficacy of Aubagio in patients with relapsing forms of multiple sclerosis.
Study 1 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 26 months in patients with relapsing forms of multiple sclerosis. Patients were required to have a diagnosis of multiple sclerosis exhibiting a relapsing clinical course, with or without progression, and to have experienced at least 1 relapse over the year preceding the trial or at least 2 relapses over the 2 years preceding the trial. The primary endpoint was the annualized relapse rate (ARR).
Patients (n=1088) were randomized to receive Aubagio 7 mg (n=366), Aubagio 14 mg (n=359), or placebo (n=363). At trial entry, patients had an Expanded Disability Status Scale (EDSS) score ≤5.5; mean age of 38 years, mean disease duration of 5 years, and mean EDSS at baseline of 2.7.
Findings showed a statistically significant reduction in ARR for patients who received Aubagio 7 mg (0.370, P=0.0002) or 14 mg (0.369, P=0.0005), compared to those who received placebo (0.539). There was a consistent reduction of the ARR noted in subgroups defined by sex, age group, prior multiple sclerosis therapy, and baseline disease activity.
There was a statistically significant reduction in the relative risk of disability progression at week 108 sustained for 12 weeks (as measured by at least a 1-point increase from baseline EDSS ≤5.5 or a 0.5 point increase for those with a baseline EDSS >5.5) in the Aubagio 14 mg (20.2%, P <0.05) group compared to placebo (27.3%).
The effect of Aubagio on several magnetic resonance imaging (MRI) variables, including the total lesion volume of T2 and hypointense T1 lesions, was assessed in Study 1. The change in total lesion volume from baseline was significantly lower in the Aubagio 7 mg (0.755, P=0.0317) and 14 mg (0.345, P=0.0003) groups than in the placebo group (1.127). Patients in both Aubagio groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than those in the placebo group (0.570, P <0.0001 and 0.261, P <0.0001 vs 1.331, respectively).
Study 2 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 40 months in patients with relapsing forms of multiple sclerosis. Patients were required to have a diagnosis of multiple sclerosis exhibiting a relapsing clinical course and to have experienced at least 1 relapse over the year preceding the trial, or at least 2 relapses over the 2 years preceding the trial. The primary end point was the ARR.
Patients (n=1165) received Aubagio 7 mg (n=407), Aubagio 14 mg (n=370), or placebo (n=388). At trial entry, patients had a mean age of 38 years, a mean disease duration of 5 years, and a mean EDSS at baseline of 2.7.
At study end point, there was a statistically significant reduction in the ARR for patients who received Aubagio 7 mg (0.389, P=0.0183) or 14 mg (0.319, P=0.0001) compared to those who received placebo (0.501). There was a consistent reduction of the ARR noted in subgroups defined by sex, age group, prior multiple sclerosis therapy, and baseline disease activity.
There was a statistically significant reduction in the relative risk of disability progression at week 108 sustained for 12 weeks (as measured by at least a 1-point increase from baseline EDSS ≤5.5 or a 0.5 point increase for those with a baseline EDSS >5.5) in the Aubagio 14 mg (15.8%, P <0.05) group compared to placebo (19.7%).
Study 3 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 108 weeks in patients with relapsing multiple sclerosis. Patients were required to have had a first clinical event consistent with acute demyelination occurring within 90 days of randomization with 2 or more T2 lesions at least 3 mm in diameter that were characteristic of multiple sclerosis.
Patients (n=614) received Aubagio 7 mg (n=203), Aubagio 14 mg (n=214), or placebo (n=197). At trial entry, patients had a mean age of 32 years, EDSS at baseline of 1.7, and mean disease duration of two months. Results showed that the proportion of patients free of relapse was greater in the Aubagio 7 mg (70.5%, P <0.05) and 14 mg (72.2%, P <0.05) groups than in the placebo group (61.7%).
Study 4 was a randomized, double-blind, placebo-controlled clinical trial that assessed the effect of Aubagio in multiple sclerosis patients with relapse based on MRI activity.
The MRI scan was to be performed at baseline, 6 weeks, 12 weeks, 18 weeks, 24 weeks, 30 weeks, and 36 weeks after treatment initiation. A total of 179 patients were randomized to Aubagio 7 mg (n=61), Aubagio 14 mg (n=57), or placebo (n=61). Baseline demographics were consistent across treatment groups. The primary endpoint was the average number of unique active lesions/MRI scan during treatment.
The mean number of unique active lesions per brain MRI scan during the 36-week treatment period was lower in patients treated with Aubagio 7 mg (1.06) and 14 mg (0.98) as compared to placebo (2.69), the difference being statistically significant for both (P=0.0234 and P=0.0052, respectively).
Aubagio Patient Counseling
Inform patients that Aubagio may cause liver injury, which can be life-threatening, and that their liver enzymes will be checked before starting Aubagio and at least monthly for 6 months after initiation.
Advise patients that they should contact their physician if they have any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.
Advise females of reproductive potential:
- of the potential for fetal harm if Aubagio is taken during pregnancy
- to notify their healthcare provider immediately if a pregnancy occurs or is suspected
- to use effective contraception during treatment with Aubagio and until the teriflunomide plasma concentration is verified to be <0.02 mg/L.
- Instruct men taking Aubagio and not planning to father a child to use effective contraception to minimize any possible risk to the fetus; their female partners should also use effective contraception.
- Advise men planning to father a child to discontinue use of Aubagio and undergo an accelerated elimination procedure.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Aubagio during pregnancy.
Availability of an Accelerated Elimination Procedure
Advise patients that Aubagio may stay in the blood for up to 2 years after the last dose and that an accelerated elimination procedure may be used if needed.
Risk of Infections
Inform patients that they may develop a lowering of their white blood cell counts and that their blood counts will be checked before starting Aubagio.
Inform patients that they may be more likely to get infections when taking Aubagio and that they should contact their physician if they develop symptoms of infection, particularly in case of fever.
Advise patients that the use of some vaccines should be avoided during treatment with Aubagio and for at least 6 months after discontinuation.
Advise patients to discontinue Aubagio and seek immediate medical attention if any signs/symptoms of a hypersensitivity reaction occur. Signs and symptoms can include dyspnea, urticaria, angioedema involving the lips, eyes, throat, or tongue, or skin rash.
Serious Skin Reactions
Advise patients to discontinue Aubagio and seek immediate medical attention if any signs of a serious skin reaction, such as SJS or TEN, occur. Signs and symptoms can include rash, mouth sores, blisters, or peeling skin.
Instruct patients and caregivers that a fever or rash associated with signs of other organ system involvement (eg, lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately. Aubagio should be discontinued immediately if a serious hypersensitivity reaction is suspected.
Inform patients that they may develop peripheral neuropathy. Advise patients that they should contact their physician if they develop symptoms of peripheral neuropathy, such as numbness or tingling of hands or feet.
Increased Blood Pressure
Inform patients that Aubagio may increase blood pressure.
Advise females not to breastfeed during treatment with Aubagio.
Cost Savings Program
Aubagio Support Program is available here.