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Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide tablets in the postmarketing setting [see Warnings and Precautions (5.1) ] . Concomitant use of teriflunomide tablets with other hepatotoxic drugs may increase the risk of severe liver injury.  Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets  [see Warnings and Precautions (5.1) ] . If drug induced liver injury is suspected, discontinue teriflunomide tablets and start an accelerated elimination procedure with cholestyramine or charcoal  [see Warnings and Precautions (5.3 )] . Teriflunomide tablet is contraindicated in patients with severe hepatic impairment  [see Contraindications ( 4) ].   Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide tablets. Embryofetal Toxicity Teriflunomide tablet is contraindicated for use in pregnant women and in females 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 tablets in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide tablet treatment and during an accelerated drug elimination procedure after teriflunomide tablet treatment. Stop teriflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant   [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), and Clinical Pharmacology ( 12.3 )]

Teriflunomide tablet is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

The recommended dose of teriflunomide tablets is 7mg or 14 mg orally once daily. Teriflunomide tablets can be taken with or without food. Monitoring to Assess Safety. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablet therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets [see  Warnings and Precautions (5.1) ] . Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide tablets. Further monitoring should be based on signs and symptoms of infection [see Warnings and Precautions (5.4) ] . Prior to initiating teriflunomide tablets, screen patients for latent tuberculosis infection with a tuberculin skin test or blood test for mycobacterium tuberculosis infection [ see Warnings and Precautions (5.4) ] . Exclude pregnancy prior to initiation of treatment with teriflunomide tablets in females of reproductive potential [see  Warnings and Precautions  (5.2) ]. Check blood pressure before start of teriflunomide tablet treatment and periodically thereafter [see  Warnings and Precautions  (5.9 )].

Teriflunomide tablets are available as 7 mg and 14 mg tablets. The 14 mg tablet is a blue (pale blue to pastel blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “14” on one side. Each tablet contains 14 mg of teriflunomide. The 7 mg tablet is a green (light greenish-blue grey to pale greenish-blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “7” on one side. Each tablet contains 7 mg of teriflunomide. Teriflunomide 14 mg tablets are supplied as: NDC 70512-0851-28  Carton of 28 tablets containing 1 wallet composed of 2 folded blister cards of 14 tablets per blister card Teriflunomide 7 mg tablets are supplied as: NDC 70512-0850-28   Carton of 28 tablets containing 1 wallet composed of 2 folded blister cards of 14 tablets per blister card Store at 68°F to 77°F (20°C to 25°C) [see USP Controlled Room Temperature] with excursions permitted between 59°F and 86°F (15°C and 30°C).

Teriflunomide tablet is contraindicated in/with: Patients with severe hepatic impairment [see  Warnings and Precautions  (5.1) ] . Pregnant women and females of reproductive potential not using effective contraception. Teriflunomide tablets may cause fetal harm [see  Warnings and Precautions   (5.2 , 5.3) and  Use in Specific Populations  (8.1) ]. Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablets. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions  (5.5) ]. Co-administration with leflunomide [see  Clinical Pharmacology (12.3) ].

Teriflunomide is an oral de novo pyrimidine synthesis inhibitor of the DHO-DH enzyme, with the chemical name (Z)-2-Cyano-3-hydroxy-but-2-enoic acid-(4­ trifluoromethylphenyl)-amide. Its molecular weight is 270.21, and the empirical formula is C 12 H 9 F 3 N 2 O 2 with the following chemical structure: Teriflunomide is a white to almost white powder that is sparingly soluble in acetone, slightly soluble in polyethylene glycol and ethanol, very slightly soluble in isopropanol and practically insoluble in water. Teriflunomide is formulated as film-coated tablets for oral administration. Teriflunomide tablets contain 7 mg and 14 mg of teriflunomide and the following inactive ingredients: lactose monohydrate, hydroxypropylcellulose, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The film coating for the 7mg and 14mg tablets is made of hypromellose, hydroxypropylcellulose, cottonseed oil, talcum, titanium dioxide, and FD & C Blue no. 2 Al-Lake. In addition to these, the 7mg tablet film coating includes FD & C Yellow no. 5 (tartrazine). The 14mg tablet includes FD & C Red no. 40.

Effect of Teriflunomide Tablets on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . In patients taking teriflunomide tablets, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology ( 12.3 )] .

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). A Medication Guide is required for distribution with teriflunomide tablets. Hepatotoxicity Inform patients that teriflunomide tablets may cause liver injury, which can be life-threatening, and that their liver enzymes will be checked before starting teriflunomide tablets and at least monthly for 6 months after starting teriflunomide tablets [see Dosage and Administration ( 2 ) and Warnings and Precautions ( 5.1 )] . 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. Embryofetal Toxicity Advise females of reproductive potential of the potential for fetal harm if teriflunomide tablets is taken during pregnancy to notify their healthcare provider immediately if a pregnancy occurs or is suspected to use effective contraception during treatment with teriflunomide tablets and until the teriflunomide plasma concentration is verified to be less than 0.02 mg/L [see Warnings and Precautions ( 5.2 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), Clinical Pharmacology ( 12.3 )]. Instruct men taking teriflunomide tablets and not wishing 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 wishing to father a child to discontinue use of teriflunomide tablets and undergo an accelerated elimination procedure. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Teriflunomide during pregnancy [see Use in Specific Populations ( 8.1 , 8.3 ), Clinical Pharmacology ( 12.3 )] . Availability of an Accelerated Elimination Procedure Advise patients that teriflunomide 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 [see Warnings and Precautions ( 5.3 )] . 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 teriflunomide tablets. Inform patients that they may be more likely to get infections when taking teriflunomide tablets and that they should contact their physician if they develop symptoms of infection, particularly in case of fever [see Warnings and Precautions ( 5.4 )] . Advise patients that the use of some vaccines should be avoided during treatment with teriflunomide tablets and for at least 6 months after discontinuation. Hypersensitivity Reactions Advise patients to discontinue teriflunomide tablets and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur [see Contraindications ( 4 ) and Warnings and Precautions ( 5.5 )] . 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 teriflunomide tablets and seek immediate medical attention if any signs of a serious skin reaction, such as SJS or TEN,occur [see Warnings and Precautions ( 5.6 )] . Signs and symptoms can include rash, mouth sores, blisters, or peeling skin. DRESS/Multi-organ Hypersensitivity Instruct patients and caregivers that a fever or rash associated with signs of other organ system involvement (e.g., lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately. Teriflunomide tablets should be discontinued immediately if a serious hypersensitivity reaction is suspected [see Warnings and Precautions ( 5.7 )] . Peripheral Neuropathy 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 [see Warnings and Precautions ( 5.8 )] . Increased Blood Pressure Inform patients that teriflunomide tablets may increase blood pressure [see Warnings and Precautions ( 5.9 )] . Lactation Advise females not to breastfeed during treatment with teriflunomide tablets [see Use in Specific Populations ( 8.2 )] . Manfuactured for: Sola Pharmaceuticals LLC Baton Rouge, LA 70810 Manufactured in Malta Iss.  09/2023 Medication Guide Teriflunomide (ter” i floo’ noe mide) Tablets, for oral use

Safety and effectiveness in pediatric patients have not been established.   Pancreatitis has been reported in adults in the postmarketing setting, but appears to occur at higher frequency in the pediatric population [see Warnings and Precautions ( 5.11 ) ] .  Additionally, elevated or abnormal blood creatine phosphokinase was reported. Juvenile Animal Toxicity Data Oral administration of teriflunomide (0, 0.3, 3, or 6 mg/kg/day) to young rats on postnatal days 21 to 70 resulted in suppression of immune function (T-cell dependent antibody response) at the mid and high doses, and adverse effects on male reproductive organs (reduced sperm count) and altered neurobehavioral function (increased locomotor activity) at the high dose. Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Sanofi-Aventis U.S. LLC’s Aubagio ® (teriflunomide) tablets.  However, due to Sanofi-Aventis U.S. LLC’s marketing exclusivity rights, this drug product is not labeled with that information.

Clinical studies of teriflunomide tablets did not include patients over 65 years old.

Carcinogenesis No evidence of carcinogenicity was observed in lifetime carcinogenicity bioassays in mouse and rat. In mouse, teriflunomide was administered orally at doses up to 12 mg/kg/day for up to 95 to 104 weeks; plasma teriflunomide exposures (AUC) at the highest dose tested are approximately 3 times that in humans at the maximum recommended human dose (MRHD, 14 mg/day). In rat, teriflunomide was administered orally at doses up to 4 mg/kg/day for up to 97 to 104 weeks; plasma teriflunomide AUCs at the highest doses tested are less than that in humans at the MRHD. Mutagenesis Teriflunomide was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro HPRT assay, and in in vivo micronucleus and chromosomal aberration assays. Teriflunomide was positive in an in vitro chromosomal aberration assay in human lymphocytes, with and without metabolic activation. Addition of uridine (to supplement the pyrimidine pool) reduced the magnitude of the clastogenic effect; however, teriflunomide was positive in the in vitro chromosomal aberration assay, even in the presence of uridine. 4-Trifluoromethylaniline (4-TFMA), a minor metabolite of teriflunomide, was positive in the in vitro bacterial reverse mutation (Ames) assay, the in vitro HPRT assay, and the in vitro chromosomal aberration assay in mammalian cells. 4-TFMA was negative in in vivo micronucleus and chromosomal aberration assays. Impairment of Fertility Oral administration of teriflunomide (0, 1, 3, 10 mg/kg/day) to male rats prior to and during mating (to untreated females) resulted in no adverse effects on fertility; however, reduced epididymal sperm count was observed at the mid and high doses tested. The no-effect dose for reproductive toxicity in male rats (1 mg/kg) is less than the MRHD on a mg/m 2 basis. Oral administration of teriflunomide (0, 0.84, 2.6, 8.6 mg/kg/day) to female rats, prior to and during mating (to untreated males) and continuing to gestation day 6, resulted in embryolethality, reduced fetal body weight, and/or malformations at all doses tested. Due to marked embryolethality at the highest dose tested, no fetuses were available for evaluation. The lowest dose tested is less than the MRHD on a mg/m 2 basis.

The following serious adverse reactions are described elsewhere in the prescribing information: Hepatotoxicity [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Bone Marrow Effects/Immunosuppression Potential/Infections [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions  [see Contraindications ( 4 ) and Warnings and Precautions ( 5.5 )] Serious Skin Reactions [see Warnings and Precautions ( 5.6 )] Drug Reaction with Eosinophilia and Systemic Symptoms  [see Warnings and Precautions ( 5.7 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.8 )] Increased Blood Pressure [see Warnings and Precautions ( 5.9 )] Respiratory Effects [see Warnings and Precautions ( 5.10) ] Pancreatitis in Pediatric Patients [ see Warnings and Precautions ( 5.11 ) ]

There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects. In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions ( 5.3 )] .

Four randomized, controlled, double-blind clinical trials established the efficacy of teriflunomide tablets in patients with relapsing forms of multiple sclerosis. Study 1 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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 one relapse over the year preceding the trial or at least two relapses over the two years preceding the trial. Patients were required not to have received interferon-beta for at least four months, or any other multiple sclerosis medication for at least six months before entering the study, nor were these medications permitted during the study. Neurological evaluations were to be performed at screening, every 12 weeks until week 108, and after suspected relapses. MRI was to be performed at screening, and at Week 24, 48, 72, and 108. The primary endpoint was the annualized relapse rate (ARR). In Study 1, 1088 patients were randomized to receive teriflunomide tablets 7 mg (n=366), teriflunomide tablets 14 mg (n=359), or placebo (n=363). At entry, patients had an Expanded Disability Status Scale (EDSS) score ≤5.5. Patients had a mean age of 38 years, mean disease duration of 5 years, and mean EDSS at baseline of 2.7. A total of 91% of patients had relapsing remitting multiple sclerosis, and 9% had a progressive form of multiple sclerosis with relapses. The mean duration of treatment was 635, 627, and 631 days for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. The percentage of patients who completed the study treatment period was 75%, 73%, and 71% for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. There was a statistically significant reduction in ARR for patients who received teriflunomide tablets 7 mg or teriflunomide tablets 14 mg, compared to patients who received placebo (see Table 2 ). 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 teriflunomide tablets 14 mg group compared to placebo (see Table 2 and Figure 1 ). The effect of teriflunomide tablets 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 teriflunomide tablets 7 mg and teriflunomide tablets 14 mg groups than in the placebo group. Patients in both teriflunomide tablets groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than those in the placebo group (see Table 2 ). Table 2:  Clinical and MRI Results of Study 1   Teriflunomide Tablets 7 mg N=365 Teriflunomide Tablets 14 mg N=358 Placebo N=363 1 Total lesion volume: sum of T2 and hypointense T1 lesion volume in mL 2 p-values based on cubic root transformed data for total lesion volume Clinical Endpoints Annualized relapse rate 0.370 (p=0.0002) 0.369 (p=0.0005) 0.539 Relative risk reduction 31% 31% – Percent of patients remaining relapse-free at week 108 53.7% 56.5% 45.6% Percent disability progression at week 108 21.7% (p=0.084) 20.2% (p=0.028) 27.3% Hazard ratio 0.76 0.70 – MRI Endpoints Median change from baseline in Total lesion volume 1 (mL) at week 108 0.755 (p=0.0317) 2 0.345 (p=0.0003) 2 1.127 Mean number of Gd-enhancing T1-lesions per scan 0.570 (p < 0.0001) 0.261 (p < 0.0001) 1.331 Study 2 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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 one relapse over the year preceding the trial, or at least two relapses over the two years preceding the trial. Patients were required not to have received any multiple sclerosis medication for at least three months before entering the trial, nor were these medications permitted during the trial. Neurological evaluations were to be performed at screening, every 12 weeks until completion, and after every suspected relapse. The primary end point was the ARR. A total of 1165 patients received teriflunomide tablets 7 mg (n=407), teriflunomide tablets 14 mg (n=370), or placebo (n=388). Patients had a mean age of 38 years, a mean disease duration of 5 years, and a mean EDSS at baseline of 2.7. A total of 98% of patients had relapsing remitting multiple sclerosis, and 2% had a progressive form of multiple sclerosis with relapses. The mean duration of treatment was 552, 567, and 571 days for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. The percentage of patients who completed the study treatment period was 67%, 66%, and 68% for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. There was a statistically significant reduction in the ARR for patients who received teriflunomide tablets 7 mg or teriflunomide tablets 14 mg compared to patients who received placebo (see Table 3 ). 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 teriflunomide tablets 14 mg group compared to placebo (see Table 3 and Figure 2 ). Table 3: Clinical Results of Study 2   Teriflunomide Tablets 7 mg N=407 Teriflunomide Tablets 14 mg N=370 Placebo N=388 Clinical Endpoints Annualized relapse rate 0.389 (p=0.0183) 0.319 (p=0.0001) 0.501 Relative risk reduction 22% 36% – Percent of patients remaining relapse-free at week 108 58.2% 57.1% 46.8% Percent disability progression at week 108 21.1% (p=0.762) 15.8% (p=0.044) 19.7% Hazard ratio 0.96 0.69 – Study 3 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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. A total of 614 patients received teriflunomide tablets 7 mg (n=203), teriflunomide tablets 14 mg (n=214), or placebo (n=197). Patients had a mean age of 32 years, EDSS at baseline of 1.7, and mean disease duration of two months. The proportion of patients free of relapse was greater in the teriflunomide tablets 7 mg (70.5%, p < 0.05) and teriflunomide tablets 14 mg (72.2%, p < 0.05) groups than in the placebo group (61.7%). The effect of teriflunomide tablets on MRI activity was also demonstrated in Study 4, a randomized, double-blind, placebo-controlled clinical trial of multiple sclerosis patients with relapse. In Study 4, MRI 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 teriflunomide tablets 7 mg (n=61), teriflunomide tablets 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 teriflunomide tablets 7 mg (1.06) and teriflunomide tablets 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).

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Teriflunomide during pregnancy. Healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2. Risk Summary Teriflunomide tablet 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 [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . In animal reproduction studies in rat and rabbit, 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 [see Data ] . 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 [see Clinical Considerations and Data ] . There are no human data pertaining to exposures later in the first trimester or beyond. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. Clinical Considerations Fetal/Neonatal adverse reactions Lowering the plasma concentration of teriflunomide by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease the risk to the fetus from teriflunomide tablets. The accelerated drug elimination procedure includes verification that the plasma teriflunomide concentration is less than 0.02 mg/L [see Warnings and Precautions ( 5.3 ) and Clinical Pharmacology ( 12.3 )]. Data Human data Available human data are limited. Prospectively reported data (from clinical trials and postmarketing reports) from > 150 pregnancies in patients treated with teriflunomide tablets and > 300 pregnancies in patients treated with leflunomide have not demonstrated an increased rate of congenital malformations or miscarriage following teriflunomide exposure in the early first trimester when followed by an accelerated elimination procedure. Specific patterns of major congenital malformations in humans have not been observed. Limitations of these data include an inadequate number of reported pregnancies from which to draw conclusions, the short duration of drug exposure in reported pregnancies, which precludes a full evaluation of the fetal risks, incomplete reporting, and the inability to control for confounders (such as underlying maternal disease and use of concomitant medications). Animal data When teriflunomide (oral doses of 1, 3, or 10 mg/kg/day) was administered to pregnant rats throughout the period of organogenesis, high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death were observed at doses not associated with maternal toxicity. Adverse effects on fetal development were observed following dosing at various stages throughout organogenesis. Maternal plasma exposure at the no-effect level (1.0 mg/kg/day) for fetal developmental toxicity in rats was less than that in humans at the maximum recommended human dose (MRHD, 14 mg/day). Administration of teriflunomide (oral doses of 1, 3.5, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death at doses associated with minimal maternal toxicity. Maternal plasma exposure at the no-effect dose (1.0 mg/kg/day) for fetal developmental toxicity in rabbits was less than that in humans at the MRHD. In studies in which teriflunomide (oral doses of 0.05, 0.1, 0.3, 0.6, or 1.0 mg/kg/day) was administered to rats during gestation and lactation, decreased growth, eye and skin abnormalities, and high incidences of malformation (limb defects) and postnatal death were observed in the offspring at doses not associated with maternal toxicity. Maternal plasma exposure at the no-effect dose for prenatal and postnatal developmental toxicity in rats (0.10 mg/kg/day) was less than that in humans at the MRHD. In animal reproduction studies of leflunomide, embryolethality and teratogenic effects were observed in pregnant rat and rabbit at or below clinically relevant plasma teriflunomide exposures (AUC). In published reproduction studies in pregnant mice, leflunomide was embryolethal and increased the incidence of malformations (craniofacial, axial skeletal, heart and great vessel). Supplementation with exogenous uridine reduced the teratogenic effects in pregnant mice, suggesting that the mode of action (inhibition of mitochondrial enzyme dihydroorotate dehydrogenase) is the same for therapeutic efficacy and developmental toxicity. At recommended doses in humans, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide.

Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide tablets in the postmarketing setting. Patients with pre-existing liver disease and patients taking other hepatotoxic drugs may be at increased risk for developing liver injury when taking teriflunomide tablets. Clinically significant liver injury can occur at any time during treatment with teriflunomide tablets. Patients with pre-existing acute or chronic liver disease, or those with serum alanine  aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with teriflunomide tablets. Teriflunomide tablets is contraindicated in patients with severe hepatic impairment [see  Contraindications   (4) ] . In placebo-controlled trials in adult patients, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving teriflunomide tablets 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment. Half of the cases returned to normal without drug discontinuation. In clinical trials, if ALT elevation was greater than three times the ULN on two consecutive tests, teriflunomide tablet was discontinued and patients underwent an accelerated elimination procedure [see Warnings and Precautions (5.3)] . Of the patients who underwent discontinuation and accelerated elimination in controlled trials, half returned to normal or near normal values within 2 months. One patient in the controlled trials in adult patients developed ALT 32 times the ULN and jaundice 5 months after initiation of teriflunomide tablets 14 mg treatment. The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure. Teriflunomide-induced liver injury in this patient could not be ruled out. Obtain serum transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablet therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets. Consider additional monitoring when teriflunomide tablet is given with other potentially hepatotoxic drugs. Consider discontinuing teriflunomide tablets if serum transaminase increase (greater than three times the ULN) is confirmed. Monitor serum transaminase and bilirubin on teriflunomide tablet therapy, particularly in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. If liver injury is suspected to be teriflunomide-induced, discontinue teriflunomide tablets and start an accelerated elimination procedure [see  Warnings and Precautions   (5.3) ] and monitor liver tests weekly until normalized. If teriflunomide-induced liver injury is unlikely because some other probable cause has been found, resumption of teriflunomide tablet therapy may be considered.

Read this Medication Guide before you start using teriflunomide tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about teriflunomide tablets? Teriflunomide tablets may cause serious side effects, including: Liver problems: Teriflunomide tablets may cause serious liver problems, including liver failure that can be life-threatening and may require a liver transplant. Your risk of developing serious liver problems may be higher if you already have liver problems or take other medicines that also affect your liver. Your doctor should do blood tests to check your liver: within 6 months before you start taking teriflunomide tablets 1 time a month for 6 months after you start taking teriflunomide tablets Call your doctor right away if you have any of the following symptoms of liver problems: nausea vomiting stomach pain loss of appetite tiredness your skin or the whites of your eyes turn yellow dark urine Harm to your unborn baby: Teriflunomide tablets may cause harm to your unborn baby. Do not take teriflunomide tablets if you are pregnant. Do not take teriflunomide tablets unless you are using effective birth control. If you are a female, you should have a pregnancy test before you start taking teriflunomide tablets. Use effective birth control during your treatment with teriflunomide tablets. After stopping teriflunomide tablets, continue using effective birth control until you have blood tests to make sure your blood levels of teriflunomide are low enough. If you become pregnant while taking teriflunomide tablets or within 2 years after you stop taking it, tell your doctor right away. Teriflunomide Tablets Pregnancy Registry. If you become pregnant while taking Teriflunomide or during the 2 years after you stop taking Teriflunomide, talk to your doctor about enrolling in the Teriflunomide Pregnancy Registry at 1-800-745-4447, option 2. The purpose of this registry is to collect information about your health and your baby’s health. For men taking teriflunomide tablets: If your female partner plans to become pregnant, you should stop taking teriflunomide tablets and ask your doctor how to quickly lower the levels of teriflunomide in your blood. If your female partner does not plan to become pregnant, you and your female partner should use effective birth control during your treatment with teriflunomide tablets. Teriflunomide remains in your blood after you stop taking it, so continue using effective birth control until teriflunomide blood levels have been checked and they are low enough. Teriflunomide may stay in your blood for up to 2 years after you stop taking it. Your doctor can prescribe a medicine to help lower your blood levels of teriflunomide more quickly. Talk to your doctor if you want more information about this. What is Teriflunomide Tablet? Teriflunomide tablet is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is not known if teriflunomide tablet is safe and effective in children. Who should not take teriflunomide tablets? Do not take teriflunomide tablets if you: have severe liver problems are pregnant or are of childbearing age and not using effective birth control have had an allergic reaction to leflunomide, teriflunomide, or any other ingredients in teriflunomide tablets. Please see the end of this Medication Guide for a complete list of ingredients in teriflunomide. take a medicine called leflunomide What should I tell my doctor before taking teriflunomide tablets? Before you take teriflunomide tablets, tell your doctor about all of your medical conditions, including if you: have liver or kidney problems have a fever or infection, or you are unable to fight infections have numbness or tingling in your hands or feet that is different from your MS symptoms have diabetes have had serious skin problems when taking other medicines have breathing problems have high blood pressure are breastfeeding or plan to breastfeed. It is not known if teriflunomide passes into your breast milk. You and your doctor should decide if you will take teriflunomide tablets or breastfeed. You should not do both. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using teriflunomide tablets and other medicines may affect each other causing serious side effects. Teriflunomide tablets may affect the way other medicines work, and other medicines may affect how teriflunomide tablets work. Especially tell your doctor if you take medicines that could raise your chance of getting infections, including medicines used to treat cancer or to control your immune system. Ask your doctor or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine. How should I take teriflunomide tablets? Take teriflunomide tablets exactly as your doctor tells you to take it. Take teriflunomide tablets 1 time each day. Take teriflunomide tablets with or without food. What are possible side effects of teriflunomide tablets? Teriflunomide tablets may cause serious side effects, including: see “ What is the most important information I should know about teriflunomide tablets? ” decreases in your white blood cell count. Your white blood cell counts should be checked before you start taking teriflunomide tablets. When you have a low white blood cell count you: may have more frequent infections. You should have a skin test for TB (tuberculosis) before you start taking teriflunomide tablets. Tell your doctor if you have any of these symptoms of an infection: fever tiredness body aches chills nausea vomiting should not receive certain vaccinations during your treatment with teriflunomide tablets and for 6 months after your treatment with teriflunomide tablets ends. allergic reactions. Stop taking teriflunomide tablets and call your doctor right away or get emergency medical help if you have difficulty breathing , itching, swelling on any part of your body including in your lips, eyes, throat, or tongue. serious skin reactions. Teriflunomide tablets may cause serious skin reactions that may lead to death. Stop taking teriflunomide tablets and call your doctor right away or get emergency medical help if you have any of the following symptoms: rash or redness and peeling, mouth sores or blisters. other types of allergic reactions or serious problems that may affect different parts of the body such as your liver, kidneys, heart, or blood cells. You may or may not have a rash with these types of reactions. Other symptoms you may have are: severe muscle pain swollen lymph glands swelling of your face unusual bruising or bleeding weakness or tiredness yellowing of your skin or the white part of your eyes If you have a fever or rash with any of the above symptoms, stop taking teriflunomide and call your doctor right away. numbness or tingling in your hands or feet that is different from your MS symptoms. You have a higher chance of getting these symptoms if you: are over 60 years of age take certain medicines that affect your nervous system have diabetes Tell your doctor if you have numbness or tingling in your hands or feet that is different from your MS. high blood pressure. Your doctor should check your blood pressure before you start taking teriflunomide tablets and while you are taking teriflunomide tablets. new or worsening breathing problems. These may be serious and lead to death. Call your doctor right away or get emergency medical help if you have shortness of breath or coughing with or without fever. The most common side effects of teriflunomide tablets include: headache diarrhea nausea hair thinning or loss (alopecia) increases in the results of blood tests to check your liver function These are not all the possible side effects of teriflunomide tablets. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store teriflunomide tablets? Store teriflunomide tablets at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Keep teriflunomide tablets and all medicines out of the reach of children. General information about the safe and effective use of teriflunomide tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use teriflunomide tablets for a condition for which it was not prescribed. Do not give teriflunomide tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about teriflunomide tablets that is written for health professionals. What are the ingredients in teriflunomide tablets? Active ingredient: teriflunomide Inactive ingredients in 7 mg and 14 mg tablets: lactose monohydrate, hydroxypropylcellulose, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The film coating for the 7 mg and 14 mg tablet is made of titanium dioxide, talcum, hypromellose, cottonseed oil, and FD & C Blue no. 2 Al-Lake. In addition to these, the 7 mg tablet film coating includes FD & C Yellow No. 5 (tartrazine). The 14 mg tablet includes FD & C Red No. 40. For more information, call SOLA Pharmaceuticals at 1 866-747-7365 Manufactured for: SOLA Pharmaceuticals, Baton Rouge, LA 70810 Manufactured in Malta This Medication Guide has been approved by the U.S. Food and Drug Administration.     Iss. 09/2023

Teriflunomide tablets are available as 7 mg and 14 mg tablets. The 14 mg tablet is a blue (pale blue to pastel blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “14” on one side. Each tablet contains 14 mg of teriflunomide. The 7 mg tablet is a green (light greenish-blue grey to pale greenish-blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “7” on one side. Each tablet contains 7 mg of teriflunomide.

Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis. The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.

Potential to Prolong the QT Interval In a placebo controlled thorough QT study performed in healthy adult subjects, there was no evidence that teriflunomide caused QT interval prolongation of clinical significance (i.e., the upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 ms).

Teriflunomide is the principal active metabolite of leflunomide and is responsible for leflunomide’s activity in vivo . At recommended doses, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide.

Boxed Warning                                                        11/2020 Warnings and Precautions ( 5.1 , 5.6 , 5.7 )                 11/2020 Warnings and Precautions ( 5.11 )                             04/2021

Elimination of teriflunomide can be accelerated by administration of cholestyramine or activated charcoal for 11 days. ( 5.3 ) Teriflunomide tablets may decrease WBC. A recent CBC should be available before starting teriflunomide tablets. Monitor for signs and symptoms of infection. Consider suspending treatment with teriflunomide tablets in case of serious infection. Do not start teriflunomide tablets in patients with active infections. ( 5.4 ) Stop teriflunomide tablets if patient has anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms; initiate rapid elimination. ( 5.3 , 5.5 , 5.6 , 5.7 ) If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing teriflunomide tablets. ( 5.8 ) Teriflunomide tablets may increase blood pressure. Measure blood pressure at treatment initiation and monitor blood pressure during treatment. ( 5.9 )

NDC 70512- 850 -28 Teriflunomide Tablets 7 mg Rx only Dispense the enclosed Medication Guide to each patient. 28 tablets SOLA PHARMACEUTICALS NDC 70512- 850 -28 Teriflunomide Tablets 7 mg Rx only Dispense the enclosed Medication Guide to each patient. 28 tablets SOLA PHARMACEUTICALS USUAL DOSAGE: One tablet orally once daily (see package insert). Each tablet contains 7 mg teriflunomide. Contains FD & C Yellow No. 5 (tartrazine) as a color additive. Teriflunomide tablets can be taken with or without food. Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Keep this and all medication out of reach of children. Manufactured for: SOLA Pharmaceuticals LLC Baton Rouge, LA 70810 Manufactured in Malta Rev.03/2023 GTIN 00370512851289 Lot EXP SN NDC 70512- 851 -28 Teriflunomide Tablets 14 mg Rx only Dispense the enclosed Medication Guide to each patient.

Risk Summary There are no data on the presence of teriflunomide 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 teriflunomide, women should not breastfeed during treatment with teriflunomide tablets.

Pregnancy Testing Exclude pregnancy prior to initiation of treatment with teriflunomide tablets in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.1 )]. Contraception Females Females of reproductive potential should use effective contraception while taking teriflunomide tablets. If teriflunomide tablet is discontinued, use of contraception should be continued until it is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL, the level expected to have minimal fetal risk, based on animal data). Females of reproductive potential who wish to become pregnant should discontinue teriflunomide tablets and undergo an accelerated elimination procedure. Effective contraception should be used until it is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.1 )] . Males Teriflunomide is detected in human semen. Animal studies to specifically evaluate the risk of male mediated fetal toxicity have not been conducted. To minimize any possible risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue use of teriflunomide tablets and either undergo an accelerated elimination procedure or wait until verification that the plasma teriflunomide concentration is less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions ( 5.3 )] .

Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide tablets in the postmarketing setting [see Warnings and Precautions (5.1) ] . Concomitant use of teriflunomide tablets with other hepatotoxic drugs may increase the risk of severe liver injury.  Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets  [see Warnings and Precautions (5.1) ] . If drug induced liver injury is suspected, discontinue teriflunomide tablets and start an accelerated elimination procedure with cholestyramine or charcoal  [see Warnings and Precautions (5.3 )] . Teriflunomide tablet is contraindicated in patients with severe hepatic impairment  [see Contraindications ( 4) ].   Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide tablets. Embryofetal Toxicity Teriflunomide tablet is contraindicated for use in pregnant women and in females 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 tablets in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide tablet treatment and during an accelerated drug elimination procedure after teriflunomide tablet treatment. Stop teriflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant   [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), and Clinical Pharmacology ( 12.3 )]

Teriflunomide tablet is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

The recommended dose of teriflunomide tablets is 7mg or 14 mg orally once daily. Teriflunomide tablets can be taken with or without food. Monitoring to Assess Safety. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablet therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets [see  Warnings and Precautions (5.1) ] . Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide tablets. Further monitoring should be based on signs and symptoms of infection [see Warnings and Precautions (5.4) ] . Prior to initiating teriflunomide tablets, screen patients for latent tuberculosis infection with a tuberculin skin test or blood test for mycobacterium tuberculosis infection [ see Warnings and Precautions (5.4) ] . Exclude pregnancy prior to initiation of treatment with teriflunomide tablets in females of reproductive potential [see  Warnings and Precautions  (5.2) ]. Check blood pressure before start of teriflunomide tablet treatment and periodically thereafter [see  Warnings and Precautions  (5.9 )].

Teriflunomide tablets are available as 7 mg and 14 mg tablets. The 14 mg tablet is a blue (pale blue to pastel blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “14” on one side. Each tablet contains 14 mg of teriflunomide. The 7 mg tablet is a green (light greenish-blue grey to pale greenish-blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “7” on one side. Each tablet contains 7 mg of teriflunomide. Teriflunomide 14 mg tablets are supplied as: NDC 70512-0851-28  Carton of 28 tablets containing 1 wallet composed of 2 folded blister cards of 14 tablets per blister card Teriflunomide 7 mg tablets are supplied as: NDC 70512-0850-28   Carton of 28 tablets containing 1 wallet composed of 2 folded blister cards of 14 tablets per blister card Store at 68°F to 77°F (20°C to 25°C) [see USP Controlled Room Temperature] with excursions permitted between 59°F and 86°F (15°C and 30°C).

Teriflunomide tablet is contraindicated in/with: Patients with severe hepatic impairment [see  Warnings and Precautions  (5.1) ] . Pregnant women and females of reproductive potential not using effective contraception. Teriflunomide tablets may cause fetal harm [see  Warnings and Precautions   (5.2 , 5.3) and  Use in Specific Populations  (8.1) ]. Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablets. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions  (5.5) ]. Co-administration with leflunomide [see  Clinical Pharmacology (12.3) ].

Effect of Teriflunomide Tablets on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . In patients taking teriflunomide tablets, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology ( 12.3 )] .

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). A Medication Guide is required for distribution with teriflunomide tablets. Hepatotoxicity Inform patients that teriflunomide tablets may cause liver injury, which can be life-threatening, and that their liver enzymes will be checked before starting teriflunomide tablets and at least monthly for 6 months after starting teriflunomide tablets [see Dosage and Administration ( 2 ) and Warnings and Precautions ( 5.1 )] . 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. Embryofetal Toxicity Advise females of reproductive potential of the potential for fetal harm if teriflunomide tablets is taken during pregnancy to notify their healthcare provider immediately if a pregnancy occurs or is suspected to use effective contraception during treatment with teriflunomide tablets and until the teriflunomide plasma concentration is verified to be less than 0.02 mg/L [see Warnings and Precautions ( 5.2 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), Clinical Pharmacology ( 12.3 )]. Instruct men taking teriflunomide tablets and not wishing 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 wishing to father a child to discontinue use of teriflunomide tablets and undergo an accelerated elimination procedure. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Teriflunomide during pregnancy [see Use in Specific Populations ( 8.1 , 8.3 ), Clinical Pharmacology ( 12.3 )] . Availability of an Accelerated Elimination Procedure Advise patients that teriflunomide 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 [see Warnings and Precautions ( 5.3 )] . 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 teriflunomide tablets. Inform patients that they may be more likely to get infections when taking teriflunomide tablets and that they should contact their physician if they develop symptoms of infection, particularly in case of fever [see Warnings and Precautions ( 5.4 )] . Advise patients that the use of some vaccines should be avoided during treatment with teriflunomide tablets and for at least 6 months after discontinuation. Hypersensitivity Reactions Advise patients to discontinue teriflunomide tablets and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur [see Contraindications ( 4 ) and Warnings and Precautions ( 5.5 )] . 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 teriflunomide tablets and seek immediate medical attention if any signs of a serious skin reaction, such as SJS or TEN,occur [see Warnings and Precautions ( 5.6 )] . Signs and symptoms can include rash, mouth sores, blisters, or peeling skin. DRESS/Multi-organ Hypersensitivity Instruct patients and caregivers that a fever or rash associated with signs of other organ system involvement (e.g., lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately. Teriflunomide tablets should be discontinued immediately if a serious hypersensitivity reaction is suspected [see Warnings and Precautions ( 5.7 )] . Peripheral Neuropathy 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 [see Warnings and Precautions ( 5.8 )] . Increased Blood Pressure Inform patients that teriflunomide tablets may increase blood pressure [see Warnings and Precautions ( 5.9 )] . Lactation Advise females not to breastfeed during treatment with teriflunomide tablets [see Use in Specific Populations ( 8.2 )] . Manfuactured for: Sola Pharmaceuticals LLC Baton Rouge, LA 70810 Manufactured in Malta Iss.  09/2023 Medication Guide Teriflunomide (ter” i floo’ noe mide) Tablets, for oral use

Safety and effectiveness in pediatric patients have not been established.   Pancreatitis has been reported in adults in the postmarketing setting, but appears to occur at higher frequency in the pediatric population [see Warnings and Precautions ( 5.11 ) ] .  Additionally, elevated or abnormal blood creatine phosphokinase was reported. Juvenile Animal Toxicity Data Oral administration of teriflunomide (0, 0.3, 3, or 6 mg/kg/day) to young rats on postnatal days 21 to 70 resulted in suppression of immune function (T-cell dependent antibody response) at the mid and high doses, and adverse effects on male reproductive organs (reduced sperm count) and altered neurobehavioral function (increased locomotor activity) at the high dose. Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Sanofi-Aventis U.S. LLC’s Aubagio ® (teriflunomide) tablets.  However, due to Sanofi-Aventis U.S. LLC’s marketing exclusivity rights, this drug product is not labeled with that information.

Clinical studies of teriflunomide tablets did not include patients over 65 years old.

Carcinogenesis No evidence of carcinogenicity was observed in lifetime carcinogenicity bioassays in mouse and rat. In mouse, teriflunomide was administered orally at doses up to 12 mg/kg/day for up to 95 to 104 weeks; plasma teriflunomide exposures (AUC) at the highest dose tested are approximately 3 times that in humans at the maximum recommended human dose (MRHD, 14 mg/day). In rat, teriflunomide was administered orally at doses up to 4 mg/kg/day for up to 97 to 104 weeks; plasma teriflunomide AUCs at the highest doses tested are less than that in humans at the MRHD. Mutagenesis Teriflunomide was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro HPRT assay, and in in vivo micronucleus and chromosomal aberration assays. Teriflunomide was positive in an in vitro chromosomal aberration assay in human lymphocytes, with and without metabolic activation. Addition of uridine (to supplement the pyrimidine pool) reduced the magnitude of the clastogenic effect; however, teriflunomide was positive in the in vitro chromosomal aberration assay, even in the presence of uridine. 4-Trifluoromethylaniline (4-TFMA), a minor metabolite of teriflunomide, was positive in the in vitro bacterial reverse mutation (Ames) assay, the in vitro HPRT assay, and the in vitro chromosomal aberration assay in mammalian cells. 4-TFMA was negative in in vivo micronucleus and chromosomal aberration assays. Impairment of Fertility Oral administration of teriflunomide (0, 1, 3, 10 mg/kg/day) to male rats prior to and during mating (to untreated females) resulted in no adverse effects on fertility; however, reduced epididymal sperm count was observed at the mid and high doses tested. The no-effect dose for reproductive toxicity in male rats (1 mg/kg) is less than the MRHD on a mg/m 2 basis. Oral administration of teriflunomide (0, 0.84, 2.6, 8.6 mg/kg/day) to female rats, prior to and during mating (to untreated males) and continuing to gestation day 6, resulted in embryolethality, reduced fetal body weight, and/or malformations at all doses tested. Due to marked embryolethality at the highest dose tested, no fetuses were available for evaluation. The lowest dose tested is less than the MRHD on a mg/m 2 basis.

The following serious adverse reactions are described elsewhere in the prescribing information: Hepatotoxicity [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Bone Marrow Effects/Immunosuppression Potential/Infections [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions  [see Contraindications ( 4 ) and Warnings and Precautions ( 5.5 )] Serious Skin Reactions [see Warnings and Precautions ( 5.6 )] Drug Reaction with Eosinophilia and Systemic Symptoms  [see Warnings and Precautions ( 5.7 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.8 )] Increased Blood Pressure [see Warnings and Precautions ( 5.9 )] Respiratory Effects [see Warnings and Precautions ( 5.10) ] Pancreatitis in Pediatric Patients [ see Warnings and Precautions ( 5.11 ) ]

There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects. In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions ( 5.3 )] .

Teriflunomide is an oral de novo pyrimidine synthesis inhibitor of the DHO-DH enzyme, with the chemical name (Z)-2-Cyano-3-hydroxy-but-2-enoic acid-(4­ trifluoromethylphenyl)-amide. Its molecular weight is 270.21, and the empirical formula is C 12 H 9 F 3 N 2 O 2 with the following chemical structure: Teriflunomide is a white to almost white powder that is sparingly soluble in acetone, slightly soluble in polyethylene glycol and ethanol, very slightly soluble in isopropanol and practically insoluble in water. Teriflunomide is formulated as film-coated tablets for oral administration. Teriflunomide tablets contain 7 mg and 14 mg of teriflunomide and the following inactive ingredients: lactose monohydrate, hydroxypropylcellulose, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The film coating for the 7mg and 14mg tablets is made of hypromellose, hydroxypropylcellulose, cottonseed oil, talcum, titanium dioxide, and FD & C Blue no. 2 Al-Lake. In addition to these, the 7mg tablet film coating includes FD & C Yellow no. 5 (tartrazine). The 14mg tablet includes FD & C Red no. 40.

Four randomized, controlled, double-blind clinical trials established the efficacy of teriflunomide tablets in patients with relapsing forms of multiple sclerosis. Study 1 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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 one relapse over the year preceding the trial or at least two relapses over the two years preceding the trial. Patients were required not to have received interferon-beta for at least four months, or any other multiple sclerosis medication for at least six months before entering the study, nor were these medications permitted during the study. Neurological evaluations were to be performed at screening, every 12 weeks until week 108, and after suspected relapses. MRI was to be performed at screening, and at Week 24, 48, 72, and 108. The primary endpoint was the annualized relapse rate (ARR). In Study 1, 1088 patients were randomized to receive teriflunomide tablets 7 mg (n=366), teriflunomide tablets 14 mg (n=359), or placebo (n=363). At entry, patients had an Expanded Disability Status Scale (EDSS) score ≤5.5. Patients had a mean age of 38 years, mean disease duration of 5 years, and mean EDSS at baseline of 2.7. A total of 91% of patients had relapsing remitting multiple sclerosis, and 9% had a progressive form of multiple sclerosis with relapses. The mean duration of treatment was 635, 627, and 631 days for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. The percentage of patients who completed the study treatment period was 75%, 73%, and 71% for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. There was a statistically significant reduction in ARR for patients who received teriflunomide tablets 7 mg or teriflunomide tablets 14 mg, compared to patients who received placebo (see Table 2 ). 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 teriflunomide tablets 14 mg group compared to placebo (see Table 2 and Figure 1 ). The effect of teriflunomide tablets 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 teriflunomide tablets 7 mg and teriflunomide tablets 14 mg groups than in the placebo group. Patients in both teriflunomide tablets groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than those in the placebo group (see Table 2 ). Table 2:  Clinical and MRI Results of Study 1   Teriflunomide Tablets 7 mg N=365 Teriflunomide Tablets 14 mg N=358 Placebo N=363 1 Total lesion volume: sum of T2 and hypointense T1 lesion volume in mL 2 p-values based on cubic root transformed data for total lesion volume Clinical Endpoints Annualized relapse rate 0.370 (p=0.0002) 0.369 (p=0.0005) 0.539 Relative risk reduction 31% 31% – Percent of patients remaining relapse-free at week 108 53.7% 56.5% 45.6% Percent disability progression at week 108 21.7% (p=0.084) 20.2% (p=0.028) 27.3% Hazard ratio 0.76 0.70 – MRI Endpoints Median change from baseline in Total lesion volume 1 (mL) at week 108 0.755 (p=0.0317) 2 0.345 (p=0.0003) 2 1.127 Mean number of Gd-enhancing T1-lesions per scan 0.570 (p < 0.0001) 0.261 (p < 0.0001) 1.331 Study 2 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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 one relapse over the year preceding the trial, or at least two relapses over the two years preceding the trial. Patients were required not to have received any multiple sclerosis medication for at least three months before entering the trial, nor were these medications permitted during the trial. Neurological evaluations were to be performed at screening, every 12 weeks until completion, and after every suspected relapse. The primary end point was the ARR. A total of 1165 patients received teriflunomide tablets 7 mg (n=407), teriflunomide tablets 14 mg (n=370), or placebo (n=388). Patients had a mean age of 38 years, a mean disease duration of 5 years, and a mean EDSS at baseline of 2.7. A total of 98% of patients had relapsing remitting multiple sclerosis, and 2% had a progressive form of multiple sclerosis with relapses. The mean duration of treatment was 552, 567, and 571 days for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. The percentage of patients who completed the study treatment period was 67%, 66%, and 68% for teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo, respectively. There was a statistically significant reduction in the ARR for patients who received teriflunomide tablets 7 mg or teriflunomide tablets 14 mg compared to patients who received placebo (see Table 3 ). 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 teriflunomide tablets 14 mg group compared to placebo (see Table 3 and Figure 2 ). Table 3: Clinical Results of Study 2   Teriflunomide Tablets 7 mg N=407 Teriflunomide Tablets 14 mg N=370 Placebo N=388 Clinical Endpoints Annualized relapse rate 0.389 (p=0.0183) 0.319 (p=0.0001) 0.501 Relative risk reduction 22% 36% – Percent of patients remaining relapse-free at week 108 58.2% 57.1% 46.8% Percent disability progression at week 108 21.1% (p=0.762) 15.8% (p=0.044) 19.7% Hazard ratio 0.96 0.69 – Study 3 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of teriflunomide tablets 7 mg and teriflunomide tablets 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. A total of 614 patients received teriflunomide tablets 7 mg (n=203), teriflunomide tablets 14 mg (n=214), or placebo (n=197). Patients had a mean age of 32 years, EDSS at baseline of 1.7, and mean disease duration of two months. The proportion of patients free of relapse was greater in the teriflunomide tablets 7 mg (70.5%, p < 0.05) and teriflunomide tablets 14 mg (72.2%, p < 0.05) groups than in the placebo group (61.7%). The effect of teriflunomide tablets on MRI activity was also demonstrated in Study 4, a randomized, double-blind, placebo-controlled clinical trial of multiple sclerosis patients with relapse. In Study 4, MRI 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 teriflunomide tablets 7 mg (n=61), teriflunomide tablets 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 teriflunomide tablets 7 mg (1.06) and teriflunomide tablets 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).

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Teriflunomide during pregnancy. Healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2. Risk Summary Teriflunomide tablet 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 [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . In animal reproduction studies in rat and rabbit, 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 [see Data ] . 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 [see Clinical Considerations and Data ] . There are no human data pertaining to exposures later in the first trimester or beyond. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. Clinical Considerations Fetal/Neonatal adverse reactions Lowering the plasma concentration of teriflunomide by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease the risk to the fetus from teriflunomide tablets. The accelerated drug elimination procedure includes verification that the plasma teriflunomide concentration is less than 0.02 mg/L [see Warnings and Precautions ( 5.3 ) and Clinical Pharmacology ( 12.3 )]. Data Human data Available human data are limited. Prospectively reported data (from clinical trials and postmarketing reports) from > 150 pregnancies in patients treated with teriflunomide tablets and > 300 pregnancies in patients treated with leflunomide have not demonstrated an increased rate of congenital malformations or miscarriage following teriflunomide exposure in the early first trimester when followed by an accelerated elimination procedure. Specific patterns of major congenital malformations in humans have not been observed. Limitations of these data include an inadequate number of reported pregnancies from which to draw conclusions, the short duration of drug exposure in reported pregnancies, which precludes a full evaluation of the fetal risks, incomplete reporting, and the inability to control for confounders (such as underlying maternal disease and use of concomitant medications). Animal data When teriflunomide (oral doses of 1, 3, or 10 mg/kg/day) was administered to pregnant rats throughout the period of organogenesis, high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death were observed at doses not associated with maternal toxicity. Adverse effects on fetal development were observed following dosing at various stages throughout organogenesis. Maternal plasma exposure at the no-effect level (1.0 mg/kg/day) for fetal developmental toxicity in rats was less than that in humans at the maximum recommended human dose (MRHD, 14 mg/day). Administration of teriflunomide (oral doses of 1, 3.5, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death at doses associated with minimal maternal toxicity. Maternal plasma exposure at the no-effect dose (1.0 mg/kg/day) for fetal developmental toxicity in rabbits was less than that in humans at the MRHD. In studies in which teriflunomide (oral doses of 0.05, 0.1, 0.3, 0.6, or 1.0 mg/kg/day) was administered to rats during gestation and lactation, decreased growth, eye and skin abnormalities, and high incidences of malformation (limb defects) and postnatal death were observed in the offspring at doses not associated with maternal toxicity. Maternal plasma exposure at the no-effect dose for prenatal and postnatal developmental toxicity in rats (0.10 mg/kg/day) was less than that in humans at the MRHD. In animal reproduction studies of leflunomide, embryolethality and teratogenic effects were observed in pregnant rat and rabbit at or below clinically relevant plasma teriflunomide exposures (AUC). In published reproduction studies in pregnant mice, leflunomide was embryolethal and increased the incidence of malformations (craniofacial, axial skeletal, heart and great vessel). Supplementation with exogenous uridine reduced the teratogenic effects in pregnant mice, suggesting that the mode of action (inhibition of mitochondrial enzyme dihydroorotate dehydrogenase) is the same for therapeutic efficacy and developmental toxicity. At recommended doses in humans, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide.

Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide tablets in the postmarketing setting. Patients with pre-existing liver disease and patients taking other hepatotoxic drugs may be at increased risk for developing liver injury when taking teriflunomide tablets. Clinically significant liver injury can occur at any time during treatment with teriflunomide tablets. Patients with pre-existing acute or chronic liver disease, or those with serum alanine  aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with teriflunomide tablets. Teriflunomide tablets is contraindicated in patients with severe hepatic impairment [see  Contraindications   (4) ] . In placebo-controlled trials in adult patients, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving teriflunomide tablets 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment. Half of the cases returned to normal without drug discontinuation. In clinical trials, if ALT elevation was greater than three times the ULN on two consecutive tests, teriflunomide tablet was discontinued and patients underwent an accelerated elimination procedure [see Warnings and Precautions (5.3)] . Of the patients who underwent discontinuation and accelerated elimination in controlled trials, half returned to normal or near normal values within 2 months. One patient in the controlled trials in adult patients developed ALT 32 times the ULN and jaundice 5 months after initiation of teriflunomide tablets 14 mg treatment. The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure. Teriflunomide-induced liver injury in this patient could not be ruled out. Obtain serum transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablet therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets. Consider additional monitoring when teriflunomide tablet is given with other potentially hepatotoxic drugs. Consider discontinuing teriflunomide tablets if serum transaminase increase (greater than three times the ULN) is confirmed. Monitor serum transaminase and bilirubin on teriflunomide tablet therapy, particularly in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. If liver injury is suspected to be teriflunomide-induced, discontinue teriflunomide tablets and start an accelerated elimination procedure [see  Warnings and Precautions   (5.3) ] and monitor liver tests weekly until normalized. If teriflunomide-induced liver injury is unlikely because some other probable cause has been found, resumption of teriflunomide tablet therapy may be considered.

Read this Medication Guide before you start using teriflunomide tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about teriflunomide tablets? Teriflunomide tablets may cause serious side effects, including: Liver problems: Teriflunomide tablets may cause serious liver problems, including liver failure that can be life-threatening and may require a liver transplant. Your risk of developing serious liver problems may be higher if you already have liver problems or take other medicines that also affect your liver. Your doctor should do blood tests to check your liver: within 6 months before you start taking teriflunomide tablets 1 time a month for 6 months after you start taking teriflunomide tablets Call your doctor right away if you have any of the following symptoms of liver problems: nausea vomiting stomach pain loss of appetite tiredness your skin or the whites of your eyes turn yellow dark urine Harm to your unborn baby: Teriflunomide tablets may cause harm to your unborn baby. Do not take teriflunomide tablets if you are pregnant. Do not take teriflunomide tablets unless you are using effective birth control. If you are a female, you should have a pregnancy test before you start taking teriflunomide tablets. Use effective birth control during your treatment with teriflunomide tablets. After stopping teriflunomide tablets, continue using effective birth control until you have blood tests to make sure your blood levels of teriflunomide are low enough. If you become pregnant while taking teriflunomide tablets or within 2 years after you stop taking it, tell your doctor right away. Teriflunomide Tablets Pregnancy Registry. If you become pregnant while taking Teriflunomide or during the 2 years after you stop taking Teriflunomide, talk to your doctor about enrolling in the Teriflunomide Pregnancy Registry at 1-800-745-4447, option 2. The purpose of this registry is to collect information about your health and your baby’s health. For men taking teriflunomide tablets: If your female partner plans to become pregnant, you should stop taking teriflunomide tablets and ask your doctor how to quickly lower the levels of teriflunomide in your blood. If your female partner does not plan to become pregnant, you and your female partner should use effective birth control during your treatment with teriflunomide tablets. Teriflunomide remains in your blood after you stop taking it, so continue using effective birth control until teriflunomide blood levels have been checked and they are low enough. Teriflunomide may stay in your blood for up to 2 years after you stop taking it. Your doctor can prescribe a medicine to help lower your blood levels of teriflunomide more quickly. Talk to your doctor if you want more information about this. What is Teriflunomide Tablet? Teriflunomide tablet is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is not known if teriflunomide tablet is safe and effective in children. Who should not take teriflunomide tablets? Do not take teriflunomide tablets if you: have severe liver problems are pregnant or are of childbearing age and not using effective birth control have had an allergic reaction to leflunomide, teriflunomide, or any other ingredients in teriflunomide tablets. Please see the end of this Medication Guide for a complete list of ingredients in teriflunomide. take a medicine called leflunomide What should I tell my doctor before taking teriflunomide tablets? Before you take teriflunomide tablets, tell your doctor about all of your medical conditions, including if you: have liver or kidney problems have a fever or infection, or you are unable to fight infections have numbness or tingling in your hands or feet that is different from your MS symptoms have diabetes have had serious skin problems when taking other medicines have breathing problems have high blood pressure are breastfeeding or plan to breastfeed. It is not known if teriflunomide passes into your breast milk. You and your doctor should decide if you will take teriflunomide tablets or breastfeed. You should not do both. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using teriflunomide tablets and other medicines may affect each other causing serious side effects. Teriflunomide tablets may affect the way other medicines work, and other medicines may affect how teriflunomide tablets work. Especially tell your doctor if you take medicines that could raise your chance of getting infections, including medicines used to treat cancer or to control your immune system. Ask your doctor or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine. How should I take teriflunomide tablets? Take teriflunomide tablets exactly as your doctor tells you to take it. Take teriflunomide tablets 1 time each day. Take teriflunomide tablets with or without food. What are possible side effects of teriflunomide tablets? Teriflunomide tablets may cause serious side effects, including: see “ What is the most important information I should know about teriflunomide tablets? ” decreases in your white blood cell count. Your white blood cell counts should be checked before you start taking teriflunomide tablets. When you have a low white blood cell count you: may have more frequent infections. You should have a skin test for TB (tuberculosis) before you start taking teriflunomide tablets. Tell your doctor if you have any of these symptoms of an infection: fever tiredness body aches chills nausea vomiting should not receive certain vaccinations during your treatment with teriflunomide tablets and for 6 months after your treatment with teriflunomide tablets ends. allergic reactions. Stop taking teriflunomide tablets and call your doctor right away or get emergency medical help if you have difficulty breathing , itching, swelling on any part of your body including in your lips, eyes, throat, or tongue. serious skin reactions. Teriflunomide tablets may cause serious skin reactions that may lead to death. Stop taking teriflunomide tablets and call your doctor right away or get emergency medical help if you have any of the following symptoms: rash or redness and peeling, mouth sores or blisters. other types of allergic reactions or serious problems that may affect different parts of the body such as your liver, kidneys, heart, or blood cells. You may or may not have a rash with these types of reactions. Other symptoms you may have are: severe muscle pain swollen lymph glands swelling of your face unusual bruising or bleeding weakness or tiredness yellowing of your skin or the white part of your eyes If you have a fever or rash with any of the above symptoms, stop taking teriflunomide and call your doctor right away. numbness or tingling in your hands or feet that is different from your MS symptoms. You have a higher chance of getting these symptoms if you: are over 60 years of age take certain medicines that affect your nervous system have diabetes Tell your doctor if you have numbness or tingling in your hands or feet that is different from your MS. high blood pressure. Your doctor should check your blood pressure before you start taking teriflunomide tablets and while you are taking teriflunomide tablets. new or worsening breathing problems. These may be serious and lead to death. Call your doctor right away or get emergency medical help if you have shortness of breath or coughing with or without fever. The most common side effects of teriflunomide tablets include: headache diarrhea nausea hair thinning or loss (alopecia) increases in the results of blood tests to check your liver function These are not all the possible side effects of teriflunomide tablets. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store teriflunomide tablets? Store teriflunomide tablets at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Keep teriflunomide tablets and all medicines out of the reach of children. General information about the safe and effective use of teriflunomide tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use teriflunomide tablets for a condition for which it was not prescribed. Do not give teriflunomide tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for information about teriflunomide tablets that is written for health professionals. What are the ingredients in teriflunomide tablets? Active ingredient: teriflunomide Inactive ingredients in 7 mg and 14 mg tablets: lactose monohydrate, hydroxypropylcellulose, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The film coating for the 7 mg and 14 mg tablet is made of titanium dioxide, talcum, hypromellose, cottonseed oil, and FD & C Blue no. 2 Al-Lake. In addition to these, the 7 mg tablet film coating includes FD & C Yellow No. 5 (tartrazine). The 14 mg tablet includes FD & C Red No. 40. For more information, call SOLA Pharmaceuticals at 1 866-747-7365 Manufactured for: SOLA Pharmaceuticals, Baton Rouge, LA 70810 Manufactured in Malta This Medication Guide has been approved by the U.S. Food and Drug Administration.     Iss. 09/2023

Teriflunomide tablets are available as 7 mg and 14 mg tablets. The 14 mg tablet is a blue (pale blue to pastel blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “14” on one side. Each tablet contains 14 mg of teriflunomide. The 7 mg tablet is a green (light greenish-blue grey to pale greenish-blue) colored, round, biconvex, film-coated tablet debossed with the dose strength “7” on one side. Each tablet contains 7 mg of teriflunomide.

Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis. The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.

Potential to Prolong the QT Interval In a placebo controlled thorough QT study performed in healthy adult subjects, there was no evidence that teriflunomide caused QT interval prolongation of clinical significance (i.e., the upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 ms).

Teriflunomide is the principal active metabolite of leflunomide and is responsible for leflunomide’s activity in vivo . At recommended doses, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide.

Boxed Warning                                                        11/2020 Warnings and Precautions ( 5.1 , 5.6 , 5.7 )                 11/2020 Warnings and Precautions ( 5.11 )                             04/2021

Elimination of teriflunomide can be accelerated by administration of cholestyramine or activated charcoal for 11 days. ( 5.3 ) Teriflunomide tablets may decrease WBC. A recent CBC should be available before starting teriflunomide tablets. Monitor for signs and symptoms of infection. Consider suspending treatment with teriflunomide tablets in case of serious infection. Do not start teriflunomide tablets in patients with active infections. ( 5.4 ) Stop teriflunomide tablets if patient has anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms; initiate rapid elimination. ( 5.3 , 5.5 , 5.6 , 5.7 ) If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing teriflunomide tablets. ( 5.8 ) Teriflunomide tablets may increase blood pressure. Measure blood pressure at treatment initiation and monitor blood pressure during treatment. ( 5.9 )

NDC 70512- 850 -28 Teriflunomide Tablets 7 mg Rx only Dispense the enclosed Medication Guide to each patient. 28 tablets SOLA PHARMACEUTICALS NDC 70512- 850 -28 Teriflunomide Tablets 7 mg Rx only Dispense the enclosed Medication Guide to each patient. 28 tablets SOLA PHARMACEUTICALS USUAL DOSAGE: One tablet orally once daily (see package insert). Each tablet contains 7 mg teriflunomide. Contains FD & C Yellow No. 5 (tartrazine) as a color additive. Teriflunomide tablets can be taken with or without food. Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Keep this and all medication out of reach of children. Manufactured for: SOLA Pharmaceuticals LLC Baton Rouge, LA 70810 Manufactured in Malta Rev.03/2023 GTIN 00370512851289 Lot EXP SN NDC 70512- 851 -28 Teriflunomide Tablets 14 mg Rx only Dispense the enclosed Medication Guide to each patient.

Risk Summary There are no data on the presence of teriflunomide 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 teriflunomide, women should not breastfeed during treatment with teriflunomide tablets.

Pregnancy Testing Exclude pregnancy prior to initiation of treatment with teriflunomide tablets in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.1 )]. Contraception Females Females of reproductive potential should use effective contraception while taking teriflunomide tablets. If teriflunomide tablet is discontinued, use of contraception should be continued until it is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL, the level expected to have minimal fetal risk, based on animal data). Females of reproductive potential who wish to become pregnant should discontinue teriflunomide tablets and undergo an accelerated elimination procedure. Effective contraception should be used until it is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.1 )] . Males Teriflunomide is detected in human semen. Animal studies to specifically evaluate the risk of male mediated fetal toxicity have not been conducted. To minimize any possible risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue use of teriflunomide tablets and either undergo an accelerated elimination procedure or wait until verification that the plasma teriflunomide concentration is less than 0.02 mg/L (0.02 mcg/mL) [see Warnings and Precautions ( 5.3 )] .