Drug Safety-related Labeling Changes (SrLC)

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AUBAGIO (NDA-202992)

(TERIFLUNOMIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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04/30/2021 (SUPPL-15)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hepatotoxicity

(Additions and/or revisions underlined)

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 AUBAGIO 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. . .

One patient in the controlled trials in adult patients developed ALT 32 times the ULN and jaundice 5 months after initiation of AUBAGIO 14 mg treatment.

5.11 Pancreatitis in Pediatric Patients

(Newly added section)

AUBAGIO is not approved for use in pediatric patients. In the pediatric clinical trial, cases of pancreatitis were observed in 1.8% (2/109) of patients receiving AUBAGIO; one of these cases was serious [see Use in Specific Populations (8.4)]. If pancreatitis is suspected, discontinue teriflunomide and start an accelerated elimination procedure [see Warnings and Precautions (5.3)].

5.4 Bone Marrow Effects/Immunosuppression Potential/Infections

(Additions and/or revisions underlined)

Bone Marrow Effects

A mean decrease compared to baseline in white blood cell (WBC) count of approximately 15% (mainly neutrophils and lymphocytes) and in platelet count of approximately 10% was observed in placebo-controlled trials in adult patients with 7 mg and 14 mg of AUBAGIO. The decrease in mean WBC count occurred during the first 6 weeks and WBC count remained low during treatment. In placebo-controlled studies in adult patients, neutrophil count <1.5 × 109/L was observed in 12% and 16% of patients receiving AUBAGIO 7 mg and 14 mg, respectively, compared with 7% of patients receiving placebo; lymphocyte count <0.8 × 109/L was observed in 10% and 12% of patients receiving AUBAGIO 7 mg and 14 mg, respectively, compared with 6% of patients receiving placebo.

Risk of Infection/Tuberculosis Screening

In placebo-controlled studies of AUBAGIO in adult patients, no overall increase in the risk of serious infections was observed with AUBAGIO 7 mg (2.2%) or 14 mg (2.7%) compared to placebo (2.2%). . .

In clinical studies with AUBAGIO in adult patients, cases of tuberculosis have been observed. Prior to initiating AUBAGIO, screen patients for latent tuberculosis infection with a tuberculin skin test or with a blood test for mycobacterium tuberculosis infection.

5.8 Peripheral Neuropathy

(Additions and/or revisions underlined)

In placebo-controlled studies in adult patients, peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), occurred more frequently in patients taking AUBAGIO than in patients taking placebo.

5.9 Increased Blood Pressure

(Additions and/or revisions underlined)

In placebo-controlled studies in adult patients, the mean change from baseline to the end of study in systolic blood pressure was +2.3 mmHg and +2.7 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.6 mmHg for placebo.

In placebo-controlled studies in adult patients, the mean change from baseline to the end of study in systolic blood pressure was +2.3 mmHg and +2.7 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.6 mmHg for placebo.

6 Adverse Reactions

(Additions and/or revisions underlined)

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)]

6.1 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during postapproval use of AUBAGIO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Blood and Lymphatic System Disorders: Thrombocytopenia [see Warnings and Precautions (5.4)]

• Gastrointestinal Disorders: Pancreatitis, colitis

• Hepatobiliary Disorders: Drug-induced liver injury (DILI) [see Warnings and Precautions (5.1)]

• Immune System Disorders: Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema [see Warnings and Precautions (5.5)]

• Respiratory, Thoracic, and Mediastinal Disorders: Interstitial lung disease [see Warnings and Precautions (5.10)]

• Skin and Subcutaneous Tissue Disorders: Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome [see Warnings and Precautions (5.6)]; drug reaction with eosinophilia and systemic symptoms (DRESS) [see Warnings and Precautions (5.7)]; psoriasis or worsening of psoriasis (including pustular psoriasis and nail psoriasis); nail disorders

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions underlined)

Safety and effectiveness in pediatric patients have not been established. Effectiveness of AUBAGIO for the treatment of relapsing form of multiple sclerosis in pediatric patients (10 to 17 years of age) was not established in an adequate and well-controlled clinical study in 166 patients (109 patients received once daily doses of AUBAGIO and 57 patients received placebo) for up to 96 weeks.

Pancreatitis has been reported in adults in the postmarketing setting, but appears to occur at higher frequency in the pediatric population. In this pediatric study, cases of pancreatitis were reported in 1.8% (2/109) of patients who received AUBAGIO compared to no patients in the placebo group. All patients in the pediatric trial recovered or were recovering after treatment discontinuation and accelerated elimination procedure [see Warnings and Precautions (5.11)].

Additionally, elevated or abnormal blood creatine phosphokinase was reported in 6.4% of pediatric patients who received AUBAGIO compared to no patients in the placebo group.

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. At the no-effect dose (0.3 mg/kg/day) for developmental toxicity in juvenile rats, plasma exposures were less than those in pediatric patients at the doses of AUBAGIO tested in the clinical study.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

(Additions and/or revisions underlined)

AUBAGIO may cause serious side effects, including:

• allergic reactions. Stop taking AUBAGIO 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.

If you have a fever or rash with any of the above symptoms, stop taking AUBAGIO and call your doctor right away.

11/06/2020 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hepatotoxicity

(Additions and/or revisions underlined)

Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with AUBAGIO 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 AUBAGIO. Clinically significant liver injury can occur at any time during treatment with AUBAGIO.

5.5 Hypersensitivity Reactions

(Section title revised)

(Additions and/or revisions underlined)

AUBAGIO can cause anaphylaxis and severe allergic reactions [see Contraindications (4)]. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.

Inform patients of the signs and symptoms of anaphylaxis and angioedema.

5.6 Serious Skin Reactions

(Additions and/or revisions underlined)

Cases of serious skin reactions, sometimes fatal, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) [see Warnings and Precautions (5.7)], have been reported with AUBAGIO. Fatal outcomes were reported in one case of TEN and one case of DRESS.

Inform patients of the signs and symptoms that may signal a serious skin reaction. Instruct patients to discontinue AUBAGIO and seek immediate medical care should these signs and symptoms occur. Unless the reaction is clearly not drug related, discontinue AUBAGIO and begin an accelerated elimination procedure immediately [see Warnings and Precautions (5.3)]. In such cases, patients should not be re-exposed to teriflunomide [see Contraindications (4)].

5.7 Drug Reaction with Eosinophilia and Systemic Symptoms

(Additions and/or revisions underlined)

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with AUBAGIO. One fatal case of DRESS that occurred in close temporal association (34 days) with the initiation of AUBAGIO treatment has been reported in the postmarketing setting. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately.

Discontinue AUBAGIO, unless an alternative etiology for the signs or symptoms is established, and begin an accelerated elimination procedure immediately [see Warnings and Precautions (5.3)]. In such cases, patients should not be re-exposed to teriflunomide [see Contraindications (4)].

6 Adverse Reactions

(Newly added information)

• Serious Skin Reactions [see Warnings and Precautions (5.6)]

• Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions (5.7)]

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during postapproval use of AUBAGIO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Drug-induced liver injury (DILI) [see Warnings and Precautions (5.1)]

• Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema

[see Warnings and Precautions (5.5)]

• Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome

[see Warnings and Precautions (5.6)]

• Drug reaction with eosinophilia and systemic symptoms (DRESS) [see Warnings and Precautions (5.7)]

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

(Extensive changes; please refer to label)

Patient Counseling Information

(Extensive changes; please refer to label)

02/28/2020 (SUPPL-10)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Addition of the following bullet:

• Psoriasis or worsening of psoriasis (including pustular psoriasis)

09/06/2019 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Bone Marrow Effects/Immunosuppression Potential/Infections

(Additions and/or revisions are underlined)

Risk of Infection/Tuberculosis Screening

However, one fatal case of klebsiella pneumonia sepsis occurred in a patient taking AUBAGIO 14 mg for 1.7 years. Fatal infections have been reported in the postmarketing setting in patients receiving leflunomide, especially Pneumocystis jirovecii pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid disease, may predispose patients to infection. In clinical studies with AUBAGIO, cytomegalovirus hepatitis reactivation has been observed.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

(Additions and/or revisions are underlined)

What is AUBAGIO?

AUBAGIO 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.

07/24/2019 (SUPPL-6)

Approved Drug Label (PDF)

Boxed Warning

(newly added information)

• Embryofetal Toxicity

AUBAGIO 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 AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant.

5 Warnings and Precautions

5.2 Embryofetal Toxicity

(renaming of subsection with newly added information)

AUBAGIO may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryofetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum recommended human dose (MRHD) of 14 mg/day.

AUBAGIO is contraindicated for use in pregnant women and in females of reproductive potential not using effective contraception. Exclude pregnancy before starting treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. If a woman becomes pregnant while taking AUBAGIO, stop treatment with AUBAGIO, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve a plasma teriflunomide concentration of less than 0.02 mg/L.

Upon discontinuing AUBAGIO, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving AUBAGIO treatment who wish to become pregnant must discontinue AUBAGIO and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL). Men wishing to father a child should also discontinue use of AUBAGIO 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).  Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryofetal risk.

8 Use in Specific Populations

8.1 Pregnancy

(additions are underlined)

Risk Summary

AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of the potential for fetal harm based on animal data.

In animal reproduction studies 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. 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%-4% and 15%-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 AUBAGIO. The accelerated drug elimination procedure includes verification that the plasma teriflunomide concentration is less than 0.02 mg/L .

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 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).

8.2 Lactation

(additions are underlined)

Risk Summary

There are no data on the presence of AUBAGIO in human milk, the effects on the breastfed infant, or the effects on milk production. Teriflunomide was detected in rat milk following a single oral dose. Because of the potential for adverse reactions in a breastfed infant from AUBAGIO, women should not breastfeed during treatment with AUBAGIO.

8.3 Females and Males of Reproductive Potential

(additions are underlined)

Pregnancy Testing

Exclude pregnancy prior to initiation of treatment with AUBAGIO in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment.

Contraception

Females

Females of reproductive potential should use effective contraception while taking AUBAGIO. If AUBAGIO 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 AUBAGIO and undergo of 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).

Males

AUBAGIO 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 AUBAGIO 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).

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(additions are underlined)

Embryofetal Toxicity

Advise females of reproductive potential

• Of the potential for fetal harm if AUBAGIO is taken during pregnancy

• To notify their healthcare provider immediately if a pregnancy occurs or is suspected

• To use effective contraception during treatment with AUBAGIO and until the teriflunomide plasma concentration is verified to be less than 0.02 mg/L

• Instruct men taking AUBAGIO 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 AUBAGIO and undergo an accelerated elimination procedure.

Lactation

Advise females not to breastfeed during treatment with AUBAGIO.

11/29/2016 (SUPPL-2)

Approved Drug Label (PDF)

Boxed Warning

(additions and/or revisions are underlined)

• Risk of Teratogenicity

  AUBAGIO is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant.

4 Contraindications

(additions and/or revisions are underlined)

• Pregnant women and females of reproductive potential not using effective contraception.

5 Warnings and Precautions

5.2 Teratogenicity

(additions and/or revisions are underlined)

AUBAGIO may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-fetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum human recommended dose (MHRD) of 14 mg/day.

AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AUBAGIO during pregnancy. Healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2.

Risk Summary

AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of the potential for fetal harm based on animal data. Human data are not available at this time to inform the presence or absence of drug-associated risk with the use of AUBAGIO during pregnancy.

In animal reproduction studies in rat and rabbits, oral administration of teriflunomide during organogenesis caused teratogenicity and embryolethality at plasma exposures (AUC) lower than that at the maximum human recommended dose (MHRD) of 14 mg/day.

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown.

Clinical Considerations

Women who wish to become pregnant should discontinue use of AUBAGIO and undergo an accelerated elimination procedure to decrease the plasma concentration of teriflunomide to less than 0.02 mg/L (0.02 mcg/mL). Effective contraception should be used until is it verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL). Human plasma concentrations of teriflunomide less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryofetal risk.

If the patient becomes pregnant while taking this drug, stop treatment with AUBAGIO, inform the patient of the potential risk to the fetus, and perform the accelerated drug elimination procedure to achieve plasma concentrations of less than 0.02 mg/L (0.02 mcg/mL). Refer the patient to an obstetrician/gynecologist, preferably experienced in reproductive toxicity, for further evaluation and counseling.

Data

Animal Data

When teriflunomide (oral doses of 1, 3, or 10mg/kg/day) was administered …

8.2 Lactation

(PLLR conversion)

Risk Summary

It is not known whether this drug is excreted in human milk. Teriflunomide was detected in rat milk following a single oral dose.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AUBAGIO and any potential adverse effects on the breastfed infant from AUBAGIO or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Exclude pregnancy prior to initiation of treatment with AUBAGIO in females of reproductive potential. Advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment.

Contraception

Females

Females of reproductive potential should use effective contraception while taking AUBAGIO. If AUBAGIO is discontinued, use of contraception should be continued until is it verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL).

Females of reproductive potential who wish to become pregnant should 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).

Males

...To minimize any possible risk, men not wishing to father a child and their female partners should use effective contraception...

Infertility

Administration of teriflunomide to male rats resulted in no adverse effects on fertility. However, reduced epididymal sperm count was observed. Effects of AUBAGIO on fertility in humans have not been evaluated.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(additions and/or revisions are underlined)

Importance of Preventing Pregnancy

• Advise females of reproductive potential of the need for effective contraception during AUBAGIO treatment and until completion of an accelerated elimination procedure.

• Instruct men taking AUBAGIO 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 AUBAGIO and undergo an accelerated elimination procedure

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AUBAGIO during pregnancy.

 

Lactation

Inform patients that it is not known whether this drug is present in human milk. Advise patients, if they are considering breastfeeding, to discuss this with their healthcare provider to decide if they will take AUBAGIO or breastfeed. Advise patients that they should not do both.

06/02/2016 (SUPPL-3)

Approved Drug Label (PDF)

4 Contraindications

• (addition) Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO. Reactions have included anaphylaxis, angioedema, and serious skin reactions.

5 Warnings and Precautions

Bone Marrow Effects/Immunosuppression Potential/Infections

 Bone Marrow Effects (this heading replaces White Blood Cell (WBC) count decrease)

• Cases of thrombocytopenia with AUBAGIO, including rare cases with platelet counts less than 50,000/mm3, have been reported in the postmarketing setting. (addition of sentence to paragraph)

Hypersensitivity and Serious Skin Reactions

• AUBAGIO can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.
• Cases of serious skin reactions, including cases of Stevens-Johnson syndrome (SJS) and a fatal case of toxic epidermal necrolysis (TEN), have been reported with AUBAGIO.
• In patients treated with leflunomide, the parent compound, very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported.
• Inform patients of the signs and symptoms of anaphylaxis and angioedema and signs and symptoms that may signal a serious skin reaction. Inform patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, or hepatic dysfunction) may be drug-related. Instruct patients to discontinue AUBAGIO and seek immediate medical care should these signs and symptoms occur. Discontinue AUBAGIO, unless the reactions are clearly not drug-related, and begin an accelerated elimination procedure immediately. In such cases, patients should not be re-exposed to teriflunomide.

Respiratory Effects

• (addition of sentence) Interstitial lung disease, including acute interstitial pneumonitis, has been reported with AUBAGIO in the postmarketing setting.

6 Adverse Reactions

Hypersensitivity and Serious Skin Reactions (replaces Skin Reactions bullet)

 

Post-Marketing Experience (new subsection added)

The following adverse reactions have been identified during post approval use of AUBAGIO.

• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema
• Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome
• Thrombocytopenia
• Interstitial lung disease
• Pancreatitis

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MG - What are possible side effects of AUBAGIO?

AUBAGIO may cause serious side effects, including:

• Allergic reactions, including serious skin problems. Tell your doctor if you have difficulty breathing, itching, swelling on any part of your body including in your lips, eyes, throat or tongue, or any skin problems such as rash or redness and peeling. (update of prior bullet serious skin problems)

MG - Who should not take AUBAGIO?

Do not take AUBAGIO if you:

• you have had an allergic reaction to AUBAGIO or a medicine called leflunomide (addition)

PCI - Serious Allergic Reactions (new section added)

• Advise patients to discontinue AUBAGIO and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur. Signs and symptoms include dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue or skin rash.