AUBAGIO- teriflunomide tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TERIFLUNOMIDE (UNII: 1C058IKG3B) (TERIFLUNOMIDE - UNII:1C058IKG3B)

Available from:

Genzyme Corporation

INN (International Name):

teriflunomide

Composition:

teriflunomide 7 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

AUBAGIO® 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. AUBAGIO 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. AUBAGIO 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 AUBAGIO. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions (5.5)]. - Coadministration with leflunomide [see Clinical Pharmacology (12.3)]. 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 [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%–4% and 15%–20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. There is a pregnancy surveillance program for AUBAGIO. If AUBAGIO exposure occurs during pregnancy, healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2. 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 [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 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. 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. 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 [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 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 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 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) [see Warnings and Precautions (5.3)]. 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. Clinical studies of AUBAGIO did not include patients over 65 years old. No dosage adjustment is necessary for patients with mild and moderate hepatic impairment. The pharmacokinetics of teriflunomide in severe hepatic impairment has not been evaluated. AUBAGIO is contraindicated in patients with severe hepatic impairment [see Contraindications (4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)] . No dosage adjustment is necessary for patients with mild, moderate, and severe renal impairment [see Clinical Pharmacology (12.3)] .

Product summary:

AUBAGIO is available as 7 mg and 14 mg tablets. The 14 mg tablet is pale blue to pastel blue, pentagonal film-coated tablet with dose strength "14" imprinted on one side and engraved with corporate logo on the other side. Each tablet contains 14 mg of teriflunomide. The 7 mg tablet is very light greenish-bluish grey to pale greenish-blue, hexagonal film-coated tablet with dose strength "7" imprinted on one side and engraved with corporate logo on the other side. Each tablet contains 7 mg of teriflunomide. AUBAGIO 14 mg tablets are supplied as: AUBAGIO 7 mg tablets are supplied as: Store at 68°F to 77°F (20°C to 25°C) with excursions permitted between 59°F and 86°F (15°C and 30°C).

Authorization status:

New Drug Application

Patient Information leaflet

Genzyme Corporation
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This Medication Guide has been approved by the U.S. Food and
Drug Administration.
Revised: December 2023
Medication Guide
AUBAGIO® (oh-BAH-gee-oh)
(teriflunomide)
tablets, for oral use
Read this Medication Guide before you start using AUBAGIO 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 AUBAGIO?
AUBAGIO may cause serious side effects, including:
•
Liver problems: AUBAGIO 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 AUBAGIO
•
1 time a month for 6 months after you start taking AUBAGIO
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: AUBAGIO may cause harm to your unborn baby.
Do not take
AUBAGIO if you are pregnant. Do not take AUBAGIO unless you are using
effective birth
control.
•
If you are a female, you should have a pregnancy test before you start
taking AUBAGIO.
Use effective birth control during your treatment with AUBAGIO.
•
After stopping AUBAGIO, continue using effective birth control until
you have blood
tests to make sure your blood levels of AUBAGIO are low enough. If you
become
pregnant while taking AUBAGIO or within 2 years after you stop taking
it, tell your
doctor right away.
•
There is a pregnancy safety surveillance program for people who are
exposed to
AUBAGIO during pregnancy. The purpose of the program is to collect
information about

Summary of Product characteristics

AUBAGIO- TERIFLUNOMIDE TABLET, FILM COATED
GENZYME CORPORATION
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
AUBAGIO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR AUBAGIO.
AUBAGIO (TERIFLUNOMIDE) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2012
WARNING: HEPATOTOXICITY AND EMBRYOFETAL TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
HEPATOTOXICITY
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 (5.1). CONCOMITANT USE OF AUBAGIO WITH OTHER
HEPATOTOXIC
DRUGS MAY INCREASE THE RISK OF SEVERE LIVER INJURY. OBTAIN
TRANSAMINASE AND BILIRUBIN
LEVELS WITHIN 6 MONTHS BEFORE INITIATION OF AUBAGIO AND MONITOR ALT
LEVELS AT LEAST
MONTHLY FOR SIX MONTHS (5.1). IF DRUG INDUCED LIVER INJURY IS
SUSPECTED, DISCONTINUE
AUBAGIO AND START ACCELERATED ELIMINATION PROCEDURE (5.3).
EMBRYOFETAL TOXICITY
TERATOGENICITY AND EMBRYOLETHALITY OCCURRED IN ANIMALS ADMINISTERED
TERIFLUNOMIDE
(5.2, 8.1). EXCLUDE PREGNANCY PRIOR TO INITIATING AUBAGIO THERAPY (4,
5.2, 8.1, 8.3).
ADVISE USE OF EFFECTIVE CONTRACEPTION IN FEMALES OF REPRODUCTIVE
POTENTIAL DURING
TREATMENT AND DURING AN ACCELERATED DRUG ELIMINATION PROCEDURE (4,
5.2, 5.3, 8.1, 8.3).
STOP AUBAGIO AND USE AN ACCELERATED DRUG ELIMINATION PROCEDURE IF THE
PATIENT
BECOMES PREGNANT (5.2, 5.3, 8.1).
INDICATIONS AND USAGE
AUBAGIO is a pyrimidine synthesis inhibitor 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. (1)
DOSAGE AND ADMINISTRATION
7 mg or 14 mg orally once daily, with or without food. (2)
DOSAGE FORMS AND STRENGTHS
7 mg and 14 mg film-coated tablets (3)
CONTRAINDICATIONS
Severe hepatic impairment (4, 5.1)
Pregnancy (4, 5.2, 8.1)
Hypersensitivity (4, 5.5)
Current leflunomide treat