TERIFLUNOMIDE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Aurobindo Pharma Limited

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Teriflunomide tablets are 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. Teriflunomide tablets are 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)].   - Coadministration with leflunomide [see Clinical Pharmacology (12.3)]. Risk Summary Teriflunomide 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. 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 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 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 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 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. Pregnancy Testing Exclude pregnancy prior to initiation of treatment with teriflunomide 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. If teriflunomide 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 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 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. 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 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. Teriflunomide 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:

Teriflunomide is available as 7 mg and 14 mg tablets. 7 mg tablet is light green to green, round shaped film-coated tablet debossed with “N” on one side and with “7” on the other side. Each tablet contains 7 mg teriflunomide. Cartons of 28 tablets containing 2 blisters of 14 tablets each      NDC 59651-054-28 Bottles of 30                                                                                NDC 59651-054-30 14 mg tablet is light blue to blue, round shaped film-coated tablet debossed with “N” on one side and with “14” on the other side. Each tablet contains 14 mg teriflunomide. Cartons of 28 tablets containing 2 blisters of 14 tablets each     NDC 59651-055-28 Bottles of 30                                                                                NDC 59651-055-30 Store at 20o to 25o C (68o to 77o F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Aurobindo Pharma Limited
----------
Medication Guide
Teriflunomide Tablets
(ter-i-FLOO-noh-mide), for oral use
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.
•
For men taking teriflunomide tablets:
•
If your female partner plans to become

Summary of Product characteristics

TERIFLUNOMIDE - TERIFLUNOMIDE TABLET
AUROBINDO PHARMA LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TERIFLUNOMIDE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
TERIFLUNOMIDE TABLETS.
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 TERIFLUNOMIDE
TABLETS IN THE POSTMARKETING SETTING (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 AND
MONITOR ALT LEVELS AT LEAST MONTHLY FOR SIX MONTHS (5.1). IF DRUG
INDUCED LIVER INJURY IS
SUSPECTED, DISCONTINUE TERIFLUNOMIDE 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 TERIFLUNOMIDE
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 TERIFLUNOMIDE AND USE AN ACCELERATED DRUG ELIMINATION PROCEDURE
IF THE PATIENT
BECOMES PREGNANT (5.2, 5.3, 8.1).
INDICATIONS AND USAGE
Teriflunomide tablets are 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 imp