United States - English - NLM (National Library of Medicine)

genzyme corporation - teriflunomide (unii: 1c058ikg3b) (teriflunomide - unii:1c058ikg3b) - teriflunomide 7 mg - 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)] .

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - teriflunomide, quantity: 14 mg - tablet, film coated - excipient ingredients: magnesium stearate; sodium starch glycollate; microcrystalline cellulose; hyprolose; maize starch; lactose monohydrate; titanium dioxide; macrogol 8000; hypromellose; purified talc; indigo carmine aluminium lake - aubagio is indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical relapses and to delay the progression of physical disability.

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

zoetis australia pty ltd - contagious pustular dermatitis virus, living, cell cultu - misc. vaccines or anti sera - contagious pustular dermatitis virus, living, cell cultu vaccine-viral active 0.0 p - immunotherapy - lamb | sheep | ewe | hogget | lamb | ovine | ram | weaner | wether - scabby mouth | contagious ecthyma | contagious pustular dermatitis | cpd (scabby mouth) | orf (scabby mouth)

Ireland - English - HPRA (Health Products Regulatory Authority)

intervet ireland limited - contagious pustular dermatitis vaccine - suspension for skin scarification - per cent - orf virus vaccine / contagious pustular dermatitis vaccine - ovine - immunological - live vaccine

Ireland - English - HPRA (Health Products Regulatory Authority)

intervet ireland limited - contagious pustular dermatitis - cutaneous suspension - . - orf virus / contagious pustular dermatitis - sheep - immunological - live vaccine

Israel - English - Ministry of Health

sanofi israel ltd - teriflunomide - film coated tablets - teriflunomide 14 mg - teriflunomide - aubagio ® is indicated for the treatment of adult patients with relapsing remitting forms of multiple sclerosis (ms) ) to reduce the frequency of clinical relapses and to delay the progression of physical disability.

European Union - English - EMA (European Medicines Agency)

sanofi winthrop industrie - teriflunomide - multiple sclerosis - selective immunosuppressants - aubagio is indicated for the treatment of adult patients and paediatric patients aged 10 years and older with relapsing remitting multiple sclerosis (ms) (please refer to section 5.1 for important information on the population for which efficacy has been established).

New Zealand - English - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - teriflunomide 14mg;   - film coated tablet - 14 mg - active: teriflunomide 14mg   excipient: hyprolose lactose monohydrate magnesium stearate maize starch microcrystalline cellulose opadry blue 03f20651 sodium starch glycolate - aubagio is indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical relapses and to delay the progression of physical disability.

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

zoetis australia pty ltd - contagious pustular dermatitis virus, living, cell cultu - unknown - contagious pustular dermatitis virus, living, cell cultu vaccine-viral active 0.0 - active constituent

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - teriflunomide -