Evropská unie - nizozemština - EMA (European Medicines Agency)

ratiopharm gmbh - leflunomide - artritis, reumatoïde - immunosuppressiva - leflunomide is geïndiceerd voor de behandeling van volwassen patiënten met actieve reumatoïde artritis als een 'disease-modifying antirheumatic drug' (dmard);actieve artritis psoriatica. recente of gelijktijdige behandeling met hepatotoxische of haematotoxic dmard ' s (e. methotrexaat) kan leiden tot een verhoogd risico op ernstige bijwerkingen; daarom moet de start van de behandeling met leflunomide zorgvuldig worden overwogen met betrekking tot deze voordelen / risiceaspecten. bovendien, het overschakelen van leflunomide naar een ander dmard, zonder de wash-out procedure kan ook het risico van ernstige bijwerkingen, zelfs voor een lange tijd na het overschakelen.

Evropská unie - angličtina - EMA (European Medicines Agency)

teva pharma b.v. - leflunomide - arthritis, rheumatoid - immunosuppressants - leflunomide is indicated for the treatment of adult patients with active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (dmard).recent or concurrent treatment with hepatotoxic or haematotoxic dmards (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.moreover, switching from leflunomide to another dmard without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.

Spojené státy - angličtina - NLM (National Library of Medicine)

avkare - leflunomide (unii: g162gk9u4w) (leflunomide - unii:g162gk9u4w) - leflunomide tablets are indicated for the treatment of adults with active rheumatoid arthritis (ra). leflunomide is contraindicated in: - pregnant women. leflunomide may cause fetal harm. if a woman becomes pregnant while taking this drug, stop leflunomide, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see warnings and precautions ( 5.1 and 5.3) and use in specific populations ( 8.1)]. - patients with severe hepatic impairment [see warnings and precautions ( 5.2)]. - patients with known hypersensitivity to leflunomide or any of the other components of leflunomide. known reactions include anaphylaxis [see adverse reactions ( 6.1)]. - patients being treated with teriflunomide [see drug interactions ( 7)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to leflunomide during pregnancy. health care providers and patients are encouraged to report pregnancies by calling 1-877-311-8972 or visit http://www.pregnancystudies.org/participate-in­-a-study/. risk summary leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. in animal reproduction studies, oral administration of leflunomide during organogenesis at a dose of 1/10 of and equivalent to the maximum recommended human dose (mrhd) based on auc, respectively in rats and rabbits, caused teratogenicity (rats and rabbits) and embryo-lethality (rats) [see data] . pregnancy exposure registry data are not available at this time to inform the presence or absence of drug-associated risk with the use of leflunomide during pregnancy. the background risk of major birth defects and miscarriage for the indicated populations is unknown. the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, stop treatment with leflunomide, apprise the patient of the potential hazard to a fetus, and perform the accelerated drug elimination procedure to achieve teriflunomide concentrations of less than 0.02 mg/l (0.02 mcg/ml) [see warnings and precautions ( 5.3)]. clinical considerations fetal/neonatal adverse reactions lowering the plasma concentration of the active metabolite, teriflunomide, by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease the risk to the fetus from leflunomide. 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 animal data in an embryofetal development study, pregnant rats administered leflunomide during organogenesis from gestation days 7 to 19 at a dose approximately 1/10 of the mrhd (on an auc basis at a maternal oral dose of 15 mg/kg), teratogenic effects, most notably anophthalmia or microophthalmia and internal hydrocephalus, were observed. under these exposure conditions, leflunomide also caused a decrease in the maternal body weight and an increase in embryolethality with a decrease in fetal body weight for surviving fetuses. in an embryofetal development study, pregnant rabbits administered leflunomide during organogenesis from gestation days 6 to 18 at a dose approximately equivalent to the mrhd (on an auc basis at a maternal oral dose of 10 mg/kg), a teratogenic finding of fused, dysplastic sternebrae was observed. leflunomide was not teratogenic in rats and rabbits at doses approximately 1/150 and 1/10 of the mrhd, respectively (on an auc basis at maternal oral dose of 1 mg/kg in both rats and rabbits). in a pre- and post-natal development study, when female rats were treated leflunomide at a dose that was approximately 1/100 of the mrhd (on an auc basis at a maternal dose of 1.25 mg/kg) beginning 14 days before mating and continuing until the end of lactation, the offspring exhibited marked (greater than 90%) decreases in postnatal survival. risk summary clinical lactation studies have not been conducted to assess the presence of leflunomide in human milk, the effects of leflunomide on the breastfed child, or the effects of leflunomide on milk production. because of the potential for serious adverse reactions in a breastfed infant from leflunomide, advise a nursing woman to discontinue breastfeeding during treatment with leflunomide. leflunomide may cause fetal harm when administered during pregnancy. advise females of the potential risk to the fetus. advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment [see use in specific populations ( 8.1)] . women receiving leflunomide treatment who wish to become pregnant should discontinue leflunomide and undergo an accelerated drug elimination procedure to achieve plasma teriflunomide concentrations of less than 0.02 mg/l (0.02 mcg/ml) [see warnings and precautions ( 5.3)]. pregnancy testing exclude pregnancy in females of reproductive potential before starting treatment with leflunomide. contraception females advise females of reproductive potential to use effective contraception during treatment with leflunomide and while undergoing a drug elimination procedure until verification that the plasma teriflunomide concentration is less than 0.02 mg/l [see warnings and precautions ( 5.3)]. the safety and effectiveness of leflunomide in pediatric patients have not been established. the safety and effectiveness of leflunomide in the treatment of polyarticular course juvenile idiopathic arthritis (jia) was evaluated in a single multicenter, double-blind, active-controlled trial in 94 pediatric patients (1:1 randomization) with polyarticular course juvenile idiopathic arthritis (jia) as defined by the american college of rheumatology (acr). in this population, leflunomide treatment was found not to be effective. the safety of leflunomide was studied in 74 patients with polyarticular course jia ranging in age from 3 to 17 years (47 patients from the active-controlled study and 27 from an open-label safety and pharmacokinetic study). the most common adverse events included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness. less common adverse events included anemia, hypertension, and weight loss. fourteen pediatric patients experienced alt and/or ast elevations, nine between 1.2 and 3-fold the upper limit of normal, five between 3 and 8-fold the upper limit of normal. of the total number of subjects in controlled clinical trials (trials 1, 2, and 3) of leflunomide, 234 subjects were 65 years and over [see clinical studies ( 14)] . no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dosage adjustment is needed in patients over 65. dedicated studies of the effect of hepatic impairment on leflunomide pharmacokinetics have not been conducted. given the need to metabolize leflunomide into the active species, the role of the liver in drug elimination/recycling, and the possible risk of increased hepatic toxicity, the use of leflunomide in patients with hepatic impairment is not recommended. dedicated studies of the effect of renal impairment on leflunomide pharmacokinetics have not been conducted. given that the kidney plays an important role in drug elimination, caution should be used when leflunomide is administered to these patients.

Spojené státy - angličtina - NLM (National Library of Medicine)

avpak - leflunomide (unii: g162gk9u4w) (leflunomide - unii:g162gk9u4w) - leflunomide tablets are indicated for the treatment of adults with active rheumatoid arthritis (ra). leflunomide is contraindicated in: - pregnant women. leflunomide may cause fetal harm. if a woman becomes pregnant while taking this drug, stop leflunomide, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see warnings and precautions ( 5.1 and 5.3) and use in specific populations ( 8.1)]. - patients with severe hepatic impairment [see warnings and precautions ( 5.2)]. - patients with known hypersensitivity to leflunomide or any of the other components of leflunomide. known reactions include anaphylaxis [see adverse reactions ( 6.1)]. - patients being treated with teriflunomide [see drug interactions ( 7)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to leflunomide during pregnancy. health care providers and patients are encouraged to report pregnancies by calling 1-877-311-8972 or visit http://www.pregnancystudies.org/participate-in­-a-study/. risk summary leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. in animal reproduction studies, oral administration of leflunomide during organogenesis at a dose of 1/10 of and equivalent to the maximum recommended human dose (mrhd) based on auc, respectively in rats and rabbits, caused teratogenicity (rats and rabbits) and embryo-lethality (rats) [see data] . pregnancy exposure registry data are not available at this time to inform the presence or absence of drug-associated risk with the use of leflunomide during pregnancy. the background risk of major birth defects and miscarriage for the indicated populations is unknown. the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, stop treatment with leflunomide, apprise the patient of the potential hazard to a fetus, and perform the accelerated drug elimination procedure to achieve teriflunomide concentrations of less than 0.02 mg/l (0.02 mcg/ml) [see warnings and precautions ( 5.3)]. clinical considerations fetal/neonatal adverse reactions lowering the plasma concentration of the active metabolite, teriflunomide, by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease the risk to the fetus from leflunomide. 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 animal data in an embryofetal development study, pregnant rats administered leflunomide during organogenesis from gestation days 7 to 19 at a dose approximately 1/10 of the mrhd (on an auc basis at a maternal oral dose of 15 mg/kg), teratogenic effects, most notably anophthalmia or microophthalmia and internal hydrocephalus, were observed. under these exposure conditions, leflunomide also caused a decrease in the maternal body weight and an increase in embryolethality with a decrease in fetal body weight for surviving fetuses. in an embryofetal development study, pregnant rabbits administered leflunomide during organogenesis from gestation days 6 to 18 at a dose approximately equivalent to the mrhd (on an auc basis at a maternal oral dose of 10 mg/kg), a teratogenic finding of fused, dysplastic sternebrae was observed. leflunomide was not teratogenic in rats and rabbits at doses approximately 1/150 and 1/10 of the mrhd, respectively (on an auc basis at maternal oral dose of 1 mg/kg in both rats and rabbits). in a pre- and post-natal development study, when female rats were treated leflunomide at a dose that was approximately 1/100 of the mrhd (on an auc basis at a maternal dose of 1.25 mg/kg) beginning 14 days before mating and continuing until the end of lactation, the offspring exhibited marked (greater than 90%) decreases in postnatal survival. risk summary clinical lactation studies have not been conducted to assess the presence of leflunomide in human milk, the effects of leflunomide on the breastfed child, or the effects of leflunomide on milk production. because of the potential for serious adverse reactions in a breastfed infant from leflunomide, advise a nursing woman to discontinue breastfeeding during treatment with leflunomide. leflunomide may cause fetal harm when administered during pregnancy. advise females of the potential risk to the fetus. advise females to notify their healthcare provider immediately if pregnancy occurs or is suspected during treatment [see use in specific populations ( 8.1)] . women receiving leflunomide treatment who wish to become pregnant should discontinue leflunomide and undergo an accelerated drug elimination procedure to achieve plasma teriflunomide concentrations of less than 0.02 mg/l (0.02 mcg/ml) [see warnings and precautions ( 5.3)]. pregnancy testing exclude pregnancy in females of reproductive potential before starting treatment with leflunomide. contraception females advise females of reproductive potential to use effective contraception during treatment with leflunomide and while undergoing a drug elimination procedure until verification that the plasma teriflunomide concentration is less than 0.02 mg/l [see warnings and precautions ( 5.3)]. the safety and effectiveness of leflunomide in pediatric patients have not been established. the safety and effectiveness of leflunomide in the treatment of polyarticular course juvenile idiopathic arthritis (jia) was evaluated in a single multicenter, double-blind, active-controlled trial in 94 pediatric patients (1:1 randomization) with polyarticular course juvenile idiopathic arthritis (jia) as defined by the american college of rheumatology (acr). in this population, leflunomide treatment was found not to be effective. the safety of leflunomide was studied in 74 patients with polyarticular course jia ranging in age from 3 to 17 years (47 patients from the active-controlled study and 27 from an open-label safety and pharmacokinetic study). the most common adverse events included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness. less common adverse events included anemia, hypertension, and weight loss. fourteen pediatric patients experienced alt and/or ast elevations, nine between 1.2 and 3-fold the upper limit of normal, five between 3 and 8-fold the upper limit of normal. of the total number of subjects in controlled clinical trials (trials 1, 2, and 3) of leflunomide, 234 subjects were 65 years and over [see clinical studies ( 14)] . no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dosage adjustment is needed in patients over 65. dedicated studies of the effect of hepatic impairment on leflunomide pharmacokinetics have not been conducted. given the need to metabolize leflunomide into the active species, the role of the liver in drug elimination/recycling, and the possible risk of increased hepatic toxicity, the use of leflunomide in patients with hepatic impairment is not recommended. dedicated studies of the effect of renal impairment on leflunomide pharmacokinetics have not been conducted. given that the kidney plays an important role in drug elimination, caution should be used when leflunomide is administered to these patients.

Evropská unie - italština - EMA (European Medicines Agency)

teva pharma b.v. - leflunomide - artrite, reumatoide - immunosoppressori - leflunomide è indicato per il trattamento di pazienti adulti con artrite reumatoide attiva come "farmaco antireumatico modificante la malattia" (dmard). recenti o in trattamento concomitante con epatotossici o haematotoxic dmards (e. metotrexato) può comportare un aumento del rischio di reazioni avverse gravi; pertanto, l'inizio del trattamento con leflunomide deve essere attentamente considerato per quanto riguarda questi aspetti benefici / rischi. inoltre, il passaggio da leflunomide ad un altro dmard, senza seguire la procedura di washout può anche aumentare il rischio di gravi reazioni avverse, anche per lungo tempo dopo la commutazione.

Evropská unie - italština - EMA (European Medicines Agency)

medac gesellschaft für klinische spezialpräparate mbh - leflunomide - artrite, reumatoide - immunosoppressori selettivi - leflunomide è indicato per il trattamento di pazienti adulti con:artrite reumatoide attiva, come una 'malattia farmaci antireumatici modificanti la' (dmard). recenti o in trattamento concomitante con epatotossici o haematotoxic dmards (e. methotrexate) può causare un aumento del rischio di gravi reazioni avverse, pertanto, l'avvio di leflunomide trattamento deve essere attentamente considerato per quanto riguarda queste beneficio / rischio aspetti. inoltre, il passaggio da leflunomide ad un altro dmard, senza seguire la procedura di washout può anche aumentare il rischio di gravi reazioni avverse, anche per lungo tempo dopo la commutazione.

Evropská unie - italština - EMA (European Medicines Agency)

ratiopharm gmbh - leflunomide - artrite, reumatoide - immunosoppressori - leflunomide è indicato per il trattamento di pazienti adulti con:artrite reumatoide attiva, come una 'malattia farmaci antireumatici modificanti la' (dmard);artrite psoriasica attiva. recenti o in trattamento concomitante con epatotossici o haematotoxic dmards (e. metotrexato) può comportare un aumento del rischio di reazioni avverse gravi; pertanto, l'inizio del trattamento con leflunomide deve essere attentamente considerato per quanto riguarda questi aspetti benefici / rischi. inoltre, il passaggio da leflunomide ad un altro dmard, senza seguire la procedura di washout può anche aumentare il rischio di gravi reazioni avverse, anche per lungo tempo dopo la commutazione.

Evropská unie - angličtina - EMA (European Medicines Agency)

medac gesellschaft für klinische spezialpräparate mbh - leflunomide - arthritis, rheumatoid - selective immunosuppressants - leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (dmard).recent or concurrent treatment with hepatotoxic or haematotoxic dmards (e.g. methotrexate) may result in an increased risk of serious adverse reactions, therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.moreover, switching from leflunomide to another dmard without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.

Evropská unie - angličtina - EMA (European Medicines Agency)

ratiopharm gmbh - leflunomide - arthritis, rheumatoid - immunosuppressants - leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (dmard);active psoriatic arthritis.recent or concurrent treatment with hepatotoxic or haematotoxic dmards (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.moreover, switching from leflunomide to another dmard without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.

Evropská unie - finština - EMA (European Medicines Agency)

zentiva k.s. - leflunomidi - arthritis, rheumatoid; arthritis, psoriatic - immunosuppressantit - leflunomidi on tarkoitettu aikuisille potilaille, joilla on:aktiivisen nivelreuman hoitoon, kuten sairauden kulkuun pitkällä aikavälillä vaikuttavana reumalääkkeenä' (dmard);aktiivinen nivelpsoriaasi. Äskettäinen tai samanaikainen hoito maksa-tai haematotoxic reumalääkkeet (e. metotreksaatti) voi johtaa kohonnut vakavista haittavaikutuksista; leflunomide hoidon aloittamista onkin tarkasteltava huolellisesti osalta nämä hyöty / riski näkökohtia. lisäksi leflunomidin vaihto toiseen dmard ilman elimistöstä poistamismenetelmän käyttöä voi myös lisätä riskiä vakavia haittavaikutuksia, jopa pitkän ajan jälkeen kytkentä.