Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

medsource pharmaceuticals - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder [see clinical studies (14.1)] - generalized anxiety disorder [see clinical studies (14.2)] - diabetic peripheral neuropathy [see clinical studies (14.3)] - chronic musculoskeletal pain [see clinical studies (14.5)] monoamine oxidase inhibitors (maois) — the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)]. starting d

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder [see clinical studies (14.1)] - generalized anxiety disorder [see clinical studies (14.2)] - diabetic peripheral neuropathy [see clinical studies (14.3)] - chronic musculoskeletal pain [see clinical studies (14.5)] monoamine oxidase inhibitors (maois) — the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)]. starting duloxetine delayed-release capsules in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of seroton

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

quality care products, llc - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder [see clinical studies ( 14.1 )] . - generalized anxiety disorder [see clinical studies ( 14.2 )] . - diabetic peripheral neuropathy [see clinical studies ( 14.3 )] . - chronic musculoskeletal pain [see clinical studies ( 14.5 )] .          monoamine oxidase inhibitors (maois) - the use of maois intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)].          starting duloxetine in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9) and warnings and

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

eli lilly and company - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - cymbalta® is indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with cymbalta or within 5 days of stopping treatment with cymbalta is contraindicated because of an increased risk of serotonin syndrome. the use of cymbalta within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)] . starting cymbalta in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9) and warnings and precautions (5.4)] . pregnancy exposure registry there

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

alembic pharmaceuticals limited - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsule or within 5 days of stopping treatment with duloxetine delayed-release capsule is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)]. starting duloxetine delayed-release capsule in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9)

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder [see clinical studies ( 14.1 )] . - generalized anxiety disorder [see clinical studies ( 14.2 )] . - diabetic peripheral neuropathy [see clinical studies ( 14.3 )] . - chronic musculoskeletal pain [see clinical studies ( 14.5 )] .          monoamine oxidase inhibitors (maois)   - the use of maois intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)].          starting duloxetine in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9) and warnings an

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

golden state medical supply, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules is indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8)and warnings and precautions (5.4)]. starting duloxetine delayed-release capsules in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9)and warnings and precautions (5.4)]. risk summary data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see data) . there are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to snris and ssris, including duloxetine delayed-release capsules, during pregnancy (see clinical considerations). in rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (mrhd) of 120 mg/day given to adolescents on a mg/m 2 basis. when duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the mrhd given to adolescents on a mg/m 2 basis. at this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. post-weaning growth was not adversely affected. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. 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. clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. it is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. maternal adverse reactions use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)]. fetal/neonatal adverse reaction neonates exposed to duloxetine delayed-release capsules and other snris or ssris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of the snris or ssris, or possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.4)]. data human data data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% ci: 1.08-2.18). the same study did not find a clinically meaningful increase in the risk for major birth defects in the comparison of 2532 women exposed to duloxetine in the first trimester of pregnancy to 1,284,827 unexposed women after adjusting for several confounders. methodologic limitations include possible residual confounding, misclassification of exposure and outcomes, lack of direct measures of disease severity, and lack of information about alcohol use, nutrition, and over-the-counter medication exposures. animal data in animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. when duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of malformations or developmental variations at doses up to 45 mg/kg/day [3 and 6 times, respectively, the mrhd of 120 mg/day given to adolescents on a mg/m 2 basis]. however, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the mrhd in rats and 2 times the mrhd in rabbits). when duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the mrhd given to adolescents on a mg/m 2 basis); the no-effect dose was 10 mg/kg/day. furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. risk summary data from published literature report the presence of duloxetine in human milk (see data) . there are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk (see clinical considerations). there are no data on the effect of duloxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for duloxetine delayed-release capsules and any potential adverse effects on the breastfed child from duloxetine delayed-release capsules or from the underlying maternal condition. clinical considerations infants exposed to duloxetine delayed-release capsules should be monitored for sedation, poor feeding and poor weight gain. data disposition of duloxetine delayed-release capsules was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. the women were given 40 mg of duloxetine delayed-release capsules twice daily for 3.5 days. the peak concentration measured in breast milk occurred at a median of 3 hours after the dose. the amount of duloxetine in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day, which is less than 1% of the maternal dose. the presence of duloxetine metabolites in breast milk was not examined. the safety and effectiveness of duloxetine delayed-release capsules have been established for treatment of generalized anxiety disorder (gad) in patients 7 to 17 years of age and for treatment of juvenile fibromyalgia syndrome in patients 13 to 17 years of age. the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients with major depressive disorder (mdd), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. monitor all pediatric patients being treated with antidepressants for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment, or at times of dosage changes [see warnings and precautions (5.1)] . perform regular monitoring of weight and growth in pediatric patients treated with duloxetine delayed-release capsules [see adverse reactions (6.1)]. generalized anxiety disorder use of duloxetine delayed-release capsules for the treatment of gad in patients 7 to 17 years of age is supported by one 10-week, placebo- controlled trial (gad-6). the study included 272 pediatric patients with gad of which 47% were 7 to 11 years of age (53% were 12 to 17 years of age). duloxetine delayed-release capsules demonstrated superiority over placebo as measured by greater improvement in the pediatric anxiety rating scale (pars) for gad severity score [see clinical studies (14.3)]. the safety and effectiveness of duloxetine delayed-release capsules for the treatment of gad in pediatric patients less than 7 years of age have not been established. fibromyalgia use of duloxetine delayed-release capsules for treatment of fibromyalgia in patients 13 to 17 years of age is supported by a 13-week placebo- controlled trial in 184 patients with juvenile fibromyalgia syndrome (study fm-4). duloxetine delayed-release capsules showed improvement over placebo on the primary endpoint, change from baseline to end-of-treatment on the brief pain inventory (bpi) – modified short form: adolescent version 24-hour average pain severity rating [see clinical studies (14.5)] . the safety and effectiveness of duloxetine delayed-release capsules for the treatment of fibromyalgia in patients less than 13 years of age have not been established. major depressive disorder the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients for the treatment of mdd. efficacy of duloxetine delayed-release capsules was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients aged 7 to 17 years old with mdd (mdd-6 and mdd-7). neither duloxetine delayed-release capsules nor an active control (approved for treatment of pediatric mdd) was superior to placebo. the most frequently observed adverse reactions in the mdd pediatric clinical trials included nausea, headache, decreased weight, and abdominal pain. decreased appetite and weight loss have been observed in association with the use of ssris and snris. juvenile animal toxicology data duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. these effects were observed at the high dose of 45 mg/kg/day (2 times the mrhd, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the mrhd, for a child). geriatric exposure in premarketing clinical trials of duloxetine delayed-release capsules - of the 2,418 patients in mdd trials, 6% (143) were 65 years of age or over. - of the 1,041 patients in clbp trials, 21% (221) were 65 years of age or over. - of the 487 patients in oa trials, 41% (197) were 65 years of age or over. - of the 1,074 patients in the dpnp trials, 33% (357) were 65 years of age or over. - of the 1,761 patients in fm trials, 8% (140) were 65 years of age or over. in the mdd, gad, dpnp, fm, oa, and clbp studies, no overall differences in safety or effectiveness were generally observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between these geriatric and younger adult patients, but greater sensitivity of some older patients cannot be ruled out. ssris and snris, including duloxetine delayed-release capsules have been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.13)]. in an analysis of data from all placebo-controlled-trials, duloxetine delayed-release capsules-treated patients reported a higher rate of falls compared to placebo-treated patients. the increased risk appears to be proportional to a patient's underlying risk for falls. underlying risk appears to increase steadily with age. as geriatric patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during duloxetine delayed-release capsules treatment is unclear. falls with serious consequences including bone fractures and hospitalizations have been reported with duloxetine delayed-release capsules use [see warnings and precautions (5.3)and adverse reactions (6.1)]. the pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). there was no difference in the c max , but the auc of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. dosage adjustment based on the age of the adult patient is not necessary. duloxetine's half-life is similar in men and women. dosage adjustment based on gender is not necessary. duloxetine bioavailability (auc) appears to be reduced by about one-third in smokers. dosage modifications are not recommended for smokers. no specific pharmacokinetic study was conducted to investigate the effects of race. patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. after a single 20 mg dose of duloxetine delayed-release capsules, 6 cirrhotic patients with moderate liver impairment (child-pugh class b) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (auc). although c max was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see dosage and administration (2.7)and warnings and precautions (5.14)]. limited data are available on the effects of duloxetine in patients with end-stage renal disease (esrd). after a single 60 mg dose of duloxetine, c max and auc values were approximately 100% greater in patients with esrd receiving chronic intermittent hemodialysis than in subjects with normal renal function. the elimination half-life, however, was similar in both groups. the aucs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6- methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. population pk analyses suggest that mild to moderate degrees of renal impairment (estimated crcl 30-80 ml/min) have no significant effect on duloxetine apparent clearance [see dosage and administration (2.7)and warnings and precautions (5.14)]. in animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. while duloxetine delayed-release capsules have not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine delayed-release capsules (e.g., development of tolerance, incrementation of dose, drug-seeking behavior). in drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

arcutis biotherapeutics, inc. - roflumilast (unii: 0p6c6zop5u) (roflumilast - unii:0p6c6zop5u) - zoryve® cream is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. zoryve cream is contraindicated in patients with moderate to severe liver impairment (child-pugh b or c) [see use in specific populations (8.6), clinical pharmacology (12.3)] . risk summary there are insufficient data available on the use of zoryve cream in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. in animal reproduction studies, roflumilast administered orally to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 36 and 31 times the maximum recommended human dose (mrhd), respectively. roflumilast induced post-implantation loss in rats at oral doses greater than or equal to 12 times the mrhd. roflumilast induced stillbirth and decreased pup viability in mice at oral doses 19 and 59 times the mrhd, respectively. roflumilast has been shown to adversely affect pup post-natal development when dams were treated with an oral dose 59 times the mrhd during pregnancy and lactation periods in mice (see data) . the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. 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. clinical considerations labor and delivery avoid using zoryve cream during labor and delivery. there are no human studies that have investigated effects of zoryve cream on preterm labor or labor at term; however, animal studies showed that oral roflumilast disrupted the labor and delivery process in mice. data animal data in an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast (36 times the mrhd on a mg/m2 basis). no evidence of structural abnormalities or effects on survival rates were observed. roflumilast did not affect embryo-fetal development at a maternal oral dose of 0.2 mg/kg/day (4 times the mrhd on a mg/m2 basis). in a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast for 10 weeks and females for 2 weeks prior to pairing and throughout the organogenesis period. roflumilast induced pre- and post-implantation loss at maternal oral doses greater than or equal to 0.6 mg/kg/day (12 times the mrhd on a mg/m2 basis). roflumilast did not cause fetal structural abnormalities at maternal oral doses up to 1.8 mg/kg/day (35 times the mrhd on a mg/m2 basis). in an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast during the period of organogenesis. roflumilast did not cause fetal structural abnormalities at the maternal oral doses of 0.8 mg/kg/day (31 times the mrhd on a mg/m2 basis). in pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast during the period of organogenesis and lactation. roflumilast induced stillbirth and decreased pup viability at maternal oral doses greater than 2 mg/kg/day and 6 mg/kg/day, respectively (19 and 59 times the mrhd on a mg/m2 basis, respectively). roflumilast induced delivery retardation in pregnant mice at maternal oral doses greater than 2 mg/kg/day (19 times the mrhd on a mg/m2 basis). roflumilast decreased pup rearing frequencies at a maternal oral dose of 6 mg/kg/day during pregnancy and lactation (59 times the mrhd on a mg/m2 basis). roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at a maternal oral dose of 12 mg/kg/day (116 times the mrhd on a mg/m2 basis). risk summary there are no data on the presence of roflumilast or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. roflumilast and/or its metabolites are excreted into the milk of lactating rats (see data) . when a drug is present in animal milk, it is likely that the drug will present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for zoryve cream and any potential adverse effects on the breastfed infant from zoryve cream or from the underlying maternal condition. clinical considerations to minimize potential exposure to the breastfed infant via breast milk, use zoryve cream on the smallest area of skin and for the shortest duration possible while breastfeeding. to avoid direct infant exposure, advise breastfeeding women not to apply zoryve cream directly to the nipple or areola. if applied to the patient's chest, avoid exposure via direct contact with the infant's skin. data animal data roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively. the safety and effectiveness of zoryve cream for the treatment of plaque psoriasis have been established in pediatric patients 6 years of age and older. use of zoryve cream in pediatric patients 6 to less than 18 years of age is supported by data from two 8-week, vehicle-controlled safety and efficacy trials which included 18 pediatric subjects 6 to 17 years of age, of whom 11 received zoryve cream. use of zoryve cream in pediatric patients 12 to 17 years of age is also supported by data from open-label trials of 2 and 24 weeks duration which included 18 pediatric subjects 12 to 17 years of age treated with zoryve cream. use of zoryve cream in pediatric patients 6 to less than 12 years of age is also supported by data from one 4-week, open-label, safety and pharmacokinetic (pk) study which included 20 pediatric subjects 6 to less than 12 years of age. the adverse reaction profile in subjects 6 to less than 18 years of age was consistent with that observed in adults [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14)] . the safety and effectiveness of zoryve cream in pediatric patients below the age of 6 years have not been established. of the 881 subjects with psoriasis exposed to zoryve cream or vehicle for up to 8 weeks in 2 controlled clinical trials, 106 were 65 years of age or older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out. based on available data for roflumilast, no adjustment of dosage in geriatric patients is warranted [see clinical pharmacology (12.3)] . oral roflumilast 250 mcg once daily for 14 days was studied in subjects with hepatic impairment. the systemic exposure of roflumilast and roflumilast n-oxide were increased in subjects with moderate (child-pugh b) hepatic impairment. zoryve cream is contraindicated in patients with moderate to severe liver impairment (child-pugh b or c). no dosage adjustment is needed in patients with mild (child-pugh a) hepatic impairment [see contraindications (4), clinical pharmacology (12.3)] .

Канада - Енглески - Health Canada

ferrer internacional, s.a. - ozenoxacin - cream - 1% - ozenoxacin 1% - antibiotics

Нови Зеланд - Енглески - Ministry for Primary Industries

fmc new zealand limited - fenoxaprop-p ethyl - fenoxaprop-p ethyl 69 g/litre - herbicide