Stati Uniti - Ingliż - NLM (National Library of Medicine)

nucare pharmaceuticals, inc. - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9) - omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. most patients heal within four weeks. some patients may require an additional four weeks of therapy. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate h. pylori in adults. dual therapy omeprazole delayed-release capsules in combination with clarithromycin are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease to eradicate h. pylori in adults. among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. in patients who fail therapy, susceptibil

Stati Uniti - Ingliż - NLM (National Library of Medicine)

preferred pharmaceuticals, inc. - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9) - omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. most patients heal within four weeks. some patients may require an additional four weeks of therapy. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate h. pylori in adults. dual therapy omeprazole delayed-release capsules in combination with clarithromycin are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease to eradicate h. pylori in adults. among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. in patients who fail therapy, susceptibil

Stati Uniti - Ingliż - NLM (National Library of Medicine)

remedyrepack inc. - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9) - omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. most patients heal within four weeks. some patients may require an additional four weeks of therapy. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate h. pylori in adults. dual therapy omeprazole delayed-release capsules in combination with clarithromycin are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease to eradicate h. pylori in adults. among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance

Stati Uniti - Ingliż - NLM (National Library of Medicine)

mylan pharmaceuticals inc. - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole 15 mg - lansoprazole delayed-release capsules are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies (14.1)] . lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy are indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate h. pylori . eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)] . please refer to the full prescribing information for amoxicillin and clarithromycin. lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy are indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)] . please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months [see clinical studies (14.3)] . lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies (14.4)] . lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies (14.5)] . lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies (14.6)] . lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies (14.7)] . lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole delayed-release capsules for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole delayed-release capsules may be considered [see clinical studies (14.8)] . lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies (14.9)] . lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies (14.10)] . available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data) . in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data) . these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are 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. if lansoprazole delayed-release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr) = 1.04, [95% confidence interval (ci) 0.25-4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or) = 1.12, [95% ci 0.86-1.45] and for spontaneous abortions or = 1.29, [95% ci 0.84-1.97]). no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed-release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed-release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules have been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole was not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data) . lansoprazole was not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo-controlled study. therefore, safety and effectiveness have not been established in patients less than one year of age. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04- and 1.88-fold higher at doses of 0.5 and 1 mg/kg/day, respectively). infants aged ≤ 10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week, multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., nonpharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤ 10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. in an uncontrolled, open-label, u.s. multicenter study, 66 pediatric patients (one year to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole 15 mg daily if ≤ 30 kg or lansoprazole 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline, 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty-one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4) . gerd final visit * % (n/n) symptomatic gerd     improvement in overall gerd symptoms† 76% (47/62‡) erosive esophagitis     improvement in overall gerd symptoms† 81% (22/27)     healing rate 100% (27/27) in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ml at baseline to 97 pg/ml [interquartile range (25th to 75th percentile) of 71 to 130 pg/ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd, 85% (56/66) took lansoprazole for eight weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n = 66) were constipation (5%) and headache (3%). in an uncontrolled, open-label, u.s. multicenter study, 87 adolescent patients (12 years to 17 years of age) with symptomatic gerd were treated with lansoprazole for eight to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) non-erosive gerd and 23 (26%) erosive esophagitis (ee). the non-erosive gerd patients received lansoprazole 15 mg daily for eight weeks and the ee patients received lansoprazole 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during eight weeks of lansoprazole treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole treatment. one patient remained unhealed after 12 weeks of treatment (table 5) . gerd final visit % (n/n) symptomatic gerd (all patients)     improvement in overall gerd symptoms* 73.2% (60/82)† non-erosive gerd     improvement in overall gerd symptoms* 71.2% (42/59)† erosive esophagitis     improvement in overall gerd symptoms* 78.3% (18/23)     healing rate‡ 95.5% (21/22)‡ in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25th to 75th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml.) the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with non-erosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n = 21,486) in clinical studies of lansoprazole, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology (12.3)] . no dosage adjustment for lansoprazole delayed-release capsules is necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [see dosage and administration (2.3)] . lansoprazole delayed-release capsules usp, for oral use (lan soe′ pra zole) important: lansoprazole delayed-release capsules: taking lansoprazole delayed-release capsules with certain foods: you can only use applesauce, ensure pudding, cottage cheese, yogurt or strained pears. taking lansoprazole delayed-release capsules with certain juices: you can only use apple juice, orange juice or tomato juice. giving lansoprazole delayed-release capsules through a nasogastric tube (ng tube) size 16 french or larger: you can only use apple juice. how should i store lansoprazole delayed-release capsules? keep lansoprazole delayed-release capsules and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. the brand names listed are trademarks of their respective owners. manufactured for: mylan pharmaceuticals inc. morgantown, wv 26505 u.s.a. manufactured by: mylan laboratories limited hyderabad — 500 096, india 75102577 revised: 3/2024 mx:lans:r13mmh/mx:mg:lans:r6m/mx:mg:lans:r6mh

Stati Uniti - Ingliż - NLM (National Library of Medicine)

mckesson corporation dba sky packaging - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole 30 mg - lansoprazole delayed-release capsules are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies ( 14.1) ].    triple therapy: lansoprazole delayed-release capsules/amoxicillin/clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate h. pylori. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies ( 14.2) ]. please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole delayed-release capsules /amoxicillin lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies ( 14.2) ]. please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months. [see clinical studies ( 14.3) ]. lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies ( 14.4) ]. lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies ( 14.5) ].   lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies ( 14.6) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies ( 14.7) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole delayed-release capsules for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole delayed-release capsules may be considered [see clinical studies ( 14.8)]. lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies ( 14.9) ]. lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies ( 14.10) ]. - lansoprazole delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6) ]. - proton pump inhibitors (ppis), including lansoprazole delayed-release capsules are contraindicated with rilpivirine-containing products [see drug interactions ( 7 )]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole delayed-release capsules, refer to the contraindications section of their prescribing information. risk summary available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data). in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data). these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are 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. if lansoprazole delayed-release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=1.04, [95% confidence interval (ci) 0.25 to 4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or)=1.12, [95% ci 0.86 to 1.45] and for spontaneous abortions or=1.29, [95% ci 0.84 to 1.97]). animal data no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed-release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed-release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules have been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole was not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data). lansoprazole was not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo controlled study. therefore, safety and effectiveness have not been established in patients less than one year. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. neonate to less than one year of age the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04 and 1.88 fold higher at doses of 0.5 mg/kg/day and 1 mg/kg/day, respectively). infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week multi-center, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., non-pharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. one year to 11 years of age in an uncontrolled, open-label, u.s. multi-center study, 66 pediatric patients (one year to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole delayed-release capsules 15 mg daily if ≤ 30 kg or lansoprazole delayed-release capsules 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline, 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4). final visit * % (n/n) * at week 8 or week 12 † symptoms assessed by patients diary kept by caregiver. ‡ no data were available for four pediatric patients. in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole delayed-release capsules given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ ml at baseline to 97 pg/ml [interquartile range (25 th to 75 th percentile) of 71 to 130 pg/ ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd 85% (56/66) took lansoprazole delayed-release capsules for eight weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n=66) were constipation (5%) and headache (3%). twelve years to 17 years of age in an uncontrolled, open-label, u.s. multi-center study, 87 adolescent patients (12 years to 17 years of age) with symptomatic gerd were treated with lansoprazole delayed-release capsules for eight to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) non-erosive gerd and 23 (26%) erosive esophagitis (ee). the non-erosive gerd patients received lansoprazole delayed-release capsules 15 mg daily for eight weeks and the ee patients received lansoprazole delayed-release capsules 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during eight weeks of lansoprazole delayed-release capsules treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole delayed-release capsules treatment. one patient remained unhealed after 12 weeks of treatment (table 5). *symptoms assessed by patient diary (parents/caregivers as necessary). † no data available for five patients. ‡ data from one healed patient was excluded from this analysis due to timing of final endoscopy. in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25 th to 75 th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml). the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole delayed-release capsules for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with non-erosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. bone changes in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=21,486) in clinical studies of lansoprazole delayed-release capusles, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology ( 12.3) ]. in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology ( 12.3) ]. no dosage adjustment for lansoprazole delayed-release capsules are necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [ see dosage and administration ( 2.3)] .

Stati Uniti - Ingliż - NLM (National Library of Medicine)

lupin pharmaceuticals, inc. - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq), esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole magnesium, are indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. the naproxen component of naproxen and esomeprazole magnesium delayed-release tablets is indicated for relief of signs and symptoms of: -   osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. -   juvenile idiopathic arthritis (jia) in adolescent patients. the esomeprazole magnesium component of naproxen and esomeprazole magnesium delayed-release tablets is indicated to decrease the risk of developing naproxen-associated gastric ulcers. limitations   of use: -   do not substitute naproxen and esomeprazole magnesium delayed-release tablet with the single-ingredient products of naproxen and esomeprazole magnesium. -   naproxen and esomeprazole magnesium delayed-release tablet is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. -   controlled studies do not extend beyond 6 months [see use in specific populations (8.4), clinical studies (14)] . naproxen and esomeprazole magnesium delayed-release tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.7, 5.8, 5.9,5.18), adverse reactions (6.2)] . - history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] . - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1)] . - proton pump inhibitors (ppis), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus and fetal and renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of naproxen and esomeprazole magnesium delayed-release tablets use between about 20 and 30 weeks of gestation and avoid naproxen and esomeprazole magnesium delayed-release tablets use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data) . premature closure of the fetal ductus arteriosus use of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. naproxen and esomeprazole magnesium delayed-release tablet contains naproxen and esomeprazole magnesium. esomeprazole is the s- isomer of omeprazole. naproxen data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, naproxen administered during organogenesis to rats and rabbits at doses less than the maximum recommended human daily dose of 1500 mg/day showed no evidence of harm to the fetus (see data) . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. esomeprazole there are no human data for esomeprazole. however, available epidemiologic data for omeprazole (esomeprazole is the s-isomer of omeprazole) fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see data) . in animal studies with administration of oral esomeprazole magnesium in rats changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see data] . the estimated background risks of major birth defects and miscarriage for the indicated population are 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 fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, can cause premature closure of the fetal ductus arteriosus (see data). oligohydramnios/neonatal renal impairment if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if naproxen and esomeprazole magnesium delayed-release tablets treatment is needed in pregnant women, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue naproxen and esomeprazole magnesium delayed-release tablets and follow up according to clinical practice (see data). labor or delivery there are no studies on the effects of naproxen and esomeprazole magnesium delayed-release tablets during labor or delivery. in animal studies, nsaids, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data naproxen when used to delay preterm labor, inhibitors of prostaglandin synthesis, including nsaids such naproxen, may increase the risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage. naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin e levels in preterm infants. premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. esomeprazole esomeprazole is the s-isomer of omeprazole. four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to h2-receptor antagonists or other controls. a population-based retrospective cohort epidemiological study from the swedish medical birth registry, covering approximately 99% of pregnancies, from 1995-99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. the number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low apgar score, or hospitalization was similar to the number observed in this population. the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. a population-based retrospective cohort study covering all live births in denmark from 1996- 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837, 317 live births whose mothers did not use any proton pump inhibitor. the overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. a retrospective cohort study reported on 689 pregnant women exposed to either h2-blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. the overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an h2-blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% first trimester exposures). the reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. animal data there are no reproduction studies in animals with naproxen and esomeprazole magnesium delayed-release tablet, a combination of naproxen and esomeprazole. naproxen reproduction studies with naproxen administered during the period of organogenesis have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1500 mg/day based on body surface area comparison) rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.56 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of harm to the fetus due to the drug. esomeprazole no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis and have revealed no evidence of harm to the fetus due to esomeprazole magnesium. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development were performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times a daily human dose of 40 mg on a body surface area basis). neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg /kg/day (about 17 times an oral human dose of 40 mg on a body surface area basis). in addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times a daily human dose of 40 mg on a body surface area basis). physeal dysplasia in the femur was observed in offspring of rats treated with oral doses    of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times     the daily human dose of 40 mg on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in the pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg /kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis).  when rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). a pre- and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. a follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. risk summary limited data from published literature report that naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. esomeprazole is the s-isomer of omeprazole and limited data from published literature suggest omeprazole may be present in human milk. there is no information on the effects of naproxen or omeprazole on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for naproxen and esomeprazole magnesium delayed-release tablets and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, may delay or prevent rupture of ovarian follicles that may lead to reversible infertility in some women. small studies in women treated with nsaids have also shown a reversible delay in ovulation. published animal studies have shown that administration of prostaglandin synthesis inhibitors have the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. consider withdrawal of nsaids, including naproxen and esomeprazole magnesium delayed-release tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets have been established in adolescent patients 12 years of age and older weighing at least 38 kg for the symptomatic relief of jia and to decrease the risk of developing naproxen-associated gastric ulcers. use of naproxen and esomeprazole magnesium delayed-release tablets in this age group is based on extrapolation of adequate and well-controlled studies in adults and supported by a 6 month safety study including pharmacokinetic assessment of naproxen and esomeprazole magnesium in 36 adolescent patients with jia. based on the limited data, the plasma naproxen and plasma esomeprazole concentrations were found to be within the range to that observed to those found in healthy adults. the safety profile of naproxen and esomeprazole magnesium delayed-release tablets in adolescent patients with jia was similar to adults with ra. the safety and effectiveness of naproxen and esomeprazole magnesium delayed-release tablets in pediatric patients less than 12 years of age or less than 38 kg with jia have not been established. juvenile animal data in a juvenile rat toxicity study, esomeprazole was administered with both magnesium and strontium salts at oral doses about 34 to 68 times a daily human dose of 40 mg based on body surface area. increases in death were seen at the high dose, and at all doses of esomeprazole, there were decreases in body weight, body weight gain, femur weight and femur length, and decreases in overall growth [see nonclinical toxicology (13.2)]. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.14)] . of the total number of patients who received naproxen and esomeprazole magnesium delayed-release tablets (n=1157) in clinical trials, 387 were ≥65 years of age, of which 85 patients were 75 years and over. no meaningful differences in efficacy or safety were observed between these subjects and younger subjects [see adverse reactions (6)]. studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. as with other drugs used in the elderly, it is prudent to use the lowest effective dose [see dosage and administration  (2) , clinical pharmacology (12.3)]. experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nsaids. elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. most spontaneous reports of fatal gi events are in the geriatric population [see warnings and precautions (5.2)]. naproxen and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nsaids [see warnings and precautions (5.6)] . naproxen and esomeprazole magnesium delayed-release tablets should be avoided in patients with severe hepatic impairment because naproxen may increase the risk of renal failure or bleeding and esomeprazole doses should not exceed 20 mg daily in these patients [see dosage and administration (2), warnings and precautions (5.3 ), clinical pharmacology (12.3)] . naproxen-containing products, including naproxen and esomeprazole magnesium delayed-release tablets, are not recommended for use in patients with advanced renal disease [see dosage and administration (2), warnings and precautions (5.6 )] .

Stati Uniti - Ingliż - NLM (National Library of Medicine)

bryant ranch prepack - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole delayed-release capsules are indicated for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies (14.1)]. triple therapy: lansoprazole/amoxicillin/clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate h. pylori . eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole/amoxicillin lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months [see clinical studies (14.3)]. lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies (14.4)]. lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies (14.5)]. lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies (14.6)]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies ( 14.7) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole may be considered [see clinical studies (14.8)] lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies (14.9)] lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies (14.10)]. - lansoprazole delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6)]. - proton pump inhibitors (ppis), including lansoprazole, are contraindicated with rilpivirine-containing products [see drug interactions ( 7)]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole, refer to the contraindications section of their prescribing information. risk summary available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data) . in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data) . these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are 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. if lansoprazole delayed release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=1.04, [95% confidence interval (ci) 0.25-4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or)=1.12, [95% ci 0.86-1.45] and for spontaneous abortions or=1.29, [95% ci 0.84-1.97]). animal data no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules has been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole delayed-release capsules were not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data) . lansoprazole delayed-release capsules were not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo-controlled study. therefore, safety and effectiveness have not been established in patients less than one year of age. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. neonate to less than one year of age the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04- and 1.88-fold higher at doses of 0.5 mg/kg/day and 1 mg/kg/day, respectively). infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., non-pharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. one to 11 years of age in an uncontrolled, open-label, u.s. multicenter study, 66 pediatric patients (one to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole 15 mg daily if ≤30 kg or lansoprazole 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty-one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4 ). gerd final visit* % (n/n) 76% (47/62‡ ) 81% (22/27) 100% (27/27) in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ml at baseline to 97 pg/ml [interquartile range (25th to 75th percentile) of 71 to 130 pg/ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd 85% (56/66) took lansoprazole for 8 weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n=66) were constipation (5%) and headache (3%). twelve to 17 years of age in an uncontrolled, open-label, u.s. multicenter study, 87 adolescent patients (12 to 17 years of age) with symptomatic gerd were treated with lansoprazole for 8 to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive gerd and 23 (26%) erosive esophagitis (ee). the nonerosive gerd patients received lansoprazole 15 mg daily for eight weeks and the ee patients received lansoprazole 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during 8 weeks of lansoprazole treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole treatment. one patient remained unhealed after 12 weeks of treatment (table 5 ). gerd final visit % (n/n) 73.2% (60/82)† nonerosive gerd 71.2% (42/59)† erosive esophagitis improvement in overall gerd symptoms* 78.3% (18/23) healing rate‡ 95.5% (21/22)‡ in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25th to 75th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml.) the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with nonerosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. bone changes in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=21,486) in clinical studies of lansoprazole, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology ( 12.3)] . in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology ( 12.3)] . no dosage adjustment for lansoprazole is necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [see dosage and administration ( 2.3)].

Stati Uniti - Ingliż - NLM (National Library of Medicine)

bryant ranch prepack - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole delayed-release capsules are indicated for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies (14.1)]. triple therapy: lansoprazole/amoxicillin/clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate h. pylori . eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole/amoxicillin lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months [see clinical studies (14.3)]. lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies (14.4)]. lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies (14.5)]. lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies (14.6)]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies ( 14.7) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole may be considered [see clinical studies (14.8)] lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies (14.9)] lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies (14.10)]. - lansoprazole delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6)]. - proton pump inhibitors (ppis), including lansoprazole, are contraindicated with rilpivirine-containing products [see drug interactions ( 7)]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole, refer to the contraindications section of their prescribing information. risk summary available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data) . in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data) . these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are 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. if lansoprazole delayed release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=1.04, [95% confidence interval (ci) 0.25-4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or)=1.12, [95% ci 0.86-1.45] and for spontaneous abortions or=1.29, [95% ci 0.84-1.97]). animal data no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules has been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole delayed-release capsules were not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data) . lansoprazole delayed-release capsules were not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo-controlled study. therefore, safety and effectiveness have not been established in patients less than one year of age. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. neonate to less than one year of age the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04- and 1.88-fold higher at doses of 0.5 mg/kg/day and 1 mg/kg/day, respectively). infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., non-pharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. one to 11 years of age in an uncontrolled, open-label, u.s. multicenter study, 66 pediatric patients (one to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole 15 mg daily if ≤30 kg or lansoprazole 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty-one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4 ). gerd final visit* % (n/n) 76% (47/62‡ ) 81% (22/27) 100% (27/27) in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ml at baseline to 97 pg/ml [interquartile range (25th to 75th percentile) of 71 to 130 pg/ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd 85% (56/66) took lansoprazole for 8 weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n=66) were constipation (5%) and headache (3%). twelve to 17 years of age in an uncontrolled, open-label, u.s. multicenter study, 87 adolescent patients (12 to 17 years of age) with symptomatic gerd were treated with lansoprazole for 8 to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive gerd and 23 (26%) erosive esophagitis (ee). the nonerosive gerd patients received lansoprazole 15 mg daily for eight weeks and the ee patients received lansoprazole 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during 8 weeks of lansoprazole treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole treatment. one patient remained unhealed after 12 weeks of treatment (table 5 ). gerd final visit % (n/n) 73.2% (60/82)† nonerosive gerd 71.2% (42/59)† erosive esophagitis improvement in overall gerd symptoms* 78.3% (18/23) healing rate‡ 95.5% (21/22)‡ in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25th to 75th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml.) the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with nonerosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. bone changes in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=21,486) in clinical studies of lansoprazole, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology ( 12.3)] . in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology ( 12.3)] . no dosage adjustment for lansoprazole is necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [see dosage and administration ( 2.3)].

Stati Uniti - Ingliż - NLM (National Library of Medicine)

bryant ranch prepack - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole delayed-release capsules are indicated for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies (14.1)]. triple therapy: lansoprazole/amoxicillin/clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate h. pylori . eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole/amoxicillin lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.2)]. please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months [see clinical studies (14.3)]. lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies (14.4)]. lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies (14.5)]. lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies (14.6)]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies ( 14.7) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole may be considered [see clinical studies (14.8)] lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies (14.9)] lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies (14.10)]. - lansoprazole delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6)]. - proton pump inhibitors (ppis), including lansoprazole, are contraindicated with rilpivirine-containing products [see drug interactions ( 7)]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole, refer to the contraindications section of their prescribing information. risk summary available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data) . in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data) . these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are 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. if lansoprazole delayed release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=1.04, [95% confidence interval (ci) 0.25-4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or)=1.12, [95% ci 0.86-1.45] and for spontaneous abortions or=1.29, [95% ci 0.84-1.97]). animal data no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules has been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole delayed-release capsules were not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data) . lansoprazole delayed-release capsules were not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo-controlled study. therefore, safety and effectiveness have not been established in patients less than one year of age. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. neonate to less than one year of age the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04- and 1.88-fold higher at doses of 0.5 mg/kg/day and 1 mg/kg/day, respectively). infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., non-pharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. one to 11 years of age in an uncontrolled, open-label, u.s. multicenter study, 66 pediatric patients (one to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole 15 mg daily if ≤30 kg or lansoprazole 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty-one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4 ). gerd final visit* % (n/n) 76% (47/62‡ ) 81% (22/27) 100% (27/27) in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ml at baseline to 97 pg/ml [interquartile range (25th to 75th percentile) of 71 to 130 pg/ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd 85% (56/66) took lansoprazole for 8 weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n=66) were constipation (5%) and headache (3%). twelve to 17 years of age in an uncontrolled, open-label, u.s. multicenter study, 87 adolescent patients (12 to 17 years of age) with symptomatic gerd were treated with lansoprazole for 8 to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive gerd and 23 (26%) erosive esophagitis (ee). the nonerosive gerd patients received lansoprazole 15 mg daily for eight weeks and the ee patients received lansoprazole 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during 8 weeks of lansoprazole treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole treatment. one patient remained unhealed after 12 weeks of treatment (table 5 ). gerd final visit % (n/n) 73.2% (60/82)† nonerosive gerd 71.2% (42/59)† erosive esophagitis improvement in overall gerd symptoms* 78.3% (18/23) healing rate‡ 95.5% (21/22)‡ in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25th to 75th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml.) the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with nonerosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. bone changes in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=21,486) in clinical studies of lansoprazole, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology ( 12.3)] . in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology ( 12.3)] . no dosage adjustment for lansoprazole is necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [see dosage and administration ( 2.3)].

Stati Uniti - Ingliż - NLM (National Library of Medicine)

graviti pharmaceuticals private limited - esomeprazole magnesium (unii: r6dxu4way9) (esomeprazole - unii:n3pa6559ft) - adults esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed ee in adults. for those patients who have not healed after 4 to 8 weeks of treatment, an additional 4- to 8- week course of esomeprazole magnesium delayed-release capsules may be considered. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) for the healing of ee in pediatric patients 12 years to 17 years of age. esomeprazole magnesium delayed-release capsules are indicated for the maintenance of healing of ee in adults. controlled studies do not extend beyond 6 months. adults esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with gerd in adults. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 weeks) of heartburn and other symptoms associated with gerd in pediatric patients 12 years to 17 years of age. esomeprazole magnesium delayed-release capsules are indicated for the reduction in the occurrence of gastric ulcers associated with continuous nsaid therapy in adult patients at risk for developing gastric ulcers. patients are considered to be at risk due to their age (60 years and older) and/or documented history of gastric ulcers. controlled studies do not extend beyond 6 months. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy esomeprazole magnesium delayed-release capsules in combination with amoxicillin and clarithromycin is indicated for the treatment of adult patients with h. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate h. pylori . in patients who fail therapy, susceptibility testing should be done. if resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see clinical pharmacology (12.4) and the prescribing information for clarithromycin]. esomeprazole magnesium delayed-release capsules are indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome, in adults. - esomeprazole magnesium delayed-release capsules are contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6.2)]. - for information about contraindications of amoxicillin and clarithromycin, indicated in combination with esomeprazole magnesium delayed-release capsules for h. pylori eradication to reduce the risk of duodenal ulcer recurrence, refer to the contraindications section of the respective prescribing information. - proton pump inhibitors (ppis), including esomeprazole magnesium delayed-release capsules, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary there are no adequate and well-controlled studies with esomeprazole in pregnant women. esomeprazole is the s-isomer of omeprazole. available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see data) . reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole magnesium in rats and rabbits with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg (based on a body surface area basis for a 60 kg person). changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age (see data). the estimated background risks of major birth defects and miscarriage for the indicated population are 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. data human data esomeprazole is the s-isomer of omeprazole. four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to h2 -receptor antagonists or other controls. a population-based retrospective cohort epidemiological study from the swedish medical birth registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. the number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low apgar score, or hospitalization was similar to the number observed in this population. the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. a population-based retrospective cohort study covering all live births in denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. the overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. a retrospective cohort study reported on 689 pregnant women exposed to either h2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. the overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an h2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). the reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease paired controls. rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. animal data omeprazole reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. in rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. in rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. esomeprazole no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 41 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis. a pre-and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg on a body surface area basis). in addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times an oral human dose of 40 mg on a body surface area basis). physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in a pre-and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). when rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). a pre-and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. a follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. risk summary esomeprazole is the s-isomer of omeprazole and limited data suggest that omeprazole may be present in human milk. there are no clinical data on the effects of esomeprazole on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for esomeprazole magnesium and any potential adverse effects on the breastfed infant from esomeprazole magnesium or from the underlying maternal condition. healing of ee pediatric patients 1 year to 17 years of age the safety and effectiveness of esomeprazole magnesium delayed-release capsules have been established in pediatric patients 12 years to 17 years for short-term treatment (4 to 8 weeks) for healing of ee. use of esomeprazole for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. the safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.4)] . symptomatic gerd pediatric patients 1 year to 17 years of age the safety and effectiveness of esomeprazole delayed-release capsules have been established in pediatric patients 12 years to 17 years of age for the short-term treatment (4 weeks) of heartburn and other symptoms associated with gerd. use of esomeprazole for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. the safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.4)] . other conditions the safety and effectiveness of esomeprazole for the risk reduction of nsaid-associated gastric ulcer, h. pylori eradication to reduce the risk of duodenal ulcer recurrence and treatment of pathological hypersecretory conditions have not been established in pediatric patients. juvenile animal toxicity studies in a juvenile rat toxicity study, esomeprazole was administered with both magnesium and strontium salts at oral doses about 34 to 68 times a daily human dose of 40 mg based on body surface area. increases in death were seen at the high dose, and at all doses of esomeprazole, there were decreases in body weight, body weight gain, femur weight and femur length, and decreases in overall growth [see nonclinical toxicology (13.2)] . of the total number of patients who received esomeprazole magnesium delayed-release capsules in clinical trials, 1,459 were 65 to 74 years of age and 354 patients were 75 years of age and older. no overall differences in safety and efficacy were observed between the elderly and younger individuals, 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. in patients with severe hepatic impairment (child-pugh class c) exposure to esomeprazole substantially increased compared to healthy subjects. dosage modification of esomeprazole is recommended for patients with severe hepatic impairment for the healing of ee, risk reduction of nsaid-associated gastric ulcer, h. pylori eradication to reduce the risk of duodenal ulcer recurrence, and pathological hypersecretory conditions including zollinger-ellison syndrome [see dosage and administration (2.1), clinical pharmacology (12.3)] . in patients with mild to moderate liver impairment (child-pugh classes a and b), no dosage adjustment is necessary.