Yhdysvallat - englanti - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - lamotrigine (unii: u3h27498ks) (lamotrigine - unii:u3h27498ks) - lamotrigine 5 mg - lamotrigine tablets for oral suspension (chewable, dispersible tablets) are indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: lamotrigine tablets for oral suspension (chewable, dispersible tablets) are indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (aed). safety and effectiveness of lamotrigine tablets for oral suspension (chewable, dispersible tablets) have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from aeds other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant aeds. lamotrigine tablets for oral suspension (chewable, dispersible tablets) are indicated for the maintenance treatment of bipolar i disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see clinical studies (14.2)] . limitations of use treatment of acute manic or mixed episodes is not recommended. effectiveness of lamotrigine tablets for oral suspension (chewable, dispersible tablets) in the acute treatment of mood episodes has not been established. lamotrigine is contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see boxed warning, warnings and precautions (5.1, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including lamotrigine, during pregnancy. encourage women who are taking lamotrigine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population (see data) . the majority of lamotrigine pregnancy exposure data are from women with epilepsy. in animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations as with other aeds, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. there have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-pregnancy concentrations after delivery. dose adjustments may be necessary to maintain clinical response. data human data: data from several international pregnancy registries have not shown an increased risk for malformations overall. the international lamotrigine pregnancy registry reported major congenital malformations in 2.2% (95% ci: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. the naaed pregnancy registry reported major congenital malformations among 2.0% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. eurap, a large international pregnancy registry focused outside of north america, reported major birth defects in 2.9% (95% ci: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester. the frequency of major congenital malformations was similar to estimates from the general population. the naaed pregnancy registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% ci: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. this finding has not been observed in other large international pregnancy registries. furthermore, a case-control study based on 21 congenital anomaly registries covering over 10 million births in europe reported an adjusted odds ratio for isolated oral clefts with lamotrigine exposure of 1.45 (95% ci: 0.8, 2.63). several meta-analyses have not reported an increased risk of major congenital malformations following lamotrigine exposure in pregnancy compared with healthy and disease-matched controls. no patterns of specific malformation types were observed. the same meta-analyses evaluated the risk of additional maternal and infant outcomes including fetal death, stillbirth, preterm birth, small for gestational age, and neurodevelopmental delay. although there are no data suggesting an increased risk of these outcomes with lamotrigine monotherapy exposure, differences in outcome definition, ascertainment methods, and comparator groups limit the conclusions that can be drawn. animal data: when lamotrigine was administered to pregnant mice, rats, or rabbits during the period of organogenesis (oral doses of up to 125, 25, and 30 mg/kg, respectively), reduced fetal body weight and increased incidences of fetal skeletal variations were seen in mice and rats at doses that were also maternally toxic. the no-effect doses for embryofetal developmental toxicity in mice, rats, and rabbits (75, 6.25, and 30 mg/kg, respectively) are similar to (mice and rabbits) or less than (rats) the human dose of 400 mg/day on a body surface area (mg/m2 ) basis. in a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities were observed in exposed offspring at both doses. the lowest effect dose for developmental neurotoxicity in rats is less than the human dose of 400 mg/day on a mg/m2 basis. maternal toxicity was observed at the higher dose tested. when pregnant rats were administered lamotrigine (oral doses of 0, 5, 10, or 20 mg/kg) during the latter part of gestation and throughout lactation, increased offspring mortality (including stillbirths) was seen at all doses. the lowest effect dose for pre- and post-natal developmental toxicity in rats is less than the human dose of 400 mg/day on a mg/m2 basis. maternal toxicity was observed at the 2 highest doses tested. when administered to pregnant rats, lamotrigine decreased fetal folate concentrations at doses greater than or equal to 5 mg/kg/day, which is less than the human dose of 400 mg/day on a mg/m2 basis. risk summary lamotrigine is present in milk from lactating women taking lamotrigine tablets (see data) . neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after delivery to the pre-pregnancy dosage. glucuronidation is required for drug clearance. glucuronidation capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure. events including rash, apnea, drowsiness, poor sucking, and poor weight gain (requiring hospitalization in some cases) have been reported in infants who have been human milk-fed by mothers using lamotrigine; whether or not these events were caused by lamotrigine is unknown. no data are available on the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lamotrigine and any potential adverse effects on the breastfed infant from lamotrigine or from the underlying maternal condition. clinical considerations human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine. measurement of infant serum levels should be performed to rule out toxicity if concerns arise. human milk-feeding should be discontinued in infants with lamotrigine toxicity. data data from multiple small studies indicate that lamotrigine plasma levels in nursing infants have been reported to be as high as 50% of maternal plasma concentrations. epilepsy lamotrigine is indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of lennox-gastaut syndrome, and pgtc seizures. safety and efficacy of lamotrigine used as adjunctive treatment for partial-onset seizures were not demonstrated in a small, randomized, double-blind, placebo-controlled withdrawal trial in very young pediatric patients (aged 1 to 24 months). lamotrigine was associated with an increased risk for infectious adverse reactions (lamotrigine 37%, placebo 5%), and respiratory adverse reactions (lamotrigine 26%, placebo 5%). infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. respiratory adverse reactions included nasal congestion, cough, and apnea. bipolar disorder safety and efficacy of lamotrigine for the maintenance treatment of bipolar disorder were not established in a double-blind, randomized withdrawal, placebo-controlled trial that evaluated 301 pediatric patients aged 10 to 17 years with a current manic/hypomanic, depressed, or mixed mood episode as defined by dsm-iv-tr. in the randomized phase of the trial, adverse reactions that occurred in at least 5% of patients taking lamotrigine (n = 87) and were twice as common compared with patients taking placebo (n = 86) were influenza (lamotrigine 8%, placebo 2%), oropharyngeal pain (lamotrigine 8%, placebo 2%), vomiting (lamotrigine 6%, placebo 2%), contact dermatitis (lamotrigine 5%, placebo 2%), upper abdominal pain (lamotrigine 5%, placebo 1%), and suicidal ideation (lamotrigine 5%, placebo 0%). juvenile animal data in a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as adults) were observed at the 2 highest doses. the no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m2 basis. clinical trials of lamotrigine for epilepsy and bipolar disorder did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. experience in patients with hepatic impairment is limited. based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see clinical pharmacology (12.3)] , the following general recommendations can be made. no dosage adjustment is needed in patients with mild liver impairment. initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. escalation and maintenance doses may be adjusted according to clinical response [see dosage and administration (2.1)]. lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. in a small study comparing a single dose of lamotrigine in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was approximately twice as long in the subjects with chronic renal failure [see clinical pharmacology (12.3)] . initial doses of lamotrigine should be based on patients’ aed regimens; reduced maintenance doses may be effective for patients with significant renal impairment. few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. because there is inadequate experience in this population, lamotrigine should be used with caution in these patients [see dosage and administration (2.1)] .

Yhdysvallat - englanti - NLM (National Library of Medicine)

biomarin pharmaceutical inc. - sapropterin dihydrochloride (unii: rg277lf5b3) (sapropterin - unii:egx657432i) - sapropterin dihydrochloride 100 mg - kuvan® is indicated to reduce blood phenylalanine (phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (hpa) due to tetrahydrobiopterin- (bh4-) responsive phenylketonuria (pku). kuvan is to be used in conjunction with a phe-restricted diet. none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to kuvan during pregnancy. for more information regarding the registry program call 1-800-983-4587. risk summary available pregnancy registry data  have not reported an  association with kuvan and major birth defects, miscarriage, or adverse maternal or fetal outcomes when kuvan was used during pregnancy (see data) . an embryo-fetal development study with sapropterin dihydrochloride in rats using oral doses up to 3 times the maximum recommended human dose (mrhd) given during the period of organogenesis showed no effects. in a rabbit study using oral administration of sapropterin dihydrochloride dur

Yhdysvallat - englanti - NLM (National Library of Medicine)

aurobindo pharma limited - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets /amoxicillin/clarithromycin lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets /amoxicillin lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets 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 orally   disintegrating   tablets 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 orally   disintegrating   tablets 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 orally   disintegrating   tablets may be considered [see clinical studies (14.8)] . lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets are contraindicated in patients with known 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 orally disintegrating tablets, 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 orally disintegrating tablets, 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 orally disintegrating tablets 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 orally disintegrating tablets and any potential adverse effects on the breastfed child from lansoprazole delayed-release orally disintegrating tablets or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets 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. 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 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 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. 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 delayed-release orally disintegrating tablets 15 mg daily if ≤30 kg or lansoprazole delayed-release orally disintegrating tablets 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release orally disintegrating tablets 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 orally disintegrating tablets 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). in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole delayed-release orally disintegrating tablets 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%). twelve years to 17 years of age 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). 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). 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 delayed-release orally disintegrating tablets 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 (lan soe′ pra zole) delayed-release orally disintegrating tablets important: -   take lansoprazole delayed-release orally disintegrating tablets before meals. -   do not crush or chew lansoprazole delayed-release orally disintegrating tablets. -   lansoprazole delayed-release orally disintegrating tablets should only be used with the foods and juices listed below. lansoprazole delayed-release orally disintegrating tablets - do not chew, crush, cut or break the tablets. - put the tablet on the tongue and let it dissolve, with or without water. - swallow after the tablet dissolves. - the tablet usually dissolves in less than 1 minute. for patients who have trouble swallowing tablets, lansoprazole delayed-release orally disintegrating tablets can be given as follows: giving lansoprazole delayed-release orally disintegrating tablets with water using an oral syringe: - put a 15 mg tablet in an oral syringe and draw up 4 ml of water into the oral syringe, or put a 30 mg tablet in an oral syringe and draw up 10 ml of water into the oral syringe. - gently shake the oral syringe to mix the tablet and the water. - after the tablet is mixed in the water, place the tip of the oral syringe in the mouth. give the medicine within 15 minutes of mixing. do not save the tablet and water mixture for later use. - refill the oral syringe with about 2 ml of water for the 15 mg tablet or 5 ml of water for the 30 mg tablet, and shake gently. place the tip of the oral syringe in the mouth and give the medicine that is left in the syringe. giving lansoprazole delayed-release orally disintegrating tablets with water through a nasogastric tube (ng tube) size 8 french or larger: - put a 15 mg tablet in a catheter-tip syringe and draw up 4 ml of water, or put a 30 mg tablet in a catheter-tip syringe and draw up 10 ml of water. - gently shake the catheter-tip syringe to mix the tablet and the water. - connect the catheter-tip syringe to the ng tube. - give the mixture right away through the ng tube that goes into the stomach. give the medicine within 15 minutes of mixing. do not save the granule and water mixture for later use. - refill the catheter-tip syringe with about 5 ml of water and shake gently. flush the ng tube with the water. how should i store lansoprazole delayed-release orally disintegrating tablets? - store lansoprazole delayed-release orally disintegrating tablets at room temperature between 20° to 25°c (68° to 77°f). keep lansoprazole delayed-release orally disintegrating tablets   and all medicines out of the reach of children. this instruction for use has been approved by the u.s. food and drug administration. the brands listed are trademarks of their respective owners and are not trademarks of aurobindo pharma limited.   distributed by: aurobindo pharma usa, inc. 279 princeton-hightstown road east windsor, nj 08520 manufactured by: aurobindo pharma limited hyderabad-500 032, india revised: 04/2024

Uusi-Seelanti - englanti - Medsafe (Medicines Safety Authority)

viatris limited - erythromycin ethylsuccinate 46.8 mg/ml equivalent to erythromycin 40 mg/ml (does not include 10% overage) - granules for oral suspension - 200 mg/5ml - active: erythromycin ethylsuccinate 46.8 mg/ml equivalent to erythromycin 40 mg/ml (does not include 10% overage) excipient: aspartame cherry flavour 163837 colloidal silicon dioxide erythrosine propylene glycol alginate sodium benzoate sodium citrate dihydrate sorbitol - streptococcus pyogenes (group a beta-haemolytic streptococcus): upper and lower respiratory tract, skin and soft tissue infections of mild to moderate severity. when oral medication is preferred for treatment of streptococcal pharyngitis and in long term prophylaxis of rheumatic fever, erythromycin is an alternate drug of choice. when oral medication is given, the importance of strict adherence by the patient to the prescribed dosage regimen must be stressed. a therapeutic dose should be administered for at least 10 days. prevention of initial attacks of rheumatic fever: penicillin is considered to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of group a beta-haemolytic streptococcal infections of the upper respiratory tract e.g. tonsillitis or pharyngitis). erythromycin is indicated for the treatment of penicillin-allergic patients. the therapeutic dose should be administered for 10 days. prevention of recurrent attacks of rheumatic fever: penicillin or sulphonamides are considered to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. in patients who are allergic to penicillin and sulphonamides, oral erythromycin is recommended in the long term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever).

Uusi-Seelanti - englanti - Medsafe (Medicines Safety Authority)

viatris limited - erythromycin ethylsuccinate 93.6 mg/ml equivalent to erythromycin 80 mg/ml (does not include 10% overage) - granules for oral suspension - 400 mg/5ml - active: erythromycin ethylsuccinate 93.6 mg/ml equivalent to erythromycin 80 mg/ml (does not include 10% overage) excipient: aspartame cherry flavour 163837 colloidal silicon dioxide erythrosine propylene glycol alginate sodium benzoate sodium citrate dihydrate sorbitol - streptococcus pyogenes (group a beta-haemolytic streptococcus): upper and lower respiratory tract, skin and soft tissue infections of mild to moderate severity. when oral medication is preferred for treatment of streptococcal pharyngitis and in long term prophylaxis of rheumatic fever, erythromycin is an alternate drug of choice. when oral medication is given, the importance of strict adherence by the patient to the prescribed dosage regimen must be stressed. a therapeutic dose should be administered for at least 10 days. prevention of initial attacks of rheumatic fever: penicillin is considered to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of group a beta-haemolytic streptococcal infections of the upper respiratory tract e.g. tonsillitis or pharyngitis). erythromycin is indicated for the treatment of penicillin-allergic patients. the therapeutic dose should be administered for 10 days. prevention of recurrent attacks of rheumatic fever: penicillin or sulphonamides are considered to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. in patients who are allergic to penicillin and sulphonamides, oral erythromycin is recommended in the long term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever).

Yhdysvallat - englanti - NLM (National Library of Medicine)

aurobindo pharma limited - montelukast sodium (unii: u1o3j18sfl) (montelukast - unii:mhm278sd3e) - montelukast 4 mg - montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older. montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 6 years of age and older. montelukast sodium is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 2 years of age and older. because the benefits of montelukast sodium may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions (5.1)] , reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium is not indicated for the treatment of an acute asthma attack. montelukast sodium is contraindicated in patients with hypersensitivity to any of its components. risk summary    available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see data] . in animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (mrhdod) based on aucs [see data]. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age. data human data published data from prospective and retrospective cohort studies have not identified an association with montelukast sodium use during pregnancy and major birth defects. available studies have methodologic limitations, including small sample size, in some cases retrospective data collection, and inconsistent comparator groups. animal data in embryo-fetal development studies, montelukast administered to pregnant rats and rabbits during organogenesis (gestation days 6 to 17 in rats and 6 to 18 in rabbits) did not cause any adverse developmental effects at maternal oral doses up to 400 and 300 mg/kg/day in rats and rabbits, respectively (approximately 100 and 110 times the auc in humans at the mrhdod, respectively).      risk summary a published clinical lactation study reports the presence of montelukast in human milk. data available on the effects of the drug on infants, either directly [see use in specific populations (8.4)] or through breast milk, do not suggest a significant risk of adverse reactions from exposure to montelukast sodium. the effects of the drug on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for montelukast sodium and any potential adverse reactions on the breastfed infant from montelukast sodium or from the underlying maternal condition. safety and effectiveness of montelukast sodium for asthma have been established in pediatric patients 6 to 14 years of age. use of montelukast sodium for this indication is supported by evidence from well-controlled studies. safety and efficacy data in this age group are similar to those seen in adults [see adverse reactions (6.1), clinical pharmacology, specific populations (12.3), and clinical studies (14.1, 14.2)]. the effectiveness of montelukast sodium for the treatment of seasonal allergic rhinitis in pediatric patients 2 to 14 years of age and for the treatment of perennial allergic rhinitis in pediatric patients 2 to 14 years of age have been established and is supported by extrapolation from the demonstrated effectiveness in patients 15 years of age and older with allergic rhinitis as well as the assumption that the disease course, pathophysiology and the drug’s effect are substantially similar among these populations. the safety of montelukast sodium chewable tablets 4 mg in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data [see adverse reactions (6.1)] . effectiveness of montelukast sodium in this age group is extrapolated from the demonstrated effectiveness in patients 6 years of age and older with asthma and is based on similar pharmacokinetic data, as well as the assumption that the disease course, pathophysiology and the drug’s effect are substantially similar among these populations. effectiveness in this age group is supported by exploratory efficacy assessments from a large, well-controlled safety study conducted in patients 2 to 5 years of age. the safety of montelukast sodium chewable tablets 4 mg and 5 mg in pediatric patients aged 2 to 14 years with allergic rhinitis is supported by data from studies conducted in pediatric patients aged 2 to 14 years with asthma. a safety study in pediatric patients 2 to 14 years of age with seasonal allergic rhinitis demonstrated a similar safety profile [see adverse reactions (6.1)] .    the safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established. growth rate in pediatric patients a 56-week, multi-center, double-blind, randomized, active- and placebo-controlled parallel group study was conducted to assess the effect of montelukast sodium on growth rate in 360 patients with mild asthma, aged 6 to 8 years. treatment groups included montelukast 5 mg once daily, placebo, and beclomethasone dipropionate administered as 168 mcg twice daily with a spacer device. for each subject, a growth rate was defined as the slope of a linear regression line fit to the height measurements over 56 weeks. the primary comparison was the difference in growth rates between montelukast sodium and placebo groups. growth rates, expressed as least-squares (ls) mean (95% ci) in cm/year, for the montelukast sodium, placebo, and beclomethasone treatment groups were 5.67 (5.46, 5.88), 5.64 (5.42, 5.86), and 4.86 (4.64, 5.08), respectively. the differences in growth rates, expressed as least-squares (ls) mean (95% ci) in cm/year, for montelukast sodium minus placebo, beclomethasone minus placebo, and montelukast sodium minus beclomethasone treatment groups were 0.03 (-0.26, 0.31), -0.78 (-1.06, -0.49); and 0.81 (0.53, 1.09), respectively. growth rate (expressed as mean change in height over time) for each treatment group is shown in figure 1. of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. the pharmacokinetic profile and the oral bioavailability of a single 10 mg oral dose of montelukast are similar in elderly and younger adults. the plasma half-life of montelukast is slightly longer in the elderly. no dosage adjustment in the elderly is required. no dosage adjustment is recommended in patients with mild-to-moderate hepatic insufficiency [see clinical pharmacology (12.3)]. no dosage adjustment is recommended in patients with renal insufficiency [see clinical pharmacology (12.3)].

Yhdysvallat - englanti - NLM (National Library of Medicine)

dr.reddy's laboratories limited - montelukast sodium (unii: u1o3j18sfl) (montelukast - unii:mhm278sd3e) - montelukast 10 mg - montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older. montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 6 years of age and older. montelukast sodium is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 2 years of age and older. because the benefits of montelukast sodium may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions ( 5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium is not indicated for the treatment of an acute asthma attack. montelukast sodium is contraindicated in patients with hypersensitivity to any of its components. risk summary available data from published prospective and retrospective cohort studies over decades with

Yhdysvallat - englanti - NLM (National Library of Medicine)

macleods pharmaceuticals limited - montelukast (unii: mhm278sd3e) (montelukast - unii:mhm278sd3e) - montelukast 4 mg - montelukast sodium chewable tablet is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older. montelukast sodium chewable tablet is indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 6 years of age and older. montelukast sodium chewable tablet is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 2 years of age and older. because the benefits of montelukast sodium chewable tablets may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions (5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium chewable tablet is not indicated for the treatment of an acute asthma attack. montelukast sodium chewable tablets is contraindicated in patients with hypersensitivity to any of its components. risk su

Yhdysvallat - englanti - NLM (National Library of Medicine)

unichem pharmaceuticals (usa), inc. - montelukast sodium (unii: u1o3j18sfl) (montelukast - unii:mhm278sd3e) - montelukast 10 mg - montelukast sodium  is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older. montelukast sodium  is indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 6 years of age and older. montelukast sodium  is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 2 years of age and older. because the benefits of montelukast sodium may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions (5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium is not indicated for the treatment of an acute asthma attack.. montelukast sodium is contraindicated in patients with hypersensitivity to any of its components. risk summary available data from published prospective and retrospective cohort studies over decades

Yhdysvallat - englanti - NLM (National Library of Medicine)

macleods pharmaceuticals limited - zolmitriptan (unii: 2fs66th3yw) (zolmitriptan - unii:2fs66th3yw) - zolmitriptan 2.5 mg - zolmitriptan is indicated for the acute treatment of migraine with or without aura in adults. limitations of use - only use zolmitriptan if a clear diagnosis of migraine has been established. if a patient has no response to zolmitriptan treatment for the first migraine attack, reconsider the diagnosis of migraine before zolmitriptan are administered to treat any subsequent attacks. - zolmitriptan is not indicated for the prevention of migraine attacks.  - safety and effectiveness of zolmitriptan have not been established for cluster headache. zolmitriptan is contraindicated in patients with: - ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), other significant underlying cardiovascular disease, or coronary artery vasospasm including prinzmetal's angina [see warnings and precautions (5.1) ]. - wolff-parkinson-white syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see warnings and precautions (