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hf acquisition co llc, dba healthfirst - amiodarone hydrochloride (unii: 976728sy6z) (amiodarone - unii:n3rq532iut) - nexterone is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (vf) and hemodynamically unstable ventricular tachycardia (vt) in patients refractory to other therapy. nexterone also can be used to treat patients with vt/vf for whom oral amiodarone is indicated, but who are unable to take oral medication. during or after treatment with nexterone, patients may be transferred to oral amiodarone therapy [see dosage and administration ( 2)]. use nexterone for acute treatment until the patient's ventricular arrhythmias are stabilized. most patients will require this therapy for 48 to 96 hours, but nexterone may be safely administered for longer periods if necessary. nexterone is contraindicated in patients with: • known hypersensitivity to any of the components of nexterone premixed injection, including iodine. hypersensitivity reactions may involve rash, angioedema, cutaneous/mucosal hemorrhage (bleeding), fever, arthralgias (joint pains), eosinophilia (abnormal blood counts), uritcaria (hives), thrombotic thrombocytopenic purpura, or severe periarteritis (inflammation around blood vessels). • cardiogenic shock. • marked sinus bradycardia. • second- or third-degree atrio-ventricular (av) block unless a functioning pacemaker is available. 8.1 pregnancy pregnancy category d [see warnings and precautions ( 5-5.8)]. teratogenic effects amiodarone and desethylamiodarone cross the placenta. reported risks include: • neonatal bradycardia, qt prolongation, and periodic ventricular extrasystoles • neonatal hypothyroidism (with or without goiter) detected antenatally or in the newborn and reported even after a few days of exposure • neonatal hyperthyroxinemia • neurodevelopmental abnormalities independent of thyroid function, including speech delay and difficulties with written language and arithmetic, delayed motor development, and ataxia. • jerk nystagmus with synchronous head titubation • fetal growth retardation • premature birth amiodarone has caused a variety of adverse effects in animals. amiodarone was given intravenously to rabbits at dosages of 5, 10, or 25 mg/kg per day (about 0.1, 0.3, and 0.7 times human intravenous maintenance dose of 0.5 mg/min on a body surface area basis), during gestation days 8 to 16 (organogenesis). the incidence of maternal deaths increased with increasing dose and occurred in all treated groups and controls. mean fetal weights were significantly decreased in the low and middle dose groups and embryotoxicity (as manifested by fewer full-term fetuses and increased resorptions) occurred at dosages of 10 mg/kg and above. there were no significant differences in the number of minor fetal abnormalities and no major fetal abnormalities were observed. amiodarone was administered by continuous intravenous infusion to rats at dosages of 25, 50, or 100 mg/kg per day (about 0.3, 0.7 and 1.3 times the human intravenous maintenance dose of 0.5 mg/min on a body surface area basis) during gestation days 8 to 16 (organogenesis). maternal toxicity (manifest as reduced weight gain and food consumption) and embryotoxicity (manifest as increased resorptions, decreased live litter size and fetal body weights, and delayed sternal and metacarpal ossification) were observed in the 100 mg/kg group. the delayed ossification was reversible and related to decreased fetal weight. fetal thyroid tissues appeared normal in all groups. nonteratogenic effects very high concentrations of amiodarone and desethylamiodarone may be found in testes. an elevated follicle-stimulating hormone and luteinizing hormone levels, suggestive of testicular dysfunction, have been reported in men on long-term amiodarone treatment. while planning pregnancy after discontinuation of amiodarone treatment, consider the long half-life of amiodarone and its metabolite dea. 8.2 labor and delivery it is not known whether the use of amiodarone during labor or delivery has any immediate or delayed adverse effects. preclinical studies in rodents have not shown any effect on the duration of gestation or on parturition. 8.3 nursing mothers amiodarone and one of its major metabolites, desethylamiodarone (dea), are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the drug. nursing offspring of lactating rats administered amiodarone have demonstrated reduced viability and transient reduced body weight gains. the risk of exposing the infant to amiodarone and dea must be weighed against the potential benefit of arrhythmia suppression in the mother. advise the mother to discontinue nursing. 8.4 pediatric use the safety and effectiveness of amiodarone in pediatric patients have not been established; therefore, the use of amiodarone in pediatric patients is not recommended. in a pediatric trial of 61 patients, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and av block (15%) were common dose-related adverse reactions and were severe or life-threatening in some cases. injection site reactions were seen in 5 (25%) of the 20 patients receiving intravenous amiodarone through a peripheral vein irrespective of dose regimen. 8.5 geriatric use clinical studies of amiodarone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. carefully consider dose selection in an elderly patient. in general, start at the low end of the dosing range in the elderly to reflect the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

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hf acquisition co llc, dba healthfirst - ondansetron (unii: 4af302esos) (ondansetron - unii:4af302esos) - ondansetron orally disintegrating tablets are indicated for the prevention of nausea and vomiting associated with: highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2 initial and repeat courses of moderately emetogenic cancer chemotherapy radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen ondansetron orally disintegrating tablets also indicated for the prevention of postoperative nausea and/or vomiting. ondansetron orally disintegrating tablets are contraindicated in patients: known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see adverse reactions (6.2)] receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness 8.1 pregnancy risk summary available data do not reliably inform the association of ondansetron and adverse fetal outcomes. published epidemiological studies on the association between ondansetron and fetal outcomes have reported inconsistent findings and have important methodological limitations hindering interpretation (see data). reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area, respectively (see data). the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data human data methodological limitations of the epidemiology studies preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of ondansetron in pregnancy. two large retrospective cohort studies of ondansetron use in pregnancy have been published. in one study with 1,349 infants born to women who reported the use of ondansetron or received an ondansetron prescription in the first trimester, no increased risk for major congenital malformations was seen in aggregate analysis. in this same study, however, a sub-analysis for specific malformations reported an association between ondansetron exposure and cardiovascular defect (odds ratio (or) 1.62 [95% ci (1.04, 2.14)]) and cardiac septal defect (or 2.05 [95% ci (1.19, 3.28)]). the second study examined 1970 women who received ondansetron prescription during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage or stillbirth, and infants of low-birth weight or small for gestational age. important methodological limitations with these studies include the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, and other unadjusted confounders that may account for the study findings. a case-control study evaluating associations between several common non-cardiac malformations and multiple antiemetic drugs reported an association between maternal use of ondansetron and isolated cleft palate (reported adjusted or = 2.37 [95% ci (1.18, 4.76)]). however, this association could be a chance finding, given the large number of drugs-birth defect comparisons in this study. it is unknown whether ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation (the palate is formed between the 6th and 9th weeks of pregnancy) or whether mothers of infants with cleft palate used other medications or had other risk factors for cleft palate in the offspring. in addition, no cases of isolated cleft palate were identified in the aforementioned 2 large retrospective cohort studies. at this time, there is no clear evidence that ondansetron exposure in early pregnancy can cause cleft palate. animal data in embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis. with the exception of a slight decrease in maternal body weight gain in the rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. at doses of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal exposure margin was approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on body surface area. in a pre- and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up to 15 mg/kg/day from day 17 of pregnancy to litter day 21. with the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre- and postnatal development of their offspring, including reproductive performance of the mated f1 generation. at a dose of 15 mg/kg/day in rats, the maternal exposure margin was approximately 6 times the maximum recommended human oral dose of 24 mg/day, based on body surface area. 8.2 lactation risk summary it is not known whether ondansetron is present in human milk. there are no data on the effects of ondansetron on the breastfed infant or the effects on milk production. however, it has been demonstrated that ondansetron is present in the milk of rats. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ondansetron and any potential adverse effects on the breast fed infant from ondansetron or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of orally administered ondansetron have been established in pediatric patients 4 years and older for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. use of ondansetron in these age-groups is supported by evidence from adequate and well- controlled studies of ondansetron in adults with additional data from 3 open-label, uncontrolled, non-u.s. trials in 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens [see dosage and administration (2.2), clinical studies (14.1)]. additional information on the use of ondansetron in pediatric patients may be found in ondansetron injection prescribing information. the safety and effectiveness of orally administered ondansetron have not been established in pediatric patients for: prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy prevention of nausea and vomiting associated with radiotherapy prevention of postoperative nausea and/or vomiting 8.5 geriatric use of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in u.s.- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older. no overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects. a reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see clinical pharmacology (12.3)]. there were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dosage adjustment is needed in elderly patients. 8.6 hepatic impairment no dosage adjustment is needed in patients with mild or moderate hepatic impairment. in patients with severe hepatic impairment, clearance is reduced and the apparent volume of distribution is increased, resulting in a significant increase in the half-life of ondansetron. therefore, do not exceed a total daily dose of 8 mg in patients with severe hepatic impairment (child-pugh score of 10 or greater) [see dosage and administration (2.2), clinical pharmacology (12.3)]. 8.7 renal impairment no dosage adjustment is recommended for patients with any degree of renal impairment (mild, moderate, or severe). there is no experience beyond first-day administration of ondansetron [see clinical pharmacology (12.3)]. animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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hf acquisition co llc, dba healthfirst - ondansetron hydrochloride (unii: nmh84ozk2b) (ondansetron - unii:4af302esos) - prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy ondansetron injection is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin. ondansetron is approved for patients aged 6 months and older. prevention of postoperative nausea and/or vomiting ondansetron injection is indicated for the prevention of postoperative nausea and/or vomiting. as with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. in patients in whom nausea and/or vomiting must be avoided postoperatively, ondansetron injection is recommended even when the incidence of postoperative nausea and/or vomiting is low. for patients who do not receive prophylactic ondansetron injection and experience nausea and/or vomiting postoperatively, ondansetron injection may be given to prevent further episodes. ondansetron is approved for patients aged 1 month and older. ondansetron injection is contraindicated for patients known to have hypersensitivity (e.g., anaphylaxis) to this product or any of its components. anaphylactic reactions have been reported in patients taking ondansetron [see adverse reactions (6.2)]. the concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron. 8.1 pregnancy risk summary available data do not reliably inform the association of ondansetron and adverse fetal outcomes. published epidemiological studies on the association between ondansetron and fetal outcomes have reported inconsistent findings and have important methodological limitations hindering interpretation [see data]. reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered intravenously during organogenesis at approximately 3.6 and 2.9 times the maximum recommended human intravenous dose of 0.15 mg/kg given three times a day, based on body surface area, respectively [see data]. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the us general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data methodological limitations of the epidemiology studies preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of ondansetron in pregnancy. two large retrospective cohort studies of ondansetron use in pregnancy have been published. in one study with 1,349 infants born to women who reported the use of ondansetron or received an ondansetron prescription in the first trimester, no increased risk for major congenital malformations was seen in aggregate analysis. in this same study, however, a sub-analysis for specific malformations reported an association between ondansetron exposure and cardiovascular defect (odds ratio (or) 1.62 [95% ci (1.04, 2.14)]) and cardiac septal defect (or 2.05 [95% ci (1.19, 3.28)]). the second study examined 1970 women who received ondansetron prescription during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage or stillbirth, and infants of low birth weight or small for gestational age. important methodological limitations with these studies include the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, and other unadjusted confounders that may account for the study findings. a case-control study evaluating associations between several common non-cardiac malformations and multiple antiemetic drugs reported an association between maternal use of ondansetron and isolated cleft palate (reported adjusted or = 2.37 [95% ci (1.18, 4.76)]). however, this association could be a chance finding, given the large number of drugs-birth defect comparisons in this study. it is unknown whether ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation (the palate is formed between the 6th and 9th weeks of pregnancy) or whether mothers of infants with cleft palate used other medications or had other risk factors for cleft palate in the offspring. in addition, no cases of isolated cleft palate were identified in the aforementioned two large retrospective cohort studies. at this time, there is no clear evidence that ondansetron exposure in early pregnancy can cause cleft palate. animal data in embryo-fetal development studies in rats and rabbits, pregnant animals received intravenous doses of ondansetron up to 10 mg/kg/day and 4 mg/kg/day, respectively, during the period of organogenesis. with the exception of short periods of maternal weight loss and a slight increase in the incidence of early uterine deaths at the high dose level in rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. at doses of 10 mg/kg/day in rats and 4 mg/kg/day in rabbits, the maternal exposure margin was approximately 3.6 and 2.9 times the maximum recommended human oral dose of 0.15 mg/kg given three times a day, respectively, based on body surface area. no intravenous pre-and post-natal developmental toxicity study was performed with ondansetron. in an oral pre-and postnatal development study pregnant rats received doses of ondansetron up to 15 mg/kg/day from day 17 of pregnancy to litter day 21. with the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre-and postnatal development of their offspring, including reproductive performance of the mated f1 generation. 8.2 lactation risk summary it is not known whether ondansetron is present in human milk. there are no data on the effects of ondansetron on the breastfed infant or the effects on milk production. however, it has been demonstrated that ondansetron is present in the milk of rats. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ondansetron and any potential adverse effects on the breastfed infant from ondansetron or from the underlying maternal condition. 8.4 pediatric use little information is available about the use of ondansetron in pediatric surgical patients younger than 1 month [see clinical studies (14.2)]. little information is available about the use of ondansetron in pediatric cancer patients younger than 6 months [see clinical studies (14.1), dosage and administration (2)]. the clearance of ondansetron in pediatric patients aged 1 month to 4 months is slower and the half-life is ~2.5-fold longer than patients who are aged >4 to 24 months. as a precaution, it is recommended that patients younger than 4 months receiving this drug be closely monitored [see clinical pharmacology (12.3)]. 8.5 geriatric use of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting us- and foreign-controlled clinical trials, 862 were aged 65 years and older. no overall differences in safety or effectiveness were observed between subjects 65 years and older and younger subjects. a reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see clinical pharmacology (12.3)]. there were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. 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. dosage adjustment is not needed in patients over the age of 65. 8.6 hepatic impairment in patients with severe hepatic impairment (child-pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life [see clinical pharmacology (12.3)]. in such patients, a total daily dose of 8 mg should not be exceeded [see dosage and administration (2.3)]. 8.7 renal impairment although plasma clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 ml/min), no dosage adjustment is recommended [see clinical pharmacology (12.3)]. animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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

hf acquisition co llc, dba healthfirst - ondansetron hydrochloride (unii: nmh84ozk2b) (ondansetron - unii:4af302esos) - ondansetron tablets are indicated for the prevention of nausea and vomiting associated with: highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2 . initial and repeat courses of moderately emetogenic cancer chemotherapy. radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen ondansetron tablets are also indicated for the prevention of postoperative nausea and/or vomiting. ondansetron is contraindicated in patients: 1. known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see adverse reactions ( 6.2)] 2. receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness 8.1 pregnancy risk summary available data do not reliably inform the association of ondansetron and adverse fetal outcomes. published epidemiological studies on the association between ondansetron and fetal outcomes have reported inconsistent findings and have important methodological limitations hindering interpretation (see data). reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area, respectively [see data]. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the us general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data human data methodological limitations of the epidemiology studies preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of ondansetron in pregnancy. two large retrospective cohort studies of ondansetron use in pregnancy have been published. in one study with 1,349 infants born to women who reported the use of ondansetron or received an ondansetron prescription in the first trimester, no increased risk for major congenital malformations was seen in aggregate analysis. in this same study, however, a sub-analysis for specific malformations reported an association between ondansetron exposure and cardiovascular defect (odds ratio (or) 1.62 [95% ci (1.04, 2.14)]) and cardiac septal defect (or 2.05 [95% ci (1.19, 3.28)]). the second study examined 1970 women who received ondansetron prescription during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage or stillbirth, and infants of low-birth weight or small for gestational age. important methodological limitations with these studies include the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, and other unadjusted confounders that may account for the study findings. a case-control study evaluating associations between several common non-cardiac malformations and multiple antiemetic drugs reported an association between maternal use of ondansetron and isolated cleft palate (reported adjusted or = 2.37 [95% ci (1.18, 4.76)]). however, this association could be a chance finding, given the large number of drugs-birth defect comparisons in this study. it is unknown whether ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation (the palate is formed between the 6th and 9th weeks of pregnancy) or whether mothers of infants with cleft palate used other medications or had other risk factors for cleft palate in the offspring. in addition, no cases of isolated cleft palate were identified in the aforementioned 2 large retrospective cohort studies. at this time, there is no clear evidence that ondansetron exposure in early pregnancy can cause cleft palate. animal data in embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis. with the exception of a slight decrease in maternal body weight gain in the rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. at doses of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal exposure margin was approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on body surface area. in a pre-and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up to 15 mg/kg/day from day 17 of pregnancy to litter day 21. with the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre-and postnatal development of their offspring, including reproductive performance of the mated f1 generation. at a dose of 15 mg/kg/day in rats, the maternal exposure margin was approximately 6 times the maximum recommended human oral dose of 24 mg/day, based on body surface area. 8.2 lactation risk summary it is not known whether ondansetron is present in human milk. there are no data on the effects of ondansetron on the breastfed infant or the effects on milk production. however, it has been demonstrated that ondansetron is present in the milk of rats. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ondansetron and any potential adverse effects on the breast fed infant from ondansetron or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of orally administered ondansetron have been established in pediatric patients 4 years and older for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. use of ondansetron in these age-groups is supported by evidence from adequate and well-controlled studies of ondansetron in adults with additional data from 3 open-label, uncontrolled, non-us trials in 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens [see dosage and administration ( 2.2), clinical studies ( 14.1)]. additional information on the use of ondansetron in pediatric patients may be found in ondansetron injection prescribing information. the safety and effectiveness of orally administered ondansetron have not been established in pediatric patients for: • prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy • prevention of nausea and vomiting associated with radiotherapy • prevention of postoperative nausea and/or vomiting 8.5 geriatric use of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in us-and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older. no overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects. a reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see clinical pharmacology ( 12.3)]. there were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dosage adjustment is needed in elderly patients. 8.6 hepatic impairment no dosage adjustment is needed in patients with mild or moderate hepatic impairment. in patients with severe hepatic impairment, clearance is reduced and the apparent volume of distribution is increased, resulting in a significant increase in the half-life of ondansetron. therefore, do not exceed a total daily dose of 8 mg in patients with severe hepatic impairment (child-pugh score of 10 or greater) [see dosage and administration ( 2.2), clinical pharmacology ( 12.3)]. 8.7 renal impairment no dosage adjustment is recommended for patients with any degree of renal impairment (mild, moderate, or severe). there is no experience beyond first-day administration of ondansetron [see clinical pharmacology ( 12.3)]. animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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bayer ag -

United Kingdom - English - myHealthbox

bayer ag -

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

hf acquisition co llc, dba healthfirst - acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - acetaminophen injection is indicated for the management of mild to moderate pain in adult and pediatric patients 2 years and older the management of moderate to severe pain with adjunctive opioid analgesics in adult and pediatric patients 2 years and older the reduction of fever in adult and pediatric patients. acetaminophen is contraindicated: in patients with known hypersensitivity to acetaminophen or to any of the excipients in the intravenous formulation. in patients with severe hepatic impairment or severe active liver disease [see warnings and precautions (5.1)]. 8.1 pregnancy risk summary published epidemiological studies with oral acetaminophen use during pregnancy have not reported a clear association with acetaminophen use and birth defects, miscarriage, or adverse maternal or fetal outcomes [see data]. animal reproduction studies have not been conducted with iv acetaminophen. reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen. treatment of pregnant rats with doses of acetaminophen approximately equal to the maximum human daily dose (mhdd) showed evidence of fetotoxicity and increases in bone variations in the fetuses. in another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately equal to the mhdd. in mice and rats treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproductive capacity were reported. in mice, a reduction in number of litters of the parental mating pair was observed as well as retarded growth, abnormal sperm in their offspring and reduced birth weight in the next generation. in rats, female fertility was decreased following in utero exposure to acetaminophen [see data]. the estimated background risk of major birth defects and miscarriages 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. data human data the results from a large population-based prospective cohort, including data from 26,424 women with live born singletons who were exposed to oral acetaminophen during the first trimester, indicate no increased risk for congenital malformations, compared to a control group of unexposed children. the rate of congenital malformations (4.3%) was similar to the rate in the general population. a population-based, case-control study from the national birth defects prevention study showed that 11,610 children with prenatal exposure to acetaminophen during the first trimester had no increased risk of major birth defects compared to 4,500 children in the control group. other epidemiological data showed similar results. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including recall bias. animal data studies in pregnant rats that received oral acetaminophen during organogenesis at doses up to 0.85 times the maximum human daily dose (mhdd = 4 grams/day, based on a body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose-related increase in bone variations (reduced ossification and rudimentary rib changes). offspring had no evidence of external, visceral, or skeletal malformations. when pregnant rats received oral acetaminophen throughout gestation at doses of 1.2 times the mhdd (based on a body surface area comparison), areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses. these effects did not occur in animals that received oral acetaminophen at doses 0.3 times the mhdd, based on a body surface area comparison. in a continuous breeding study, pregnant mice received 0.25, 0.5, or 1.0% acetaminophen via the diet (357, 715, or 1,430 mg/kg/day). these doses are approximately 0.43, 0.87, and 1.7 times the mhdd, respectively, based on a body surface area comparison. a dose related reduction in body weights of fourth and fifth litter offspring of the treated mating pair occurred during lactation and post-weaning at all doses. animals in the high dose group had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next generation pups. 8.2 lactation risk summary there is no information regarding the presence of acetaminophen in human milk, the effects on the breastfed infant, or the effects on milk production. however, limited published studies report that acetaminophen passes rapidly into human milk with similar levels in the milk and plasma. average and maximum neonatal doses of 1% and 2%, respectively, of the weight-adjusted maternal dose are reported after a single oral administration of 1 gram apap. there is one well-documented report of a rash in a breast-fed infant that resolved when the mother stopped acetaminophen use and recurred when she resumed acetaminophen use. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for acetaminophen and any potential adverse effects on the breastfed infant from acetaminophen or from the underlying maternal condition. 8.3 females and males of reproductive potential based on animal data use of acetaminophen may cause reduced fertility in males and females of reproductive potential. it is not known whether these effects on fertility are reversible. published animal studies reported that oral acetaminophen treatment of male animals at doses that are 1.2 times the mhdd and greater (based on a body surface area comparison) result in decreased testicular weights, reduced spermatogenesis, and reduced fertility. in female animals given the same doses, reduced implantation sites were reported. additional published animal studies indicate that acetaminophen exposure in utero adversely impacts reproductive capacity of both male and female offspring at clinically relevant exposures [see nonclinical toxicology (13.1)]. 8.4 pediatric use treatment of acute pain the safety and effectiveness of acetaminophen for the treatment of acute pain in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of acetaminophen in adults and safety and pharmacokinetic data from adult and 483 pediatric patients across all age groups [see dosage and administration (2.3) and pharmacokinetics (12.3)]. the effectiveness of acetaminophen for the treatment of acute pain in pediatric patients younger than 2 years of age has not been established. in patients younger than 2 years, efficacy was not demonstrated in a double-blind, placebo-controlled study of 198 pediatric patients younger than 2 years. pediatric patients less than 2 years of age, including neonates from 28 to 40 weeks gestational age at birth, were randomized to receive opioid plus acetaminophen or opioid plus placebo. no difference in analgesic effect of intravenous acetaminophen, measured by assessment of reduced need for additional opioid treatment for pain control was observed. treatment of fever the safety and effectiveness of acetaminophen for the treatment of fever in pediatric patients, including premature neonates born at ≥ 32 weeks gestational age is supported by adequate and well-controlled studies of acetaminophen in adults, clinical studies in 244 pediatric patients 2 years and older, and safety and pharmacokinetic data from 239 patients younger than 2 years including neonates ≥ 32 weeks gestational age. 8.5 geriatric use of the total number of subjects in clinical studies of acetaminophen, 15% were age 65 and over, while 5% were age 75 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. 8.6 patients with hepatic impairment acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease [ see warnings and precautions (5.1) and clinical pharmacology (12)]. a reduced total daily dose of acetaminophen may be warranted. 8.7 patients with renal impairment in cases of severe renal impairment (creatinine clearance ≤ 30 ml/min), longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted.

Malta - English - Medicines Authority

clonmel healthcare limited waterford road, clonmel, co. tipperary e91 d768, ireland - gastro-resistant hard capsule - dimethyl fumarate 120 mg - immunosuppressants

Malta - English - Medicines Authority

clonmel healthcare limited waterford road, clonmel, co. tipperary e91 d768, ireland - gastro-resistant hard capsule - dimethyl fumarate 240 mg - immunosuppressants

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

ravensdown fertiliser co-operative limited - cypermethrin - insecticide - barley | broccoli | brussels sprouts | cabbage | cauliflower | chinese cabbage | cotton | field pea | kale (chou moellier) | koh - armyworm - mythimna spp. | armyworm - persectania spp. | cabbage moth | cabbage white butterfly | cluster caterpillar | common armyworm - mythimna convecta | corn earworm | cotton budworm or bollworm | grey cluster bug | helicoverpa spp. | native budworm or bollworm | pea weevil | plague thrips | rutherglen bug | sorghum midge | southern or barley armyworm | soybean looper | tobacco budworm | tomato grub | barley armyworm | barley grub | corn earworm | cotton bollworm | diachrysia orichalceaa | diamondback moth | heliothis | leucania convecta | native bollworm | native budworm | southern armyworm | tobacco budworm | tomato grub