Irlanti - englanti - HPRA (Health Products Regulatory Authority)

apotex europe b.v. - voriconazole - film coated tablet - 50 milligram - voriconazole - antimycotics for systemic use, triazole derivatives - voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows: treatment of invasive aspergillosis. treatment of candidemia in non-neutropenic patients. treatment of fluconazole-resistant serious invasive candida infections (including c. krusei). treatment of serious fungal infections caused by scedosporium spp. and fusarium spp. voriconazole apotex should be administered primarily to patients with progressive, possibly life-threatening infections. prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (hsct) recipients

Irlanti - englanti - HPRA (Health Products Regulatory Authority)

apotex europe b.v. - voriconazole - film coated tablet - 200 milligram - voriconazole - antimycotics for systemic use, triazole derivatives - voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows: treatment of invasive aspergillosis. treatment of candidemia in non-neutropenic patients. treatment of fluconazole-resistant serious invasive candida infections (including c. krusei). treatment of serious fungal infections caused by scedosporium spp. and fusarium spp. voriconazole apotex should be administered primarily to patients with progressive, possibly life-threatening infections. prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (hsct) recipients

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole tablets are indicated for the treatment of: - schizophrenia [see clinical studies (14.1)] -  irritability associated with autistic disorder [see clinical studies (14.4)]  - treatment of tourette’s disorder [see clinical studies (14.5)]  additional pediatric use information is approved for otsuka america pharmaceutical, inc.’s abilify®  (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. aripiprazole tablets are contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)] . pregnancy exposure registry   there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/.   risk summary   neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations). overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data). there are risks to the mother associated with untreated schizophrenia, other indication and with exposure to antipsychotics, including aripiprazole, during pregnancy (see clinical considerations).   in animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 19 times, respectively, the maximum recommended human dose (mrhd) of 30 mg/day based on mg/m2 body surface area, produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses 10 times the mrhd based on mg/m2 body surface area, produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (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   there is a risk to the mother from untreated schizophrenia other indication, including increased risk of relapse, hospitalization, and suicide. schizophrenia and other indication are associated with increased adverse perinatal outcomes, including preterm birth. it is not known if this is a direct result of the illness or other comorbid factors.   a prospective, longitudinal study followed 201 pregnant women with a history of other indication who were euthymic and taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.   fetal/neonatal adverse reactions   extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. these symptoms have varied in severity. monitor neonates for extrapyramidal and/or withdrawal symptoms, and manage symptoms appropriately. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.   data   human data   published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. a retrospective study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects.   animal data   in animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits.   in pregnant rats treated orally with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are approximately 1, 3 and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area, a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes, were observed at 10 times the mrhd. delayed skeletal ossification was observed at 3 and 10 times the mrhd. delivered offspring had increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed at 10 times the mrhd (the other dose groups were not examined for these findings). postnatally, delayed vaginal opening was seen at 3 and 10 times the mrhd. impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) were observed at 10 times the mrhd; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. in pregnant rats injected intravenously with aripiprazole during organogenesis at doses of 3 mg/kg/day, 9 mg/kg/day, and 27 mg/kg/day, which are 1, 3, and 9 times the mrhd of 30 mg/day based on mg/m2 body surface area, decreased fetal weight and delayed skeletal ossification were observed at 9 times the mrhd; this dose also caused maternal toxicity. in pregnant rabbits treated orally with aripiprazole during organogenesis at doses of 10, 30, and 100 mg/kg/day which are 6, 19, and 65 times the mrhd of 30 mg/day based on mg/m2 body surface area, decreased maternal food consumption, and increased abortions as well as increased fetal mortality were observed at 65 times the mhrd. decreased fetal weight and increased incidence of fused sternebrae were observed at 19 and 65 times the mrhd. in pregnant rabbits injected intravenously with aripiprazole during organogenesis at doses of 3 mg/kg/day, 10 mg/kg/day, and 30 mg/kg/day, which are 2, 6, and 19 times the mrhd of 30 mg/day based on mg/m2  body surface area, decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification were observed at 19 times the mrhd; this dose also caused maternal toxicity. the fetal no-effect dose was 10 mg/kg/day, which is 6 times the mrhd. in rats treated orally with aripiprazole peri- and post-natally from gestation day 17 through postpartum day 21 at doses of 3, 10, and 30 mg/kg/day which are 1, 3, and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area slight maternal toxicity and slightly prolonged gestation were observed at 10 times the mhrd. an increase in stillbirths and, decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. in rats injected intravenously with aripiprazole from gestation day 6 through lactation day 20 at doses of 3 mg/kg/day, 8 mg/kg/day, and 20 mg/kg/day, which are 1, 3, and 6 times the mrhd of 30 mg/day based on mg/m2  body surface area, increased stillbirths were observed at 3 and 6 times the mrhd; and decreases in early postnatal pup weight and survival were observed at 6 times the mrhd; these doses also caused some maternal toxicity. there were no effects on postnatal behavioral and reproductive development. risk summary   limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole.   the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for aripiprazole and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition. safety and effectiveness in pediatric patients with agitation associated with schizophrenia or other indication have not been established. the pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients, 10 to 17 years of age, were similar to those in adults after correcting for the differences in body weight [see clinical pharmacology (12.3)] . schizophrenia safety and effectiveness in pediatric patients with schizophrenia were established in a 6-week, placebo-controlled clinical trial in 202 pediatric patients aged 13 to 17 years [see dosage and administration (2.1), adverse reactions (6.1) , and clinical studies (14.1)] . although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. irritability associated with autistic disorder safety and effectiveness in pediatric patients demonstrating irritability associated with autistic disorder were established in two 8-week, placebo-controlled clinical trials in 212 pediatric patients aged 6 to 17 years [see indications and usage (1), dosage and administration (2.4), adverse reactions (6.1), and clinical studies (14.4)]. a maintenance trial was conducted in pediatric patients (6 to 17 years of age) with irritability associated with autistic disorder. the first phase of this trial was an open-label, flexibly dosed (aripiprazole 2 to 15 mg/day) phase in which patients were stabilized (defined as > 25% improvement on the abc-i subscale, and a cgi-i rating of “much improved” or “very much improved”) on aripiprazole for 12 consecutive weeks. overall, 85 patients were stabilized and entered the second, 16-week, double-blind phase where they were randomized to either continue aripiprazole treatment or switch to placebo. in this trial, the efficacy of aripiprazole for the maintenance treatment of irritability associated with autistic disorder was not established. tourette’s disorder safety and effectiveness of aripiprazole in pediatric patients with tourette’s disorder were established in one 8-week (aged 7 to 17) and one 10-week trial (aged 6 to 18) in 194 pediatric patients [see dosage and administration (2.5), adverse reactions (6.1), and clinical studies (14.5)]. maintenance efficacy in pediatric patients has not been systematically evaluated. information describing a clinical study in which efficacy was not demonstrated in patients ages 6 to 17 years is approved for otsuka america pharmaceutical, inc.’s abilify® (aripiprazole). additional pediatric use information in patients ages 6 to 18 years is approved for otsuka america pharmaceutical, inc.’s abilify® (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. juvenile animal studies aripiprazole in juvenile rats caused mortality, cns clinical signs, impaired memory and learning, and delayed sexual maturation when administered at oral doses of 10, 20, 40 mg/kg/day from weaning (21 days old) through maturity (80 days old). at 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other cns signs were observed in both genders. in addition, delayed sexual maturation was observed in males. at all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. the changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. a no observed adverse effect level (noael) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2-month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. aripiprazole in juvenile dogs (2 months old) caused cns clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. a noael could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2-month recovery period. no dosage adjustment is recommended for elderly patients [see boxed warning, warnings and precautions (5.1), and clinical pharmacology (12.3)] . of the 13,543 patients treated with oral aripiprazole in clinical trials, 1073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. placebo-controlled studies of oral aripiprazole in schizophrenia, or other indications did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 　 aripiprazole is not approved for the treatment of patients with psychosis associated with alzheimer’s disease [see boxed warning and warnings and precautions (5.1)] . dosage adjustment is recommended in known cyp2d6 poor metabolizers due to high aripiprazole concentrations. approximately 8% of caucasians and 3–8% of black/african americans cannot metabolize cyp2d6 substrates and are classified as poor metabolizers (pm) [see dosage and administration (2.7) and clinical pharmacology (12.3)]. no dosage adjustment for aripiprazole is required on the basis of a patient’s hepatic function (mild to severe hepatic impairment, child-pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 ml/minute) [see clinical pharmacology (12.3)]. no dosage adjustment for aripiprazole is required on the basis of a patient’s sex, race, or smoking status [see clinical pharmacology (12.3)]. aripiprazole is not a controlled substance. aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). in physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. while the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - gemfibrozil (unii: q8x02027x3) (gemfibrozil - unii:q8x02027x3) - gemfibrozil 600 mg - gemfibrozil tablets are indicated as adjunctive therapy to diet for: - treatment of adult patients with very high elevations of serum triglyceride levels (types iv and v hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. patients who present such risk typically have serum triglycerides over 2000 mg/dl and have elevations of vldl-cholesterol as well as fasting chylomicrons (type v hyperlipidemia). subjects who consistently have total serum or plasma triglycerides below 1000 mg/dl are unlikely to present a risk of pancreatitis. gemfibrozil therapy may be considered for those subjects with triglyceride elevations between 1000 and 2000 mg/dl who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. it is recognized that some type iv patients with triglycerides under 1000 mg/dl may, through dietary or alcoholic indiscretion, convert to a type v pattern with massive triglyceride elevations accompanying

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - azelastine hydrochloride (unii: 0l591qr10i) (azelastine - unii:zqi909440x) - azelastine hydrochloride 0.5 mg in 1 ml - azelastine hydrochloride ophthalmic solution is indicated for the treatment of itching of the eye associated with allergic conjunctivitis. azelastine hydrochloride ophthalmic solution is contraindicated in persons with known or suspected hypersensitivity to any of its components.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - atomoxetine hydrochloride (unii: 57wvb6i2w0) (atomoxetine - unii:asw034s0b8) - atomoxetine 10 mg - atomoxetine capsules are indicated for the treatment of attention-deficit/hyperactivity disorder (adhd). the efficacy of atomoxetine capsules was established in seven clinical trials in outpatients with adhd: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15) [see clinical studies (14)] . a diagnosis of adhd (dsm-iv) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years. the symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home. the symptoms must not be better accounted for by another mental disorder. the specific etiology of adhd is unknown, and there is no single diagnostic test. adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. learning may or may not be impaired. the diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of dsm-iv characteristics. for the inattentive type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful. for the hyperactive-impulsive type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go,” excessive talking, blurting answers, can’t wait turn, intrusive. for a combined type diagnosis, both inattentive and hyperactive-impulsive criteria must be met. atomoxetine is indicated as an integral part of a total treatment program for adhd that may include other measures (psychological, educational, social) for patients with this syndrome. drug treatment may not be indicated for all patients with this syndrome. drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. appropriate educational placement is essential in children and adolescents with this diagnosis and psychosocial intervention is often helpful. when remedial measures alone are insufficient, the decision to prescribe drug treatment medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms. atomoxetine capsules are contraindicated in patients known to be hypersensitive to atomoxetine or other constituents of the product [see warnings and precautions (5.8)] . atomoxetine should not be taken with an maoi, or within 2 weeks after discontinuing an maoi. treatment with an maoi should not be initiated within 2 weeks after discontinuing atomoxetine. with other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an maoi. some cases presented with features resembling neuroleptic malignant syndrome. such reactions may occur when these drugs are given concurrently or in close proximity [see drug interactions (7.1)] . in clinical trials, atomoxetine use was associated with an increased risk of mydriasis and therefore its use is not recommended in patients with narrow angle glaucoma. serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received atomoxetine. therefore, atomoxetine should not be taken by patients with pheochromocytoma or a history of pheochromocytoma. atomoxetine should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experience increases in blood pressure or heart rate that could be clinically important (for example, 15 to 20 mm hg in blood pressure or 20 beats per minute in heart rate) [see warnings and precautions (5.4)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including atomoxetine, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. risk summary available published studies with atomoxetine use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. some animal reproduction studies of atomoxetine had adverse developmental outcomes. one of 3 studies in pregnant rabbits dosed during organogenesis resulted in decreased live fetuses and an increase in early resorptions, as well as slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery. these effects were observed at plasma levels (auc) 3 times and 0.4 times the human plasma levels in extensive and poor metabolizers receiving the maximum recommended human dose (mrhd), respectively. in rats dosed prior to mating and during organogenesis a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at a dose approximately 5 times the mrhd on a mg/m2 basis. in one of 2 studies in which rats were dosed prior to mating through the periods of organogenesis and lactation, decreased pup weight and decreased pup survival were observed at doses corresponding to 5-6 times the mrhd on a mg/m2 basis. no adverse fetal effects were seen in pregnant rats dosed during the organogenesis period (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 2-4% and 15-­20%, respectively. data animal data pregnant rabbits were treated with up to 100 mg/kg/day of atomoxetine by gavage throughout the period of organogenesis. at this dose, in 1 of 3 studies, a decrease in live fetuses and an increase in early resorptions was observed. slight increases in the incidences of atypical origin of carotid artery and absent subclavian artery were observed. these findings were observed at doses that caused slight maternal toxicity. the no-effect dose for these findings was 30 mg/kg/day. the 100 mg/kg dose is approximately 23 times the mrhd on a mg/m2 basis; plasma levels (auc) of atomoxetine at this dose in rabbits are estimated to be 3.3 times (extensive metabolizers) or 0.4 times (poor metabolizers) those in humans receiving the mrhd. rats were treated with up to approximately 50 mg/kg/day of atomoxetine (approximately 6 times the mrhd on a mg/m2 basis) in the diet from 2 weeks (females) or 10 weeks (males) prior to mating through the periods of organogenesis and lactation. in 1 of 2 studies, decreases in pup weight and pup survival were observed. the decreased pup survival was also seen at 25 mg/kg (but not at 13 mg/kg). in a study in which rats were treated with atomoxetine in the diet from 2 weeks (females) or 10 weeks (males) prior to mating throughout the period of organogenesis, a decrease in fetal weight (female only) and an increase in the incidence of incomplete ossification of the vertebral arch in fetuses were observed at 40 mg/kg/day (approximately 5 times the mrhd on a mg/m2 basis) but not at 20 mg/kg/day. no adverse fetal effects were seen when pregnant rats were treated with up to 150 mg/kg/day (approximately 17 times the mrhd on a mg/m2 basis) by gavage throughout the period of organogenesis. risk summary there are no data on the presence of atomoxetine or its metabolite in human milk, the effects on the breastfed child, or the effects on milk production. atomoxetine is present in animal milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for atomoxetine and any potential adverse effects on the breastfed child from atomoxetine or from the underlying maternal condition. anyone considering the use of atomoxetine in a child or adolescent must balance the potential risks with the clinical need [see boxed warning and warnings and precautions (5.1)] . the pharmacokinetics of atomoxetine in children and adolescents are similar to those in adults. the safety, efficacy, and pharmacokinetics of atomoxetine in pediatric patients less than 6 years of age have not been evaluated. a study was conducted in young rats to evaluate the effects of atomoxetine on growth and neurobehavioral and sexual development. rats were treated with 1, 10, or 50 mg/kg/day (approximately 0.2, 2, and 8 times, respectively, the maximum human dose on a mg/m2 basis) of atomoxetine given by gavage from the early postnatal period (day 10 of age) through adulthood. slight delays in onset of vaginal patency (all doses) and preputial separation (10 and 50 mg/kg), slight decreases in epididymal weight and sperm number (10 and 50 mg/kg), and a slight decrease in corpora lutea (50 mg/kg) were seen, but there were no effects on fertility or reproductive performance. a slight delay in onset of incisor eruption was seen at 50 mg/kg. a slight increase in motor activity was seen on day 15 (males at 10 and 50 mg/kg and females at 50 mg/kg) and on day 30 (females at 50 mg/kg) but not on day 60 of age. there were no effects on learning and memory tests. the significance of these findings to humans is unknown. the safety, efficacy and pharmacokinetics of atomoxetine in geriatric patients have not been evaluated. atomoxetine exposure (auc) is increased, compared with normal subjects, in em subjects with moderate (child-pugh class b) (2-fold increase) and severe (child-pugh class c) (4-fold increase) hepatic insufficiency. dosage adjustment is recommended for patients with moderate or severe hepatic insufficiency [see dosage and administration (2.3)] . em subjects with end stage renal disease had higher systemic exposure to atomoxetine than healthy subjects (about a 65% increase), but there was no difference when exposure was corrected for mg/kg dose. atomoxetine can therefore be administered to adhd patients with end stage renal disease or lesser degrees of renal insufficiency using the normal dosing regimen. gender did not influence atomoxetine disposition. ethnic origin did not influence atomoxetine disposition (except that pms are more common in caucasians). tics in patients with adhd and comorbid tourette’s disorder — atomoxetine administered in a flexible dose range of 0.5 to 1.5 mg/kg/day (mean dose of 1.3 mg/kg/day) and placebo were compared in 148 randomized pediatric (age 7 to 17 years) subjects with a dsm-iv diagnosis of adhd and comorbid tic disorder in an 18 week, double-blind, placebo-controlled study in which the majority (80%) enrolled in this trial with tourette’s disorder (tourette’s disorder: 116 subjects; chronic motor tic disorder: 29 subjects). a non-inferiority analysis revealed that atomoxetine did not worsen tics in these patients as determined by the yale global tic severity scale total score (ygtss). out of 148 patients who entered the acute treatment phase, 103 (69.6%) patients discontinued the study. the primary reason for discontinuation in both the atomoxetine (38 of 76 patients, 50.0%) and placebo (45 of 72 patients, 62.5%) treatment groups was identified as lack of efficacy with most of the patients discontinuing at week 12. this was the first visit where patients with a cgi-s≥4 could also meet the criteria for “clinical non-responder” (cgi-s remained the same or increased from study baseline) and be eligible to enter an open-label extension study with atomoxetine. there have been postmarketing reports of tics [see adverse reactions (6.2)] . anxiety in patients with adhd and comorbid anxiety disorders – in two post-marketing, double-blind, placebo-controlled trials, it has been demonstrated that treating patients with adhd and comorbid anxiety disorders with atomoxetine does not worsen their anxiety. in a 12-week double-blind, placebo-controlled trial, 176 patients, aged 8-17, who met dsm-iv criteria for adhd and at least one of the anxiety disorders of separation anxiety disorder, generalized anxiety disorder or social phobia were randomized. following a 2-week double-blind placebo lead-in, atomoxetine was initiated at 0.8 mg/kg/day with increase to a target dose of 1.2 mg/kg/day (median dose 1.30 mg/kg/day +/- 0.29 mg/kg/day). atomoxetine did not worsen anxiety in these patients as determined by the pediatric anxiety rating scale (pars). of the 158 patients who completed the double-blind placebo lead-in, 26 (16%) patients discontinued the study. in a separate 16-week, double-blind, placebo-controlled trial, 442 patients aged 18 to 65, who met dsm-iv criteria for adult adhd and social anxiety disorder (23% of whom also had generalized anxiety disorder) were randomized. following a 2-week double-blind placebo lead-in, atomoxetine was initiated at 40 mg/day to a maximum dose of 100 mg/day (mean daily dose 83 mg/day +/- 19.5 mg/day). atomoxetine did not worsen anxiety in these patients as determined by the liebowitz social anxiety scale (lsas). of the 413 patients who completed the double-blind placebo lead-in, 149 (36.1%) patients discontinued the study. there have been postmarketing reports of anxiety [see adverse reactions (6.2)] . atomoxetine is not a controlled substance. in a randomized, double-blind, placebo-controlled, abuse-potential study in adults comparing effects of atomoxetine and placebo, atomoxetine was not associated with a pattern of response that suggested stimulant or euphoriant properties. clinical study data in over 2000 children, adolescents, and adults with adhd and over 1200 adults with depression showed only isolated incidents of drug diversion or inappropriate self-administration associated with atomoxetine. there was no evidence of symptom rebound or adverse reactions suggesting a drug-discontinuation or withdrawal syndrome. animal experience — drug discrimination studies in rats and monkeys showed inconsistent stimulus generalization between atomoxetine and cocaine.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - acyclovir (unii: x4hes1o11f) (acyclovir - unii:x4hes1o11f) - acyclovir 200 mg - acyclovir capsule is indicated for the acute treatment of herpes zoster (shingles). acyclovir capsule is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. acyclovir capsule is indicated for the treatment of chickenpox (varicella). acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - olopatadine hydrochloride (unii: 2xg66w44kf) (olopatadine - unii:d27v6190pm) - olopatadine hydrochloride ophthalmic solution, 0.1% is indicated for the treatment of the signs and symptoms of allergic conjunctivitis. olopatadine hydrochloride ophthalmic solution, 0.1 % is contraindicated in persons with a known hypersensitivity to olopatadine hydrochloride or any components of olopatadine hydrochloride ophthalmic solution, 0.1%.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - pentoxifylline (unii: sd6qct3tsu) (pentoxifylline - unii:sd6qct3tsu) - pentoxifylline extended-release tablets are indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. pentoxifylline can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease. pentoxifylline should not be used in patients with recent cerebral and/or retinal hemorrhage or in patients who have previously exhibited intolerance to this product or methylxanthines such as caffeine, theophylline, and theobromine.

Yhdysvallat - englanti - NLM (National Library of Medicine)

apotex corp. - butorphanol tartrate (unii: 2l7i72ruhn) (butorphanol - unii:qv897jc36d) - butorphanol tartrate 10 mg in 1 ml - butorphanol tartrate nasal spray is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use : because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration [see warnings] reserve butorphanol tartrate nasal spray for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): - have not been tolerated or are not expected to be tolerated, - have not provided adequate analgesia or are not expected to provide adequate analgesia butorphanol tartrate nasal spray should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. butorphanol tartrate nasal spray is contraindicated in: - patients with significant respiratory depression [see warnings] - patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings] - patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings] - patients with hypersensitivity to butorphanol tartrate, the preservative benzethonium chloride, or any of the formulation excipients (e.g., anaphylaxis) [see warnings]) controlled substance butorphanol tartrate nasal spray contains butorphanol, a schedule iv controlled substance.   abuse butorphanol tartrate nasal spray contains butorphanol tartrate, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings].   misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.   drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.   misuse and abuse of butorphanol tartrate nasal spray increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of butorphanol tartrate nasal spray with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction.   all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of butorphanol tartrate nasal spray abuse include those with a history of prolonged use of any opioid, including products containing butorphanol tartrate, those with a history of drug or alcohol abuse, or those who use butorphanol tartrate nasal spray in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.     butorphanol tartrate nasal spray, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.   proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.   risks specific to abuse of butorphanol tartrate nasal spray abuse of butorphanol tartrate nasal spray poses a risk of overdose and death. the risk is increased with concurrent use of butorphanol tartrate nasal spray with alcohol and/or other cns depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv.   dependence both tolerance and physical dependence can develop during use of opioid therapy.   tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).   physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.   withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.   do not abruptly discontinue butorphanol tartrate nasal spray in a patient physically dependent on opioids. rapid tapering of butorphanol tartrate nasal spray in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.   when discontinuing butorphanol tartrate nasal spray, gradually taper the dosage using a patient-specific plan that considers the following: the dose of butorphanol tartrate nasal spray the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration, and warnings].   infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see  pregnancy].