Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - labetalol hydrochloride (unii: 1gev3baw9j) (labetalol - unii:r5h8897n95) - labetalol hydrochloride 100 mg - labetalol hydrochloride tablets usp are indicated in the management of hypertension. labetalol hydrochloride tablets usp may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics. labetalol hydrochloride is contraindicated in bronchial asthma, overt cardiac failure, greater-than-first-degree heart block, cardiogenic shock, severe bradycardia, other conditions associated with severe and prolonged hypotension, and in patients with a history of hypersensitivity to any component of the product (see warnings). beta-blockers, even those with apparent cardioselectivity, should not be used in patients with a history of obstructive airway disease, including asthma.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - lorazepam (unii: o26fzp769l) (lorazepam - unii:o26fzp769l) - lorazepam 0.5 mg - lorazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. the effectiveness of lorazepam tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. lorazepam tablets are contraindicated in patients with - hypersensitivity to benzodiazepines or to any components of the formulation. - acute narrow-angle glaucoma.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - alprazolam (unii: yu55mq3izy) (alprazolam - unii:yu55mq3izy) - alprazolam 0.25 mg - alprazolam tablets are indicated for the management of anxiety disorder (a condition corresponding most closely to the apa diagnostic and statistical manual [dsm-iii-r] diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. generalized anxiety disorder is characterized by unrealistic or excessive anxiety and worry (apprehensive expectation) about two or more life circumstances, for a period of 6 months or longer, during which the person has been bothered more days than not by these concerns. at least 6 of the following 18 symptoms are often present in these patients: motor tension (trembling, twitching, or feeling shaky; muscle tension, aches, or soreness; restlessness; easy fatigability); autonomic hyperactivity (shortness of breath or smothering sensations; palpitations or accelerated heart rate; sweating, or cold clammy hands; dry mouth; dizziness or l

Amerika Serikat - Inggris - NLM (National Library of Medicine)

fresenius kabi usa, llc - ampicillin sodium (unii: jfn36l5s8k) (ampicillin - unii:7c782967rd), sulbactam sodium (unii: dkq4t82ye6) (sulbactam - unii:s4tf6i2330) - indications and usage: ampicillin and sulbactam for injection, usp is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below. skin and skin structure infections caused by beta-lactamase producing strains of staphylococcus aureus, escherichia coli,* klebsiella spp.* (including k. pneumoniae* ), proteus mirabilis,* bacteroides fragilis,* enterobacter spp.,* and acinetobacter calcoaceticus .* note: for information on use in pediatric patients see precautions, pediatric use and clinical studies sections. intra-abdominal infections caused by beta-lactamase producing strains of escherichia coli, klebsiella spp. (including k. pneumoniae* ), bacteroides spp. (including b. fr

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional llc - ropivacaine hydrochloride (unii: v910p86109) (ropivacaine - unii:7io5lya57n) - ropivacaine hydrochloride is indicated for the production of local or regional anesthesia for surgery and for acute pain management. acute pain management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor; local infiltration ropivacaine hydrochloride is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - tacrolimus (unii: wm0haq4wnm) (tacrolimus anhydrous - unii:y5l2157c4j) - tacrolimus anhydrous 0.5 mg - tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant  [see clinical studies (14.1)] , liver transplant [see clinical studies (14.2)] , and heart transplant [see clinical studies (14.3)] , and pediatric patients receiving allogeneic liver transplants [see clinical studies (14.2)]  in combination with other immunosuppressants. additional pediatric use information is approved for astellas pharma us, inc.’s prograf (tacrolimus) products. however, due to astellas pharma us, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. tacrolimus injection is contraindicated in patients with a hypersensitivity to hco-60 (polyoxyl 60 hydrogenated castor oil). hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see adverse reactions (6)] . there is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. the transplantation pregnancy registry international (tpri) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus. healthcare providers are encouraged to advise their patients to register by contacting the transplantation pregnancy registry international at 1-877-955-6877 or https://www.transplantpregnancyregistry.org/. tacrolimus can cause fetal harm when administered to a pregnant woman. data from postmarketing surveillance and tpri suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress [see human data]. advise pregnant women of the potential risk to the fetus. administration of oral tacrolimus to pregnant rabbits and rats throughout the period of organogenesis was associated with maternal toxicity/lethality, and an increased incidence of abortion, malformation and embryofetal death at clinically relevant doses (0.5 to 6.9 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). administration of oral tacrolimus to pregnant rats after organogenesis and throughout lactation produced maternal toxicity, effects on parturition, reduced pup viability and reduced pup weight at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation produced maternal toxicity/lethality, marked effects on parturition, embryofetal loss, malformations, and reduced pup viability at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died [see animal data] . the background risk of major birth defects and miscarriage in 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. risks during pregnancy are increased in organ transplant recipients. the risk of premature delivery following transplantation is increased. pre-existing hypertension and diabetes confer additional risk to the pregnancy of an organ transplant recipient. pre-gestational and gestational diabetes are associated with birth defects/congenital anomalies, hypertension, low birth weight and fetal death. cholestasis of pregnancy (cop) was reported in 7% of liver or liver-kidney (lk) transplant recipients, compared with approximately 1% of pregnancies in the general population. however, cop symptoms resolved postpartum and no long-term effects on the offspring were reported. tacrolimus may increase hyperglycemia in pregnant women with diabetes (including gestational diabetes). monitor maternal blood glucose levels regularly [see warnings and precautions (5.4)] . tacrolimus may exacerbate hypertension in pregnant women and increase pre-eclampsia. monitor and control blood pressure [see warnings and precautions (5.7, 5.8)]. renal dysfunction, transient neonatal hyperkalemia and low birth weight have been reported at the time of delivery in infants of mothers taking tacrolimus. there is an increased risk for premature delivery (< 37 weeks) following transplantation and maternal exposure to tacrolimus. there are no adequate and well controlled studies on the effects of tacrolimus in human pregnancy. safety data from the tpri and postmarketing surveillance suggest infants exposed to tacrolimus in utero have an increased risk for miscarriage, pre-term delivery (< 37 weeks), low birth weight (< 2500 g), birth defects/congenital anomalies and fetal distress. tpri reported 450 and 241 total pregnancies in kidney and liver transplant recipients exposed to tacrolimus, respectively. the tpri pregnancy outcomes are summarized in table 16. in the table below, the number of recipients exposed to tacrolimus concomitantly with mycophenolic acid (mpa) products during the preconception and first trimester periods is high (27% and 29% for renal and liver transplant recipients, respectively). because mpa products may also cause birth defects, the birth defect rate may be confounded and this should be taken into consideration when reviewing the data, particularly for birth defects. birth defects observed include cardiac malformations, craniofacial malformations, renal/urogenital disorders, skeletal abnormalities, neurological abnormalities and multiple malformations. kidney liver pregnancy outcomes * 462 253    miscarriage 24.5% 25%    live births 331 180       pre-term delivery (< 37 weeks) 49% 42%       low birth weight (< 2500 g) 42% 30%       birth defects 8% † 5% additional information reported by tpri in pregnant transplant patients receiving tacrolimus included diabetes during pregnancy in 9% of kidney recipients and 13% of liver recipients, and hypertension during pregnancy in 53% of kidney recipients and 16.2% of liver recipients. administration of oral tacrolimus to pregnant rabbits throughout organogenesis produced maternal toxicity and abortion at 0.32 mg/kg (0.5 to 1.4 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). at 1 mg/kg (1.6 to 4.3 times the recommended clinical dose range), embryofetal lethality and fetal malformations (ventricular hypoplasia, interventricular septal defect, bulbous aortic arch, stenosis of ductus arteriosus, omphalocele, gallbladder agenesis, skeletal anomalies) were observed. administration of 3.2 mg/kg oral tacrolimus (2.6 to 6.9 times the recommended clinical dose range) to pregnant rats throughout organogenesis produced maternal toxicity/lethality, embryofetal lethality and decreased fetal body weight in the offspring of c-sectioned dams; and decreased pup viability and interventricular septal defect in offspring of dams that delivered. in a peri-/postnatal development study, oral administration of tacrolimus to pregnant rats during late gestation (after organogenesis) and throughout lactation produced maternal toxicity, effects on parturition, and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range); among these pups that died early, an increased incidence of kidney hydronephrosis was observed. reduced pup weight was observed at 1.0 mg/kg (0.8 to 2.2 times the recommended clinical dose range). administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation, produced maternal toxicity/lethality, embryofetal loss and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range). interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died. effects on parturition (incomplete delivery of nonviable pups) were observed at 1 mg/kg (0.8 to 2.2 times the recommended clinical dose range) [see nonclinical toxicology (13.1)] . controlled lactation studies have not been conducted in humans; however, tacrolimus has been reported to be present in human milk. the effects of tacrolimus on the breastfed infant, or on milk production have not been assessed. tacrolimus is excreted in rat milk and in peri-/postnatal rat studies; exposure to tacrolimus during the postnatal period was associated with developmental toxicity in the offspring at clinically relevant doses [see use in specific populations (8.1)and nonclinical toxicology (13.1)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tacrolimus and any potential adverse effects on the breastfed child from tacrolimus or from the underlying maternal condition. tacrolimus can cause fetal harm when administered to pregnant women. advise female and male patients of reproductive potential to speak to their healthcare provider on family planning options including appropriate contraception prior to starting treatment with tacrolimus [see use in specific populations (8.1)and nonclinical toxicology (13.1)] . based on findings in animals, male and female fertility may be compromised by treatment with tacrolimus [see nonclinical toxicology (13.1)] . safety and effectiveness have been established in pediatric liver transplant patients. safety and efficacy in pediatric liver transplant patients less than 16 years of age are based on evidence from active controlled studies that included 56 pediatric patients, 31 of which received tacrolimus. additionally, 122 pediatric patients were studied in an uncontrolled trial of tacrolimus in living related donor liver transplantation. pediatric patients generally required higher doses of tacrolimus to maintain blood trough concentrations of tacrolimus similar to adult patients [see error! hyperlink reference not valid. , adverse reactions (6.1), clinical pharmacology (12.3)and clinical studies (14.2)] . additional pediatric use information is approved for astellas pharma us, inc.’s prograf (tacrolimus) products. however, due to astellas pharma us, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. clinical trials of tacrolimus 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. 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. the pharmacokinetics of tacrolimus in patients with renal impairment was similar to that in healthy volunteers with normal renal function. however, consideration should be given to dosing tacrolimus at the lower end of the therapeutic dosing range in patients who have received a liver or heart transplant and have pre-existing renal impairment. further reductions in dose below the targeted range may be required [see dosage and administration (2.4)and clinical pharmacology (12.3)] . the mean clearance of tacrolimus was substantially lower in patients with severe hepatic impairment (mean child-pugh score: > 10) compared to healthy volunteers with normal hepatic function. close monitoring of tacrolimus trough concentrations is warranted in patients with hepatic impairment [see clinical pharmacology (12.3)] . the use of tacrolimus in liver transplant recipients experiencing post-transplant hepatic impairment may be associated with increased risk of developing renal insufficiency related to high whole blood trough concentrations of tacrolimus. these patients should be monitored closely and dosage adjustments should be considered. some evidence suggests that lower doses should be used in these patients [see dosage and administration (2.5)and clinical pharmacology (12.3)]. african-american patients may need to be titrated to higher dosages to attain comparable trough concentrations compared to caucasian patients [see dosage and administration (2.2)and clinical pharmacology (12.3)] . african-american and hispanic patients are at increased risk for new onset diabetes after transplant. monitor blood glucose concentrations and treat appropriately [see warnings and precautions (5.4)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - atorvastatin calcium trihydrate (unii: 48a5m73z4q) (atorvastatin - unii:a0jwa85v8f) - atorvastatin 10 mg - atorvastatin calcium tablets are indicated: - to reduce the risk of: myocardial infarction (mi), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (chd) but without clinically evident chd mi and stroke in adults with type 2 diabetes mellitus with multiple risk factors for chd but without clinically evident chd non-fatal mi, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident chd - myocardial infarction (mi), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (chd) but without clinically evident chd - mi and stroke in adults with type 2 diabetes mellitus with multiple risk factors for chd but without clinically evident chd - non-fatal mi, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident chd - as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c) in: adults with primary hyperlipidemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - adults with primary hyperlipidemia. - adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to other ldl-c-lowering therapies, or alone if such treatments are unavailable, to reduce ldl-c in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia hypertriglyceridemia - primary dysbetalipoproteinemia - hypertriglyceridemia - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)] - hypersensitivity to atorvastatin or any excipients in atorvastatin calcium tablets. hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, stevens-johnson syndrome, and toxic epidermal necrolysis, have been reported [see adverse reactions (6.2)] . discontinue atorvastatin calcium tablets when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. atorvastatin calcium tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, atorvastatin calcium tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [see clinical pharmacology (12.1)]. in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with atorvastatin calcium tablets use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered atorvastatin at doses that resulted in up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (mrhd) of 80 mg, based on body surface area (mg/m 2 ). in rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development delay were observed at doses ≥ 6 times the mrhd (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 2-4% and 15-20%, respectively. a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. atorvastatin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day, respectively. atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. these doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure at the mrhd based on surface area (mg/m 2 ). in rats, the maternally toxic dose of 300 mg/kg resulted in increased post-implantation loss and decreased fetal body weight. at the maternally toxic doses of 50 and 100 mg/kg/day in rabbits, there was increased post-implantation loss, and at 100 mg/kg/day fetal body weights were decreased. in a study in pregnant rats administered 20, 100, or 225 mg/kg/day from gestation day 7 through to lactation day 20 (weaning), there was decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups of mothers dosed with 225 mg/kg/day, a dose at which maternal toxicity was observed. pup body weight was decreased through postnatal day 21 at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. pup development was delayed (rotarod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). these doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human exposure at the mrhd, based on auc. atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. there is no information about the presence of atorvastatin in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. studies in rats have shown that atorvastatin and/or its metabolites are present in the breast milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk (see data) . statins, including atorvastatin calcium tablets, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with atorvastatin calcium tablets [see use in specific populations (8.1), clinical pharmacology (12.1)] . following a single oral administration of 10 mg/kg of radioactive atorvastatin to lactating rats, the concentration of total radioactivity was determined. atorvastatin and/or its metabolites were measured in the breast milk and pup plasma at a 2:1 ratio (milk:plasma). the safety and effectiveness of atorvastatin calcium tablets as an adjunct to diet to reduce ldl-c have been established pediatric patients 10 years of age and older with hefh. use of atorvastatin calcium tablets for this indication is based on a double-blind, placebo-controlled clinical trial in 187 pediatric patients 10 years of age and older with hefh. in this limited controlled trial, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of atorvastatin calcium tablets as an adjunct to other ldl-c-lowering therapies to reduce ldl-c have been established pediatric patients 10 years of age and older with hofh. use of atorvastatin calcium tablets for this indication is based on a trial without a concurrent control group in 8 pediatric patients 10 years of age and older with hofh [see clinical studies (14)] . the safety and effectiveness of atorvastatin calcium tablets have not been established in pediatric patients younger than 10 years of age with hefh or hofh, or in pediatric patients with other types of hyperlipidemia (other than hefh or hofh). of the total number of atorvastatin-treated patients in clinical trials, 15,813 (40%) were ≥ 65 years old and 2,800 (7%) were ≥ 75 years old. no overall differences in safety or effectiveness were observed between these patients and younger patients. advanced age (≥ 65 years) is a risk factor for atorvastatin-associated myopathy and rhabdomyolysis. dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. monitor geriatric patients receiving atorvastatin calcium tablets for the increased risk of myopathy [see warnings and precautions (5.1)and clinical pharmacology (12.3)] . renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. renal impairment does not affect the plasma concentrations of atorvastatin calcium tablets, therefore there is no dosage adjustment in patients with renal impairment [see warnings and precautions (5.1)and clinical pharmacology (12.3)]. in patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin calcium tablets are markedly increased. cmax and auc are each 4-fold greater in patients with childs-pugh a disease. cmax and auc are approximately 16-fold and 11-fold increased, respectively, in patients with childs-pugh b disease. atorvastatin calcium tablets are contraindicated in patients with acute liver failure or decompensated cirrhosis [see   contraindications (4)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

west-ward pharmaceticals corp. - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine 150 mg - oxcarbazepine tablets are indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [see warnings and precautions (5.2, 5.3)]. pregnancy exposure registry: there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine, during pregnancy. encourage women who are taking oxcarbazepine 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: there are no adequate data on the developmental risks associated with the use of oxcarbaze

Amerika Serikat - Inggris - NLM (National Library of Medicine)

mylan institutional inc. - glyburide (unii: sx6k58tvwc) (glyburide - unii:sx6k58tvwc) - glyburide 2.5 mg - glyburide tablets usp are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. glyburide tablets are contraindicated in patients with: - known hypersensitivity or allergy to the drug. - diabetic ketoacidosis, with or without coma. this condition should be treated with insulin. - type i diabetes mellitus. - concomitant administration of bosentan.

Amerika Serikat - Inggris - NLM (National Library of Medicine)

purdue pharma lp - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 80 mg - oxycontin is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate in: - adults; and - opioid-tolerant pediatric patients 11 years of age and older who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve oxycontin for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - oxycontin is not indicated as an as-needed (prn) analgesic. oxycontin is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.8)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.13)] - hypersensitivity (e.g., anaphylaxis) to oxycodone [see adverse reactions (6.2)] risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . there are no available data with oxycontin in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, there was no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the period of organogenesis, at doses 1.3 to 40 times the adult human dose of 60 mg/day, respectively. in a pre- and postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup body weight during lactation and the early post-weaning period at the dose equivalent to an adult dose of 60 mg/day. in several published studies, treatment of pregnant rats with oxycodone hydrochloride at clinically relevant doses and below resulted in neurobehavioral effects in offspring [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the 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 fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. oxycontin is not recommended for use in women immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including oxycontin, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data pregnant rats were treated with 0.5, 2, 4, and 8 mg/kg oxycodone hydrochloride (0.08, 0.3, 0.7, and 1.3 times the human daily dose of 60 mg/day, respectively based on a mg/m2 basis) during the period of organogenesis. oxycodone did not cause adverse effects to the fetus at exposures up to 1.3 times the human dose of 60 mg/day. the high dose produced maternal toxicity characterized by excessive gnawing on forelimbs and decreased body weight gain. pregnant rabbits were treated with 1, 5, 25, and 125 mg/kg oxycodone hydrochloride (0.3, 2, 8, and 40 times the human daily dose of 60 mg/day, respectively, based on a mg/m2 basis) during the period of organogenesis. oxycodone did not cause adverse effects to the fetus at exposures up to 40 times the human dose of 60 mg/day. the 25 mg/kg and 125 mg/kg doses high doses produced maternal toxicity characterized by decreased food consumption and body weight gain. pregnant rats were treated with 0.5, 2, and 6 mg/kg oxycodone hydrochloride (0.08, 0.32, and 1 times the human daily dose of 60 mg/kg, respective, based on a mg/m2 basis, during the period of organogenesis through lactation. decreased body weight was found during lactation and the early post-weaning phase in pups nursed by mothers given the highest dose used (6 mg/kg/day, equivalent to an adult human dose of 60 mg/day, on a mg/m2 basis). however, body weight of these pups recovered. in published studies, offspring of pregnant rats administered oxycodone hydrochloride during gestation have been reported to exhibit neurobehavioral effects including altered stress responses and increased anxiety-like behavior (2 mg/kg/day iv from gestation day 8 to 21 and postnatal day 1, 3, and 5; 0.3 times an adult human oral dose of 60 mg/day on a mg/m2 basis), and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human oral dose of 60 mg/day on a mg/m2 basis). oxycodone is present in breast milk. published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. the lactation studies did not assess breastfed infants for potential adverse reactions. lactation studies have not been conducted with extended–release oxycodone, including oxycontin, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with oxycontin. clinical considerations monitor infants exposed to oxycontin through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)] . the safety and efficacy of oxycontin have been established in pediatric patients ages 11 to 16 years. use of oxycontin is supported by evidence from adequate and well-controlled trials with oxycontin in adults as well as an open-label study in pediatric patients ages 6 to 16 years. however, there were insufficient numbers of patients less than 11 years of age enrolled in this study to establish the safety of the product in this age group. the safety of oxycontin in pediatric patients was evaluated in 155 patients previously receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent on the two days immediately preceding dosing with oxycontin. patients were started on a total daily dose ranging between 20 mg and 100 mg depending on prior opioid dose. the most frequent adverse events observed in pediatric patients were vomiting, nausea, headache, pyrexia, and constipation [see dosage and administration (2.5), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14)] . in controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see clinical pharmacology (12.3)] . of the total number of subjects (445) in clinical studies of oxycodone hydrochloride controlled-release tablets, 148 (33.3%) were age 65 and older (including those age 75 and older) while 40 (9.0%) were age 75 and older. in clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received oxycodone hydrochloride controlled-release tablets. thus, the usual doses and dosing intervals may be appropriate for elderly patients. however, a dosage reduction in debilitated, non-opioid-tolerant patients is recommended [see dosage and administration (2.8)] . respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who are not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of oxycontin slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression. [see warnings and precautions (5.8)] . oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. a study of oxycontin in patients with hepatic impairment demonstrated greater plasma concentrations than those seen at equivalent doses in persons with normal hepatic function [see clinical pharmacology (12.3)] . therefore, a dosage reduction is recommended for these patients [see dosage and administration (2.9)]. regularly evaluate closely for signs of respiratory depression, sedation, and hypotension. in patients with renal impairment, as evidenced by decreased creatinine clearance (<60 ml/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function [see clinical pharmacology (12.3)] . follow a conservative approach to dose initiation and adjust according to the clinical situation. in pharmacokinetic studies with oxycontin, opioid-naïve females demonstrate up to 25% higher average plasma concentrations and greater frequency of typical opioid adverse events than males, even after adjustment for body weight. the clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages, and there was no male/female difference detected for efficacy or adverse events in clinical trials. oxycontin contains oxycodone, a schedule ii controlled substance. oxycontin contains oxycodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care 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 oxycontin 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 oxycontin with alcohol and/or 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 oxycontin abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use oxycontin 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. oxycontin, 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 oxycontin abuse of oxycontin poses a risk of overdose and death. this risk is increased with concurrent abuse of oxycontin with alcohol and/or other cns depressants [see warnings and precautions (5.1, 5.3), drug interactions (7)] . taking cut, broken, chewed, crushed, or dissolved oxycontin enhances drug release and increases the risk of overdose and death. oxycontin is approved for oral use only. with parenteral abuse, the inactive ingredients in oxycontin can be expected to result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, valvular heart injury, embolism, and death. cases of thrombotic microangiopathy (a condition characterized clinically by thrombocytopenia, microangiopathic hemolytic anemia) associated with parenteral abuse have been reported. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. abuse deterrence studies oxycontin is formulated with inactive ingredients intended to make the tablet more difficult to manipulate for misuse and abuse. for the purposes of describing the results of studies of the abuse-deterrent characteristics of oxycontin resulting from a change in formulation, in this section, the original formulation of oxycontin, which is no longer marketed, will be referred to as “original oxycontin” and the reformulated, currently marketed product will be referred to as “oxycontin". in vitro testing in vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation. results support that, relative to original oxycontin, there is an increase in the ability of oxycontin to resist crushing, breaking, and dissolution using a variety of tools and solvents. the results of these studies also support this finding for oxycontin relative to an immediate-release oxycodone. when subjected to an aqueous environment, oxycontin gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a needle. clinical studies in a randomized, double-blind, placebo-controlled 5-period crossover pharmacodynamic study, 30 recreational opioid users with a history of intranasal drug abuse received intranasally administered active and placebo drug treatments. the five treatment arms were finely crushed oxycontin 30 mg tablets, coarsely crushed oxycontin 30 mg tablets, finely crushed original oxycontin 30 mg tablets, powdered oxycodone hcl 30 mg, and placebo. data for finely crushed oxycontin, finely crushed original oxycontin, and powdered oxycodone hcl are described below. drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking and 100 represents maximum liking. response to whether the subject would take the study drug again was also measured on a bipolar scale of 0 to 100 where 50 represents a neutral response, 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”). twenty-seven of the subjects completed the study. incomplete dosing due to granules falling from the subjects’ nostrils occurred in 34% (n = 10) of subjects with finely crushed oxycontin, compared with 7% (n = 2) of subjects with finely crushed original oxycontin and no subjects with powdered oxycodone hcl. the intranasal administration of finely crushed oxycontin was associated with a numerically lower mean and median drug liking score and a lower mean and median score for take drug again, compared to finely crushed original oxycontin or powdered oxycodone hcl as summarized in table 5. figure 1 demonstrates a comparison of drug liking for finely crushed oxycontin compared to powdered oxycodone hcl in subjects who received both treatments.  the y-axis represents the percent of subjects attaining a percent reduction in drug liking for oxycontin vs. oxycodone hcl powder greater than or equal to the value on the x-axis. approximately 44% (n = 12) had no reduction in liking with oxycontin relative to oxycodone hcl. approximately 56% (n = 15) of subjects had some reduction in drug liking with oxycontin relative to oxycodone hcl. thirty-three percent (n = 9) of subjects had a reduction of at least 30% in drug liking with oxycontin compared to oxycodone hcl, and approximately 22% (n = 6) of subjects had a reduction of at least 50% in drug liking with oxycontin compared to oxycodone hcl. figure 1: percent reduction profiles for emax of drug liking vas for oxycontin vs. oxycodone hcl, n=27 following intranasal administration the results of a similar analysis of drug liking for finely crushed oxycontin relative to finely crushed original oxycontin were comparable to the results of finely crushed oxycontin relative to powdered oxycodone hcl. approximately 43% (n = 12) of subjects had no reduction in liking with oxycontin relative to original oxycontin. approximately 57% (n = 16) of subjects had some reduction in drug liking, 36% (n = 10) of subjects had a reduction of at least 30% in drug liking, and approximately 29% (n = 8) of subjects had a reduction of at least 50% in drug liking with oxycontin compared to original oxycontin. summary the in vitro data demonstrate that oxycontin has physicochemical properties expected to make abuse via injection difficult. the data from the clinical study, along with support from the in vitro data, also indicate that oxycontin has physicochemical properties that are expected to reduce abuse via the intranasal route. however, abuse of oxycontin by these routes, as well as by the oral route, is still possible. additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of oxycontin on the abuse liability of the drug. accordingly, this section may be updated in the future as appropriate. oxycontin contains oxycodone, an opioid agonist and schedule ii controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. oxycontin can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1), drug abuse and dependence (9.1)]. 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 oxycontin in a patient physically dependent on opioids. rapid tapering of oxycontin 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 oxycontin, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycontin 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 (2.10), warnings and precautions (5.15)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)].