Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

actavis pharma, inc. - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine 15 mg - mirtazapine tablets, usp are indicated for the treatment of major depressive disorder. the efficacy of mirtazapine in the treatment of major depressive disorder was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the diagnostic and statistical manual of mental disorders - 3rd edition (dsm-iii) category of major depressive disorder (see clinical pharmacology ). a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation. the effectiveness of mirtazapine in hospitalized depress

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

gemini pharmaceuticals, inc. dba plus pharma - docusate sodium (unii: f05q2t2ja0) (docusate - unii:m7p27195ag), sennosides (unii: 3fyp5m0ijx) (sennosides - unii:3fyp5m0ijx) - docusate sodium 50 mg - purposes stool softener laxative uses - relieves occasional constipation (irregularity) - generally produces a bowel movement in 6-12 hours

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

agri-services llc - iodine (unii: 9679tc07x4) (iodine - unii:9679tc07x4) - iodine 11.2 g in 1 l

Аустралија - Енглески - Department of Health (Therapeutic Goods Administration)

arrotex pharmaceuticals pty ltd - lisinopril dihydrate, quantity: 10.89 mg (equivalent: lisinopril, qty 10 mg) - tablet, uncoated - excipient ingredients: calcium hydrogen phosphate dihydrate; mannitol; maize starch; pregelatinised maize starch; magnesium stearate; colloidal anhydrous silica - hypertension: treatment of hypertension. lisinopril may be used alone or concomitantly with other classes of antihypertensive agents. sufficient data have not been provided to support the use of lisinopril in severe hypertension or renovascular hypertension. congestive heart failure: treatment of heart failure. in such patients, it is recommended that lisinopril be administered together with a diuretic. acute myocardial infarction: treatment of acute myocardial infarction in haemodynamically stable patients, defined as patients who are not in cardiogenic shock and who have a systolic blood pressure greater than 100 mmhg. lisinopril may be initiated within 24 hours of an acute myocardial infarction.

Аустралија - Енглески - Department of Health (Therapeutic Goods Administration)

arrotex pharmaceuticals pty ltd - rosuvastatin calcium, quantity: 10.4 mg - tablet, film coated - excipient ingredients: colloidal anhydrous silica; magnesium stearate; microcrystalline cellulose; lactose monohydrate; crospovidone; titanium dioxide; hypromellose; sunset yellow fcf aluminium lake; triacetin; allura red ac aluminium lake; indigo carmine aluminium lake; iron oxide red - crosuva is indicated as an adjunct to diet when the response to diet and exercise is inadequate. prevention of cardiovascular events: crosuva is indicated for prevention of major cardiovascular events in men greater than or equal to 50 years old and women greater than or equal to 60 years old with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease (hypertension, low hdl-c, smoking, or a family history of premature coronary heart disease). crosuva is indicated to: reduce the risk of nonfatal myocardial infarction; reduce the risk of nonfatal stroke; reduce the risk of coronary artery revascularisation procedures. in patients with hypercholesterolaemia: crosuva is indicated for the treatment of hypercholesterolaemia (including familial hypercholesterolaemia). prior to initiating therapy with crosuva, secondary causes of hypercholesterolaemia (e.g. poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver disease, other drug therapy, alcoholism) should be identified and treated.

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

par pharmaceutical, inc. - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - fluoxetine 60 mg - fluoxetine tablets are indicated for the treatment of: - major depressive disorder (mdd). the efficacy of fluoxetine tablets in mdd was established in one 5-week trial, three 6-week trials, and one maintenance study in adults. the efficacy of fluoxetine tablets was also established in two 8- to 9-week trials in pediatric patients 8 to 18 years of age [see clinical studies (14.1)]. - obsessions and compulsions in patients with obsessive compulsive disorder (ocd). the efficacy of fluoxetine tablets in ocd was demonstrated in two 13-week trials in adults and one 13-week trial in pediatric patients 7 to 17 years of age [see clinical studies (14.2)]. - binge-eating and vomiting behaviors in patients with moderate to severe bulimia nervosa. the efficacy of fluoxetine tablets in bulimia nervosa was demonstrated in two 8-week trials and one 16-week trial in adults [see clinical studies (14.3)]. - panic disorder, with or without agoraphobia. the efficacy of fluoxetine tablets in panic disorder was demonstrated in two 12-week trials in adults [see clinical studies (14.4)]. the use of maois intended to treat psychiatric disorders with fluoxetine tablets or within 5 weeks of stopping treatment with fluoxetine tablets is contraindicated because of an increased risk of serotonin syndrome. the use of fluoxetine tablets within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.6) and warnings and precautions (5.2)]. starting fluoxetine tablets in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.7) and warnings and precautions (5.2)]. the use of fluoxetine tablets is contraindicated with the following: - pimozide [see warnings and precautions (5.11) and drug interactions (7.6, 7.7)] -   thioridazine [see warnings and precautions (5.11) and drug interactions (7.6, 7.7)] pimozide and thioridazine prolong the qt interval. fluoxetine tablets can increase the levels of pimozide and thioridazine through inhibition of cyp2d6. fluoxetine tablets can also prolong the qt interval. - known hypersensitivity to fluoxetine tablets: do not use this product in patients with known hypersensitivity to fluoxetine tablets due to risk of anaphylactoid reactions, including bronchospasm, angioedema, laryngospasm, and urticaria [see warnings and precautions (5.3)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.7) and clinical considerations]. available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage. some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship [see data]. there are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including fluoxetine tablets, during pregnancy (see clinical considerations). in rats and rabbits treated with fluoxetine during the period of organogenesis, there was no evidence of developmental effects at doses up to 1.6 and 3.9 times, respectively, the maximum recommended human dose (mrhd) of 60 mg on a mg/m2 given to adolescents on a mg/m2 basis. however, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 times (during gestation and lactation) the mrhd given to adolescents on a mg/m2 basis. 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 us 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 women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of fluoxetine tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)]. fetal/neonatal adverse reactions neonates exposed to fluoxetine tablets and other ssris or snris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of ssris and snris or possibly a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.2)]. data human data it has been shown that ssris (including fluoxetine) can cross the placenta. published epidemiological studies of pregnant women exposed to fluoxetine have not established an increased risk of major birth defects, miscarriage, and other adverse developmental outcomes. several publications reported an increased incidence of cardiovascular malformations in children with in utero exposure to fluoxetine. however, these studies results do not establish a causal relationship. methodologic limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders and confirmatory studies. however, these studies cannot definitely establish or exclude any drug-associated risk during pregnancy. exposure to ssris, particularly later in pregnancy, may have an increased risk for pphn. pphn occurs in 1 to 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. animal data in embryofetal development studies in rats and rabbits, there was no evidence of malformations or developmental variations following administration of fluoxetine at doses up to 12.5 and 15 mg/kg/day, respectively (1.6 and 3.9 times, respectively, the mrhd of 60 mg given to adolescents on a mg/m2 basis) throughout organogenesis. however, in rat reproduction studies, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths during the first 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the mrhd given to adolescents on a mg/m2 basis) during gestation or 7.5 mg/kg/day (0.97 times the mrhd given to adolescents on a mg/m2 basis) during gestation and lactation. there was no evidence of developmental neurotoxicity in the surviving offspring of rats treated with 12 mg/kg/day during gestation. the no-effect dose for rat pup mortality was 5 mg/kg/day (0.65 times the mrhd given to adolescents on a mg/m2 basis). risk summary data from published literature report the presence of fluoxetine and norfluoxetine in human milk (see data) . there are reports of agitation, irritability, poor feeding, and poor weight gain in infants exposed to fluoxetine through breast milk (see clinical considerations) . there are no data on the effect of fluoxetine or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluoxetine tablets and any potential adverse effects on the breastfed child from fluoxetine tablets or the underlying maternal condition. clinical considerations infants exposed to fluoxetine tablets should be monitored for agitation, irritability, poor feeding, and poor weight gain. data a study of 19 nursing mothers on fluoxetine with daily doses of 10 to 60 mg showed that fluoxetine was detectable in 30% of nursing infant sera (range: 1 to 84 ng/ml) whereas norfluoxetine was found in 85% (range: <1 to 265 ng/ml). use of fluoxetine in children —the efficacy of fluoxetine for the treatment of mdd was demonstrated in two 8- to 9-week placebo-controlled clinical trials with 315 pediatric outpatients ages 8 to ≤18 [see clinical studies (14.1)]. the efficacy of fluoxetine for the treatment of ocd was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to < 18 [see clinical studies (14.2)]. the safety and effectiveness in pediatric patients < 8 years of age in mdd and < 7 years of age in ocd have not been established. fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to ≤18) with mdd or ocd [see clinical pharmacology (12.3)]. the acute adverse reaction profiles observed in the 3 studies (n = 418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. the longer-term adverse reaction profile observed in the 19-week mdd study (n = 219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine [see adverse reactions (6.1)]. manic reaction, including mania and hypomania, was reported in 6 (1 mania, 5 hypomania) out of 228 (2.6%) fluoxetine-treated patients and in 0 out of 190 (0%) placebo-treated patients. mania/hypomania led to the discontinuation of 4 (1.8%) fluoxetine-treated patients from the acute phases of the 3 studies combined. consequently, regular monitoring for the occurrence of mania/hypomania is recommended. as with other ssris, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. after 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1.1 cm less in height and 1.1 kg less in weight than subjects treated with placebo. in addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. the safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. in particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development, and maturation of children and adolescent patients. therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine [see warnings and precautions (5.6)]. fluoxetine is approved for use in pediatric patients with mdd and ocd [see boxed warning and warnings and precautions (5.1)]. anyone considering the use of fluoxetine in a child or adolescent must balance the potential risks with the clinical need. junvenile  animal toxicity data —significant toxicity on muscle tissue, neurobehavior, reproductive organs, and bone development has been observed following exposure of juvenile rats to fluoxetine from weaning through maturity. oral administration of fluoxetine to rats from weaning postnatal day 21 through adulthood day 90 at 3, 10, or 30 mg/kg/day was associated with testicular degeneration and necrosis, epididymal vacuolation, and hypospermia (at 30 mg/kg/day corresponding to plasma exposures [auc] approximately 5 to 10 times the average auc in pediatric patients at the mrhd of 20 mg/day); increased serum levels of creatine kinase (at auc as low as 1 to 2 times the average auc in pediatric patients at the mrhd of 20 mg/day); skeletal muscle degeneration and necrosis; decreased femur length/growth; and body weight gain (at auc 5 to 10 times the average auc in pediatric patients at the mrhd of 20 mg/day). the high dose of 30 mg/kg/day exceeded a maximum tolerated dose. when animals were evaluated after a drug-free period (up to 11 weeks after cessation of dosing), fluoxetine was associated with neurobehavioral abnormalities (decreased reactivity at auc as low as approximately 0.1 to 0.2 times the average auc in pediatric patients at the mrhd and learning deficit at the high dose) and reproductive functional impairment (decreased mating at all doses and impaired fertility at the high dose). in addition, the testicular and epididymal microscopic lesions and decreased sperm concentrations found in the high dose group were also observed, indicating that the drug effects on reproductive organs are irreversible. the reversibility of fluoxetine-induced muscle damage was not assessed. these fluoxetine toxicities in juvenile rats have not been observed in adult animals. plasma exposures (auc) to fluoxetine in juvenile rats receiving 3, 10, or 30 mg/kg/day doses in this study are approximately 0.1 to 0.2, 1 to 2, and 5 to 10 times, respectively, the average exposure in pediatric patients receiving the mrhd of 20 mg/day. rat exposures to the major metabolite, norfluoxetine, were approximately 0.3 to 0.8, 1 to 8, and 3 to 20 times, respectively, the pediatric exposure at the mrhd. a specific effect on bone development was reported in juvenile mice administered fluoxetine by the intraperitoneal route to 4-week-old mice for 4 weeks at doses 0.5 and 2 times the oral mrhd of 20 mg/day on a mg/m2 basis. there was a decrease in bone mineralization and density at both doses, but the overall growth (body weight gain or femur length) was not affected. u.s. fluoxetine clinical trials included 687 patients ≥65 years of age and 93 patients ≥75 years of age. the efficacy in geriatric patients has been established [see clinical studies (14.1)]. for pharmacokinetic information in geriatric patients, [see clinical pharmacology (12.3)]. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. snris and ssris, including fluoxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.9)]. in subjects with cirrhosis of the liver, the clearances of fluoxetine and its active metabolite, norfluoxetine, were decreased, thus increasing the elimination half-lives of these substances. a lower or less frequent dose of fluoxetine should be used in patients with cirrhosis. caution is advised when using fluoxetine in patients with diseases or conditions that could affect its metabolism [see dosage and administration (2.5) and clinical pharmacology (12.3)]. fluoxetine has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. while the premarketing clinical experience with fluoxetine did not reveal any tendency for a withdrawal syndrome or 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. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of fluoxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine is indicated for the treatment of schizophrenia. the efficacy of quetiapine in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (13 to 17 years). the effectiveness of quetiapine for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [see clinical studies ( 14.1)]. quetiapine is indicated for the acute treatment of manic episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10 to 17 years) [see clinical studies ( 14.2)]. quetiapine is indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. efficacy was established in two 8-week monotherapy trials in adult pa

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

pharmaceutical associates, inc. - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram oral solution, usp is indicated for the treatment of depression. the efficacy of citalopram oral solution, usp in the treatment of depression was established in 4-6 week, controlled trials of outpatients whose diagnosis corresponded most closely to the dsm-iii and dsm-iii-r category of major depressive disorder (see clinical pharmacology ). a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. the antidepressant action of citalopram oral solution, usp in hospitalized depressed patients has

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

collegium pharmaceutical, inc. - tapentadol hydrochloride (unii: 71204kii53) (tapentadol - unii:h8a007m585) - nucynta (tapentadol) tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults and pediatric patients aged 6 years and older with a body weight of at least 40kg. limitations of use because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dose or duration [see warnings and precautions (5.1)] , reserve nucynta tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: - have not been tolerated or are not expected to be tolerated, - have not provided adequate analgesia or are not expected to provide adequate analgesia nucynta tablets 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. nucynta tablets are 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 suspected paralytic ileus [see warnings and precautions (5.12)] - hypersensitivity to tapentadol (e.g., anaphylaxis, angioedema) or to any other ingredients of the product [see adverse reactions (6.2)] - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see drug interactions (7)] 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)] . available data with nucynta tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. there are risks to the mother and infant associated with use of nucynta tablets for an extended period of time during pregnancy (see clinical considerations). in animal reproduction studies, embryofetal mortality and structural malformations were observed with subcutaneous administration of tapentadol during organogenesis to rabbits and delays in skeletal maturation were observed in rats at exposures equivalent to and less than the maximum recommended human dose (mrhd), respectively. when administered to pregnant rats during organogenesis and through lactation, increased pup mortality was noted following oral tapentadol exposures to doses equivalent to the mrhd [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 reaction. 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. 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. nucynta tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including nucynta tablets, 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 dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data tapentadol hcl was evaluated for teratogenic effects in pregnant rats and rabbits following subcutaneous exposure during organogenesis. when tapentadol was administered twice daily by the subcutaneous route in rats at dose levels of 10, 20, or 40 mg/kg/day [producing up to 1 times the plasma exposure at the maximum recommended human dose (mrhd) of 700 mg/day based on an area under the time-curve (auc) comparison], no teratogenic effects were observed. evidence of embryofetal toxicity included transient delays in skeletal maturation (i.e. reduced ossification) at the 40 mg/kg/day dose which was associated with significant maternal toxicity. administration of tapentadol hcl in rabbits at doses of 4, 10, or 24 mg/kg/day by subcutaneous injection [producing 0.2, 0.6, and 1.85 times the plasma exposure at the mrhd based on an auc comparison] revealed embryofetal toxicity at doses ≥10 mg/kg/day. findings included reduced fetal viability, skeletal delays and other variations. in addition, there were multiple malformations including gastroschisis/thoracogastroschisis, amelia/phocomelia, and cleft palate at doses ≥10 mg/kg/day and above, and ablepharia, encephalopathy, and spina bifida at the high dose of 24 mg/kg/day. embryofetal toxicity, including malformations, may be secondary to the significant maternal toxicity observed in the study. in a study of pre- and postnatal development in rats, oral administration of tapentadol at doses of 20, 50, 150, or 300 mg/kg/day to pregnant and lactating rats during the late gestation and early postnatal period [resulting in up to 1.7 times the plasma exposure at the mrhd on an auc basis] did not influence physical or reflex development, the outcome of neurobehavioral tests or reproductive parameters. treatment-related developmental delay was observed, including incomplete ossification, and significant reductions in pup body weights and body weight gains at doses associated with maternal toxicity (150 mg/kg/day and above). at maternal tapentadol doses ≥150 mg/kg/day, a dose-related increase in pup mortality was observed through postnatal day 4. risk summary there are no data on the presence of tapentadol in human milk, the effects on the breastfed infant, or the effects on milk production. tapentadol 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. infants exposed to nucynta tablets through breast milk should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for nucynta tablets and any potential adverse effects on the breastfed infant from nucynta tablets or from the underlying maternal condition. 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)]. the safety and effectiveness of nucynta (tapentadol) tablets in pediatric patients ages 6 years and older who weigh at least 40 kg have been established. use of nucynta (tapentadol) tablets in pediatric patients ages 6 years and older who weigh at least 40 kg is based on one randomized, double-blind, placebo-controlled, multiple-dose efficacy and safety study of nucynta (tapentadol) oral solution in 175 pediatric patients from birth to 17 years of age who had undergone surgery that would reliably produce moderate to severe pain and supported by pharmacokinetic and safety data from three open-label, single-dose studies of nucynta (tapentadol) oral solution in 129 patients from birth to 17 years of age with moderate to severe acute pain from a surgical procedure [see clinical studies (14.2)] . the safety and effectiveness of nucynta (tapentadol) tablets in pediatric patients less than 6 years of age have not been established. in pediatric patients less than 6 years of age, nucynta (tapentadol) oral solution did not demonstrate efficacy compared to placebo when evaluated in one randomized, double-blind, placebo-controlled, multiple-dose study in 175 pediatric patients from birth to 17 years of age who had undergone surgery that would reliably produce moderate to severe pain [see clinical studies (14.2)] . the safety and effectiveness of nucynta (tapentadol) tablets in pediatric patients who weigh less than 40 kg have not been established because the recommended dosage cannot be achieved with available tablet strengths. consider use of another nucynta product, such as nucynta (tapentadol) oral solution, in patients who cannot swallow oral tablets or who weigh less than 40 kg [see dosage and administration (2.3)] . nucynta (tapentadol) tablets have not been studied in pediatric patients with hepatic or renal impairment; therefore, use in these populations is not recommended [see dosage and administration (2.4)] . of the total number of patients in phase 2/3 double-blind, multiple-dose clinical studies of nucynta tablets, 19% were 65 and over, while 5% were 75 and over. no overall differences in effectiveness were observed between these patients and younger patients. the rate of constipation was higher in subjects greater than or equal to 65 years than those less than 65 years (12% vs. 7%). elderly patients (aged 65 years or older) may have increased sensitivity to tapentadol. in general, use caution when selecting a dosage for an elderly patient, 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. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of nucynta tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.2)] . tapentadol 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. administration of tapentadol resulted in higher exposures and serum levels of tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function [see clinical pharmacology (12.3)] . use of nucynta tablets are not recommended in patients with severe hepatic impairment (child-pugh score 10 to 15) [see warnings and precautions (5.17)] . the dose of nucynta tablets should be reduced in patients with moderate hepatic impairment (child-pugh score 7 to 9) [see dosage and administration (2.5)]. no dosage adjustment is recommended in patients with mild hepatic impairment (child-pugh score 5 to 6) [see warnings and precautions (5.17), clinical pharmacology (12.3)]. use of nucynta tablets in patients with severe renal impairment (creatinine clearance less than 30 ml/minute) is not recommended. no dosage adjustment is recommended in patients with mild or moderate renal impairment (creatinine clearance 30-90 ml/minute) [see warnings and precautions (5.18), clinical pharmacology (12.1)] . nucynta tablets contain tapentadol, a schedule ii controlled substance. nucynta tablets contain tapentadol, 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 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 nucynta tablets increase 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 nucynta tablets 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 nucynta tablet abuse include those with a history of prolonged use of any opioid, including products containing tapentadol, those with a history of drug or alcohol abuse, or those who use nucynta tablets 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. nucynta tablets, 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 nucynta tablets abuse of nucynta tablets pose a risk of overdose and death. the risk is increased with concurrent use of nucynta tablets with alcohol and/or other central nervous system depressants. nucynta tablets are approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. 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 nucynta tablets in a patient physically dependent on opioids. rapid tapering of nucynta tablets 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 nucynta tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of nucynta tablets 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 (2.7), and warnings and precautions (5.13)]. 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)].

Сједињене Америчке Државе - Енглески - NLM (National Library of Medicine)

caplin steriles limited - glycopyrrolate (unii: v92so9wp2i) (glycopyrronium - unii:a14fb57v1d) - in anesthesia   glycopyrrolate injection, usp is indicated for use as a preoperative antimuscarinic to reduce salivary, tracheobronchial, and pharyngeal secretions; to reduce the volume and free acidity of gastric secretions; and to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation. when indicated, glycopyrrolate injection, usp may be used intraoperatively to counteract surgically or drug‑induced or vagal reflexes associated arrhythmias. glycopyrrolate protects against the peripheral muscarinic effects (e.g., bradycardia and excessive secretions) of cholinergic agents such as neostigmine and pyridostigmine given to reverse the neuromuscular blockade due to non-depolarizing muscle relaxants. in peptic ulcer   for use in adults as adjunctive therapy for the treatment of peptic ulcer when rapid anticholinergic effect is desired or when oral medication is not tolerated. known hypersensitivity to glycopyrrolate or any of its inactive ingredients. in addition, in the management o