ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - in adults to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . - in pediatric patients aged 3 years and older with idiopathic or congenital pah to improve pulmonary vascular resistance (pvr), which is expected to result in an improvement in exercise ability. use of bosentan is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . coadministration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of bosentan and cyclosporine a is contraindicated [see cytochrome p450  drug interactions (7.1)] . an increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. therefore coadministration of glyburide and bosentan is contraindicated [see cytochrome p450  drug interactions (7.1)] . bosentan is contraindicated in patients who are hypersensitive to bosentan or any component of the product. observed reactions include drug reaction with eosinophilia and systemic symptoms (dress), anaphylaxis, rash, and angioedema [see adverse reactions (6.2), description (11)] . risk summary based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see contraindications (4.1)] . there are limited data on bosentan use in pregnant women. in animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (mrhd) on a mg/m2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see animal data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data bosentan was teratogenic in rats given oral doses two times the mrhd (on a mg/m2 basis). in an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels. bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the mrhd (on a mg/m2 basis). although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. the similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs. risk summary data from a case report describe the presence of bosentan in human milk. there is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan on milk production. because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating bosentan, monthly during treatment and one month after stopping treatment with bosentan. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus. contraception drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives. based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using bosentan and should not be used as a patient’s only contraceptive method [see drug interactions (7.2)] . females of reproductive potential using bosentan must use two acceptable methods of contraception during treatment and for 1 month after treatment with bosentan. patients may choose one highly effective form of contraception (intrauterine devices (iud) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see boxed warning] . infertility males decreased sperm counts have been observed in patients receiving bosentan. based on these findings and findings in animals, bosentan may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.6), adverse reactions (6.1), nonclinical toxicology (13.1)] . the efficacy of bosentan in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with bosentan. in this study, cardiopulmonary hemodynamic improvements were similar to those seen in adults treated with bosentan [see pulmonary arterial hypertension (14.1)] . safety in pediatric patients is supported by data from 100 pediatric patients treated with bosentan for a median of 17 months [see clinical studies experience (6.1), pulmonary arterial hypertension (14.1)] . juvenile animal toxicity data in a juvenile rat toxicity study, rats were treated from day 4 postpartum to adulthood (day 69 postpartum). decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning. no effect on testis histology or sperm morphology and function was seen. the noael was 4 times (at day 4 postpartum) and 2 times (day 69 postpartum) the human therapeutic exposure, respectively. no effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with pah. clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. because there is in vitro and in vivo evidence that the main route of excretion of bosentan is biliary, liver impairment could be expected to increase exposure (cmax and auc) of bosentan. the pharmacokinetics of bosentan have not been evaluated in patients with severe liver impairment (child-pugh class c). in patients with moderate hepatic impairment (child-pugh class b), the systemic exposures to bosentan and its active metabolite increased significantly. bosentan should generally be avoided in patients with moderate or severe liver impairment. pharmacokinetics of bosentan were not altered in patients with mild impairment of hepatic function (child-pugh class a) [see dosage and administration (2.6), warnings and precautions (5.1), pharmacokinetics (12.3)] . the effect of renal impairment on the pharmacokinetics of bosentan is small and does not require dosing adjustment [see pharmacokinetics (12.3)] .

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - oxazepam (unii: 6gow6dwn2a) (oxazepam - unii:6gow6dwn2a) - oxazepam 10 mg - oxazepam capsules are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. anxiety associated with depression is also responsive to oxazepam therapy. this product has been found particularly useful in the management of anxiety, tension, agitation and irritability in older patients. alcoholics with acute tremulousness, inebriation, or with anxiety associated with alcohol withdrawal are responsive to therapy. the effectiveness of oxazepam 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. history of previous hypersensitivity reaction to oxazepam. oxazepam is not indicated in psychoses. controlled substance oxazepam is a schedule iv controlled substance. abuse oxazepam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, nontherapeutic use of a drug, even once, for its desirable psychological or physiological effects. 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. 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. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see warnings: abuse, misuse, and addiction ] . the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). dependence physical dependence oxazepam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of 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. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see warnings: dependence and withdrawal reactions ] . to reduce the risk of withdrawal reactions, use a gradual taper to discontinue oxazepam or reduce the dosage [see dosage and administration: discontinuation or dosage reduction of oxazepam  and warnings: dependence and withdrawal reactions ] . acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations,  mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance tolerance to oxazepam may develop from continued 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). tolerance to the therapeutic effect of oxazepam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - scopolamine (unii: dl48g20x8x) (scopolamine - unii:dl48g20x8x) - scopolamine transdermal system is indicated in adults for the prevention of: - nausea and vomiting associated with motion sickness. - post-operative nausea and vomiting (ponv) associated with recovery from anesthesia and/or opiate analgesia and surgery. scopolamine is contraindicated in patients with: - angle closure glaucoma [see warnings and precautions (5.1)] . - hypersensitivity to scopolamine or other belladonna alkaloids or to any ingredient or component in the formulation or delivery system. reactions have included rash generalized and erythema [see adverse reactions (6.2), description (11)] . risk summary available data from observational studies and postmarketing reports with scopolamine use in pregnant women have not identified a drug associated risk of major birth defects, miscarriage, or adverse fetal outcomes. avoid use of scopolamine transdermal system in pregnant women with severe preeclampsia because eclamptic seizures have been reported after exposure to scopolamine (see data) . in animal stu

ABD - İngilizce - NLM (National Library of Medicine)

preferred pharmaceuticals, inc. - clonazepam (unii: 5pe9fde8gb) (clonazepam - unii:5pe9fde8gb) - clonazepam 0.5 mg - seizure disorders clonazepam tablets, usp are useful alone or as an adjunct in the treatment of the lennox-gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures. in patients with absence seizures (petit mal) who have failed to respond to succinimides, clonazepam may be useful. some loss of effect may occur during the course of clonazepam treatment (see precautions, loss of effect ). panic disorder clonazepam tablets, usp are indicated for the treatment of panic disorder, with or without agoraphobia, as defined in dsm-v. panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. the efficacy of clonazepam was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the dsm-iiir category of panic disorder (see clinical pharmacology, clinical trials

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - diclofenac sodium 16.05 mg in 1 ml - diclofenac sodium topical solution is indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s) (1). diclofenac sodium is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product. [see warnings and precautions ( 5.7 , 5.9 )] . - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions ( 5.7 , 5.8 )] . - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1) ] . pregnancy category c prior to 30 weeks gestation; category d starting 30 weeks gestation risk summary use of nsaids, including diclofenac sodium, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. avoid use of nsaids, including diclofenac

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - hydrocodone bitartrate (unii: no70w886kk) (hydrocodone - unii:6yks4y3wq7), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - hydrocodone bitartrate and acetaminophen tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve hydrocodone bitartrate and acetaminophen tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): - have not been tolerated, or are not expected to be tolerated - have not provided adequate analgesia, or are not expected to provide adequate analgesia hydrocodone bitartrate and acetaminophen tablets are contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings ] - hypersensitivity to hydrocodone or acetaminophen

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - ipratropium bromide (unii: j697uz2a9j) (ipratropium - unii:gr88g0i6ul), albuterol sulfate (unii: 021sef3731) (albuterol - unii:qf8svz843e) - ipratropium bromide anhydrous 0.5 mg in 3 ml - ipratropium bromide and albuterol sulfate inhalation solution is indicated for the treatment of bronchospasm associated with copd in patients requiring more than one bronchodilator. ipratropium bromide and albuterol sulfate inhalation solution is contraindicated in patients with a history of hypersensitivity to any of its components, or to atropine and its derivatives. ipratropium bromide and albuterol sulfate inhalation solution 0.5 mg/3 mg per 3 ml  read this patient information completely every time your prescription is filled as information may have changed. keep these instructions with your medication as you may want to read them again. ipratropium bromide and albuterol sulfate inhalation solution should only be used under the direction of a physician. your physician and pharmacist have more information about ipratropium bromide and albuterol sulfate inhalation solution and the condition for which it has been prescribed. contact them if you have additional questions. storing your medicine store ipratrop

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.9) and warnings and precautions (5.4)]. starting duloxetine delayed-release capsules 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 (2.10) and warnings and precautions (5.4)] . risk summary data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see data) . there are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to snris and ssris, including duloxetine delayed-release capsules, during pregnancy (see clinical considerations) . in rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (mrhd) of 120 mg/day given to adolescents on a mg/m2 basis. when duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the mrhd given to adolescents on a mg/m2 basis. at this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. post-weaning growth was not adversely affected. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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. pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. it is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. maternal adverse reactions use of duloxetine delayed-release capsules in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)] . fetal/neonatal adverse reaction neonates exposed to duloxetine and other snris or ssris 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, tremor, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of the snris or ssris, 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 (5.4)] . data human data data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% ci: 1.08 to 2.18). the same study did not find a clinically meaningful increase in the risk for major birth defects in the comparison of 2532 women exposed to duloxetine in the first trimester of pregnancy to 1,284,827 unexposed women after adjusting for several confounders. methodologic limitations include possible residual confounding, misclassification of exposure and outcomes, lack of direct measures of disease severity, and lack of information about alcohol use, nutrition, and over-the-counter medication exposures. animal data in animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. when duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of malformations or developmental variations at doses up to 45 mg/kg/day [3 and 6 times, respectively, the mrhd of 120 mg/day given to adolescents on a mg/m2 basis]. however, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the mrhd in rats and 2 times the mrhd in rabbits). when duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the mrhd given to adolescents on a mg/m2 basis); the no-effect dose was 10 mg/kg/day. furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. risk summary data from published literature report the presence of duloxetine in human milk (see data) . there are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk (see clinical considerations) . there are no data on the effect of duloxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for duloxetine delayed-release capsules and any potential adverse effects on the breastfed child from duloxetine delayed-release capsules or from the underlying maternal condition. clinical considerations infants exposed to duloxetine delayed-release capsules should be monitored for sedation, poor feeding and poor weight gain. data disposition of duloxetine delayed-release capsules was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. the women were given 40 mg of duloxetine delayed-release capsules twice daily for 3.5 days. the peak concentration measured in breast milk occurred at a median of 3 hours after the dose. the amount of duloxetine hydrochloride in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day, which is less than 1% of the maternal dose. the presence of duloxetine hydrochloride metabolites in breast milk was not examined. the safety and effectiveness of duloxetine delayed-release capsules have been established for treatment of generalized anxiety disorder (gad) in patients 7 to 17 years of age and for treatment of juvenile fibromyalgia syndrome in patients 13 to 17 years of age. the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients with major depressive disorder (mdd), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. monitor all pediatric patients being treated with antidepressants for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment, or at times of dosage changes [see warnings and precautions (5.1)] . perform regular monitoring of weight and growth in pediatric patients treated with duloxetine delayed-release capsules [see adverse reactions (6.1)] . generalized anxiety disorder use of duloxetine delayed-release capsules for the treatment of gad in patients 7 to 17 years of age is supported by one 10-week, placebo-controlled trial (gad-6). the study included 272 pediatric patients with gad of which 47% were 7 to 11 years of age (53% were 12 to 17 years of age). duloxetine delayed-release capsules demonstrated superiority over placebo as measured by greater improvement in the pediatric anxiety rating scale (pars) for gad severity score [see clinical studies (14.3)] . the safety and effectiveness of duloxetine delayed-release capsules for the treatment of gad in pediatric patients less than 7 years of age have not been established. fibromyalgia use of duloxetine delayed-release capsules for treatment of fibromyalgia in patients 13 to 17 years of age is supported by a 13-week placebo-controlled trial in 184 patients with juvenile fibromyalgia syndrome (study fm-4). duloxetine delayed-release capsules showed improvement over placebo on the primary endpoint, change from baseline to end-of-treatment on the brief pain inventory (bpi) – modified short form: adolescent version 24-hour average pain severity rating [see clinical studies (14.5)] . the safety and effectiveness of duloxetine delayed-release capsules for the treatment of fibromyalgia in patients less than 13 years of age have not been established. major depressive disorder the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients for the treatment of mdd. efficacy of duloxetine delayed-release capsules was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients aged 7 to 17 years old with mdd (mdd-6 and mdd-7). neither duloxetine delayed-release capsules nor an active control (approved for treatment of pediatric mdd) was superior to placebo. the most frequently observed adverse reactions in the mdd pediatric clinical trials included nausea, headache, decreased weight, and abdominal pain. decreased appetite and weight loss have been observed in association with the use of ssris and snris. juvenile animal toxicology data duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. these effects were observed at the high dose of 45 mg/kg/day (2 times the mrhd, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the mrhd, for a child). geriatric exposure in premarketing clinical trials of duloxetine delayed-release capsules - of the 2,418 patients in mdd trials, 6% (143) were 65 years of age or over. - of the 1,041 patients in clbp trials, 21% (221) were 65 years of age or over. - of the 487 patients in oa trials, 41% (197) were 65 years of age or over. - of the 1,074 patients in the dpnp trials, 33% (357) were 65 years of age or over. - of the 1,761 patients in fm trials, 8% (140) were 65 years of age or over. in the mdd, gad, dpnp, fm, oa, and clbp studies, no overall differences in safety or effectiveness were generally observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between these geriatric and younger adult patients, but greater sensitivity of some older patients cannot be ruled out. ssris and snris, including duloxetine delayed-release capsules have been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.13)] . in an analysis of data from all placebo-controlled-trials, duloxetine delayed-release capsule-treated patients reported a higher rate of falls compared to placebo-treated patients. the increased risk appears to be proportional to a patient’s underlying risk for falls. underlying risk appears to increase steadily with age. as geriatric patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during duloxetine delayed-release capsules treatment is unclear. falls with serious consequences including bone fractures and hospitalizations have been reported with duloxetine delayed-release capsules use [see warnings and precautions (5.3) and adverse reactions (6.1)] . the pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). there was no difference in the cmax , but the auc of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. dosage adjustment based on the age of the adult patient is not necessary. duloxetine’s half-life is similar in men and women. dosage adjustment based on gender is not necessary. duloxetine bioavailability (auc) appears to be reduced by about one-third in smokers. dosage modifications are not recommended for smokers. no specific pharmacokinetic study was conducted to investigate the effects of race. patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. after a single 20 mg dose of duloxetine delayed-release capsules, 6 cirrhotic patients with moderate liver impairment (child-pugh class b) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (auc). although cmax was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see dosage and administration (2.7) and warnings and precautions (5.14)] . limited data are available on the effects of duloxetine in patients with end-stage renal disease (esrd). after a single 60 mg dose of duloxetine, cmax and auc values were approximately 100% greater in patients with esrd receiving chronic intermittent hemodialysis than in subjects with normal renal function. the elimination half-life, however, was similar in both groups. the aucs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. population pk analyses suggest that mild to moderate degrees of renal impairment (estimated crcl 30 to 80 ml/min) have no significant effect on duloxetine apparent clearance [see dosage and administration (2.7) and warnings and precautions (5.14)] . in animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. while duloxetine delayed-release capsules have not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing 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 a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine delayed-release capsules (e.g., development of tolerance, incrementation of dose, drug-seeking behavior). in drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve oxycodone hydrochloride 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. oxycodone hydrochloride tablets are contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment or hypercarbia [see warnings and precautions (5.7)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warn

ABD - İngilizce - NLM (National Library of Medicine)

actavis pharma, inc. - dalfampridine (unii: bh3b64okl9) (dalfampridine - unii:bh3b64okl9) - dalfampridine extended-release tablets are indicated as a treatment to improve walking in adult patients with multiple sclerosis (ms). this was demonstrated by an increase in walking speed [see clinical studies (14)]. the use of dalfampridine is contraindicated in the following conditions: - history of seizure [see warnings and precautions (5.1)] - moderate or severe renal impairment (crcl ≤50 ml/min) [see warnings and precautions (5.2)] - history of hypersensitivity to dalfampridine or 4-aminopyridine; reactions have included anaphylaxis [see warnings and precautions (5.4)] risk summary there are no adequate data on the developmental risk associated with use of dalfampridine in pregnant women. administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at clinically relevant doses [see data] . in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% an