संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

citron pharma llc - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 5 mg - escitalopram tablets are indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [see clinical studies (14.1)] . 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. escitalopram tablets are indicated for the acute treatment of generalized anxiety disorder (gad) in adults [see clinical studies (14.2)] . generalized anxiety disorder (dsm-iv) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

cima labs inc. - modafinil (unii: r3uk8x3u3d) (modafinil - unii:r3uk8x3u3d) - modafinil 100 mg - modafinil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (osa), or shift work disorder (swd). limitations of use in osa, modafinil is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. if continuous positive airway pressure (cpap) is the treatment of choice for a patient, a maximal effort to treat with cpap for an adequate period of time should be made prior to initiating and during treatment with modafinil for excessive sleepiness. modafinil is contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see warnings and precautions (5.1, 5.2, 5.3)] . pregnancy category c there are no adequate and well-controlled studies of modafinil in pregnant women. intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of r- and s-modafinil) and armodafinil (the r-enantiomer of modafinil). although the pharmacology of modafinil is not identical to that of the sympathomimetic amines, it does share some pharmacologic properties with this class. certain of these drugs have been associated with intrauterine growth restriction and spontaneous abortions. whether the cases reported with modafinil are drug-related is unknown. in studies of modafinil and armodafinil conducted in rats (modafinil, armodafinil) and rabbits (modafinil), developmental toxicity was observed at clinically relevant plasma exposures. modafinil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. modafinil (50, 100, or 200 mg/kg/day) administered orally to pregnant rats throughout organogenesis caused, in the absence of maternal toxicity, an increase in resorptions and an increased incidence of visceral and skeletal variations in the offspring at the highest dose tested. the higher no-effect dose for embryofetal developmental toxicity in rats (100 mg/kg/day) was associated with a plasma modafinil auc less than that in humans at the recommended human dose (rhd) of modafinil (200 mg/day). however, in a subsequent study of up to 480 mg/kg/day of modafinil, no adverse effects on embryofetal development were observed. oral administration of armodafinil (60, 200, or 600 mg/kg/day) to pregnant rats throughout organogenesis resulted in increased incidences of fetal visceral and skeletal variations and decreased fetal body weight at the highest dose tested. the highest no-effect dose for embryofetal developmental toxicity in rats (200 mg/kg/day) was associated with a plasma armodafinil auc less than that in humans at the rhd of modafinil. modafinil administered orally to pregnant rabbits throughout organogenesis at doses of up to 100 mg/kg/day had no effect on embryofetal development; however, the doses used were too low to adequately assess the effects of modafinil on embryofetal development.  in a subsequent developmental toxicity study evaluating doses of 45, 90, and 180 mg/kg/day in pregnant rabbits, the incidences of fetal structural alterations and embryofetal death were increased at the highest dose. the highest no-effect dose for developmental toxicity (100 mg/kg/day) was associated with a plasma modafinil auc similar to that in humans at the rhd of modafinil. modafinil administration to rats throughout gestation and lactation at oral doses of up to 200 mg/kg/day resulted in decreased viability in the offspring at doses greater than 20 mg/kg/day, a dose resulting in a plasma modafinil auc less than that in humans at the rhd of modafinil. no effects on postnatal developmental and neurobehavioral parameters were observed in surviving offspring. pregnancy registry a pregnancy registry has been established to collect information on the pregnancy outcomes of women exposed to modafinil. healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-866-404-4106 (toll free). it is not known whether modafinil or its metabolites are excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when modafinil is administered to a nursing woman. safety and effectiveness in pediatric patients have not been established. modafinil is not approved in this population for any indication. serious skin rashes, including erythema multiforme major (emm) and stevens-johnson syndrome (sjs) have been associated with modafinil use in pediatric patients [see warnings and precautions (5.1)] . in a controlled 6-week study, 165 pediatric patients (aged 5-17 years) with narcolepsy were treated with modafinil (n=123), or placebo (n=42). there were no statistically significant differences favoring modafinil over placebo in prolonging sleep latency as measured by mslt, or in perceptions of sleepiness as determined by the clinical global impression-clinician scale (cgi-c). in the controlled and open-label clinical studies, treatment emergent adverse reactions of the psychiatric and nervous system included tourette’s syndrome, insomnia, hostility, increased cataplexy, increased hypnagogic hallucinations, and suicidal ideation. transient leukopenia, which resolved without medical intervention, was also observed. in the controlled clinical study, 3 of 38 girls, ages 12 or older, treated with modafinil experienced dysmenorrhea compared to 0 of 10 girls who received placebo. there were three 7 to 9 week, double-blind, placebo-controlled, parallel group studies in children and adolescents (aged 6-17 years) with attention-deficit hyperactivity disorder (adhd). two of the studies were flexible-dose studies (up to 425 mg/day), and the third was a fixed-dose study (340 mg/day for patients <30 kg and 425 mg/day for patients ≥30 kg). although these studies showed statistically significant differences favoring modafinil over placebo in reducing adhd symptoms as measured by the adhd-rs (school version), there were 3 cases of serious rash including one case of possible sjs among 933 patients exposed to modafinil in this program. modafinil is not approved for use in treating adhd. in clinical trials, experience in a limited number of modafinil-treated patients who were greater than 65 years of age showed an incidence of adverse reactions similar to other age groups. in elderly patients, elimination of modafinil and its metabolites may be reduced as a consequence of aging. therefore, consideration should be given to the use of lower doses and close monitoring in this population [see dosage and administration (2.4) and clinical pharmacology (12.3)]. in patients with severe hepatic impairment, the dose of modafinil should be reduced to one-half of that recommended for patients with normal hepatic function [see dosage and administration (2.3) and clinical pharmacology (12.3)] . modafinil contains modafinil, a schedule iv controlled substance. in humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other cns stimulants. in in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. in some studies, modafinil was also partially discriminated as stimulant-like. physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior). the abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled cns stimulants (methylphenidate). in one placebo-controlled clinical trial, the effects of modafinil withdrawal were monitored following 9 weeks of modafinil use. there were no reported withdrawal symptoms with modafinil during 14 days of observation, although sleepiness returned in narcoleptic patients.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

ajanta pharma usa 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 or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)]. starting duloxetine 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 (2.9) and warnings and precautions (5.4)]. pregnancy

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

ranbaxy pharmaceuticals inc. - pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s) - pioglitazone 15 mg - pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see clinical studies (14)] . pioglitazone tablets exert their antihyperglycemic effect only in the presence of endogenous insulin. pioglitazone tablets should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. use caution in patients with liver disease [see warnings and precautions (5.3)] . do not initiate in patients with nyha class iii or iv heart failure [see boxed warning] . do not use in patients with a history of a serious hypersensitivity reaction to pioglitazone tablets or any of their ingredients. pregnancy category c. there are no adequate and well-controlled studies of pioglitazone tablets in pregnant women. animal studies show increased rates of post-implantation loss, delayed development, reduced fetal weights, and delayed parturition at doses 10 to 40 times the maximum r

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

camber pharmaceuticals inc. - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline 25 mg - major depressive disorder – sertraline hydrochloride is indicated for the treatment of major depressive disorder in adults. the efficacy of sertraline hydrochloride in the treatment of a major depressive episode was established in six to eight week controlled trials of adult outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical trials under clinical pharmacology). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the antidepressant action of sertraline hydrochloride in hos

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - amlodipine 5 mg - amlodipine and olmesartan medoxomil tablets are indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (cv) events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with amlodipine and olmesartan medoxomil tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. amlodipine and olmesartan medoxomil tablets may also be used as initial therapy in patients who are likely to need multiple antihypertensive agents to achieve their blood pressure goals. patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. individual blood pressure goals may vary based upon the patient’s risk. data from an 8-week, placebo-controlled, parallel-group factorial study [see clinical studies (14.1) ] provide estimates of the probability of reaching a blood pressure goal with amlodipine and olmesartan medoxomil tablets compared to amlodipine or olmesartan medoxomil monotherapy. the figures below provide estimates of the likelihood of achieving the targeted systolic or diastolic blood pressure goals with amlodipine and olmesartan medoxomil tablets 10/40 mg compared with amlodipine or olmesartan medoxomil monotherapy, based upon baseline systolic or diastolic blood pressure. the curve of each treatment group was estimated by logistic regression modeling from all available data of that treatment group. the right tail of each curve is less reliable because of small numbers of subjects with high baseline blood pressures. figure 1: probability of achieving systolic blood pressure (sbp) < 140 mmhg at week 8 with locf figure 2: probability of achieving diastolic blood pressure (dbp) < 90 mmhg at week 8 with locf figure 3: probability of achieving systolic blood pressure (sbp) < 130 mmhg at week 8 with locf figure 4: probability of achieving diastolic blood pressure (dbp) < 80 mmhg at week 8 with locf the figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal (e.g., week 8 sbp <140 mmhg or <130 mmhg or a dbp <90 mmhg or <80 mmhg) for the high-dose treatment groups evaluated in the study. amlodipine and olmesartan medoxomil tablets 5/20 mg, the lowest dose combination treatment group, increases the probability of reaching blood pressure goal compared with the highest dose monotherapies, amlodipine 10 mg and olmesartan medoxomil 40 mg. for example, a patient with a baseline blood pressure of 160/100 mmhg has about a 48% likelihood of achieving a goal of <140 mmhg (systolic) and a 51% likelihood of achieving a goal of <90 mmhg (diastolic) on monotherapy with olmesartan medoxomil 40 mg, and about a 46% likelihood of achieving a goal of <140 mmhg (systolic) and a 60% likelihood of achieving a goal of <90 mmhg (diastolic) on monotherapy with amlodipine 10 mg. the likelihood of achieving these same goals increases to 63% (systolic) and 71% (diastolic) on amlodipine and olmesartan medoxomil tablets 5/20 mg, and to 68% (systolic) and 85% (diastolic) on amlodipine and olmesartan medoxomil tablets 10/40 mg. do not co-administer aliskiren with amlodipine and olmesartan medoxomil tablets in patients with diabetes [see drug interactions (7.2)] . risk summary amlodipine and olmesartan medoxomil tablets can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations] . most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue amlodipine and olmesartan medoxomil tablets as soon as possible. consider alternative antihypertensive therapy during pregnancy. 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 hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions olmesartan medoxomil oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan, if oliguria or hypotension occur, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function [see use in specific populations (8.4)]. data animal data no reproductive studies have been conducted with the combination of olmesartan medoxomil, and amlodipine. however, these studies have been conducted for olmesartan medoxomil and amlodipine alone. olmesartan medoxomil no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose [mrhd] on a mg/m2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the dose). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricular, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. amlodipine no evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses of up to 10 mg amlodipine/kg/day (respectively about 10 and 20 times the maximum recommended human dose of 10 mg amlodipine on a mg/m2 basis) during their respective periods of major organogenesis (calculations based on a patient weight of 60 kg). however, litter size was significantly decreased (by about 50%), and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. amlodipine maleate has been shown to prolong both the gestational period and the duration of labor in rats at this dose. risk summary there is limited information regarding the presence of amlodipine and olmesartan medoxomil tablets in human milk, the effects on the breastfed infant, or the effects on milk production. amlodipine is present in human milk. olmesartan is present in rat milk [see data]. because of the potential for adverse effects on the nursing infant, advise a nursing woman that breastfeeding is not recommended during treatment with amlodipine and olmesartan medoxomil tablets. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [14c] olmesartan medoxomil to lactating rats. the safety and effectiveness of amlodipine and olmesartan medoxomil tablets in pediatric patients have not been established. of the total number of subjects in the double-blind clinical study of amlodipine and olmesartan medoxomil tablets, 20% (384/1940) were 65 years of age or older and 3% (62/1940) were 75 years or older. no overall differences in safety or effectiveness were observed between subjects 65 years of age or older and younger subjects. elderly patients have decreased clearance of amlodipine. starting amlodipine or adding amlodipine at 2.5 mg in patients ≥75 years old is recommended. the lowest dose of amlodipine and olmesartan medoxomil tablets is 5/20 mg; therefore, initial therapy with amlodipine and olmesartan medoxomil tablets is not recommended in patients ≥75 years old. amlodipine. 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. elderly patients have decreased clearance of amlodipine with a resulting increase of auc of approximately 40% to 60%, and a lower initial dose may be required. olmesartan medoxomil. of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. 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. there are no studies of amlodipine and olmesartan medoxomil tablets in patients with hepatic insufficiency, but both amlodipine and olmesartan medoxomil show moderate increases in exposure in patients with hepatic impairment. the recommended initial dose of amlodipine in patients with severe hepatic impairment is 2.5 mg, a dose not available with amlodipine and olmesartan medoxomil tablets. amlodipine. amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with severely impaired hepatic function [see warnings and precautions (5.5)] . olmesartan medoxomil . increases in auc0-∞ and peak plasma concentration (cmax ) for olmesartan were observed with moderate hepatic impairment compared to those in matched controls with an increase in auc of about 60%. there are no studies of amlodipine and olmesartan medoxomil tablets in patients with renal impairment. amlodipine. the pharmacokinetics of amlodipine are not significantly influenced by renal impairment. patients with renal failure may therefore receive the usual initial dose. olmesartan medoxomil. patients with renal insufficiency have elevated serum concentrations of olmesartan compared with patients with normal renal function. after repeated dosing, auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min). of the total number of subjects in the double-blind clinical study of amlodipine and olmesartan medoxomil tablets, 25% (481/1940) were black patients. amlodipine and olmesartan medoxomil tablets was effective in treating black patients (usually a low-renin population), and the magnitude of blood pressure reduction in black patients approached that observed for non-black patients.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

dr. reddys laboratories limited - ropinirole hydrochloride (unii: d7zd41rzi9) (ropinirole - unii:030pyr8953) - ropinirole 2 mg - ropinirole extended-release tablets are indicated for the treatment of parkinson’s disease. ropinirole extended-release tablets are contraindicated in patients known to have a hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or any of the excipients. risk summary there are no adequate data on the developmental risk associated with the use of ropinirole extended-release tablets in pregnant women. in animal studies, ropinirole had adverse effects on development when administered to pregnant rats at doses similar to (neurobehavioral impairment) or greater than (teratogenicity and embryolethality at >36 times) the mrhd for parkinson’s disease. ropinirole doses associated with teratogenicity and embryolethality in pregnant rats were associated with maternal toxicity. in pregnant rabbits, ropinirole potentiated the teratogenic effects of l-dopa when these drugs were administered in combination [see data] .   in the u.s. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. the background risk of major birth defects and miscarriage in the indicated populations is unknown.   data animal data: oral administration of ropinirole (0, 20, 60, 90, 120, or 150 mg/kg/day) to pregnant rats during organogenesis resulted in embryolethality, increased incidence of fetal malformations (digit, cardiovascular, and neural tube defects) and variations, and decreased fetal weight at the 2 highest doses. these doses were also associated with maternal toxicity. the highest no-effect dose for adverse effects on embryofetal development (90 mg/kg/day) is approximately 36 times the mrhd for parkinson’s disease (24 mg/day) on a body surface area (mg/m2 ) basis.   no effect on embryofetal development was observed in rabbits when ropinirole was administered alone during organogenesis at oral doses of 0, 1, 5, or 20 mg/kg/day (up to 16 times the mrhd on a mg/m2  basis). in pregnant rabbits, there was a greater incidence and severity of fetal malformations (primarily digit defects) when ropinirole (10 mg/kg/day) was administered orally during gestation in combination with l-dopa (250 mg/kg/day) than when l-dopa was administered alone. this drug combination was also associated with maternal toxicity.   oral administration of ropinirole (0, 0.1, 1, or 10 mg/kg/day) to rats during late gestation and continuing throughout lactation resulted in neurobehavioral impairment (decreased startle response) and decreased body weight in offspring at the highest dose. the no-effect dose of 1 mg/kg/day is less than the mrhd on a mg/m2 basis. risk summary there are no data on the presence of ropinirole in human milk, the effects of ropinirole on the breastfed infant, or the effects of ropinirole on milk production. however, inhibition of lactation is expected because ropinirole inhibits secretion of prolactin in humans. ropinirole or metabolites, or both, are present in rat milk.   the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ropinirole extended-release tablets and any potential adverse effects on the breastfed infant from ropinirole or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. dose adjustment is not necessary in elderly (65 years and older) patients, as the dose of ropinirole extended-release tablets is individually titrated to clinical therapeutic response and tolerability. pharmacokinetic trials conducted in patients demonstrated that oral clearance of ropinirole is reduced by 15% in patients older than 65 years compared with younger patients [see clinical pharmacology (12.3) ]. in flexible-dose clinical trials of ropinirole extended-release, 387 patients were 65 years and older and 107 patients were 75 years and older. among patients receiving ropinirole extended-release, hallucination was more common in elderly patients (10%) compared with non-elderly patients (2%). in these trials, the incidence of overall adverse reactions increased with increasing age for both patients receiving ropinirole extended-release and placebo. in the fixed-dose clinical trials of ropinirole extended-release, 176 patients were 65 years and older and 73 were 75 and older. among patients with advanced parkinson’s disease receiving ropinirole extended-release, vomiting and nausea were more common in patients greater than 65 years (5% and 9%, respectively) compared with patients less than 65 (1% and 7%, respectively). no dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 ml/min). for patients with end-stage renal disease on hemodialysis, a reduced maximum dose is recommended [see dosage and administration (2.2), clinical pharmacology (12.3) ]. the use of ropinirole extended-release tablets in patients with severe renal impairment (creatinine clearance <30 ml/min) without regular dialysis has not been studied. the pharmacokinetics of ropinirole have not been studied in patients with hepatic impairment. 

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

ascend laboratories, llc - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - amlodipine 5 mg - amlodipine and olmesartan medoxomil tablets is indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular  (cv) events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with amlodipine and olmesartan medoxomil tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. amlodipine and olmesartan medoxomil tablets may also be used as initial therapy in patients who are likely to need multiple antihypertensive agents to achieve their blood pressure goals. patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. individual blood pressure goals may vary based upon the patient’s risk. data from an 8-week, placebo-controlled, parallel-group factorial study [see clinical studies (14.1) ] provide estimates of the probability of reaching a blood pressure goal with amlodipine and olmesartan medoxomil tablets compared to amlodipine or olmesartan medoxomil monotherapy. the figures below provide estimates of the likelihood of achieving the targeted systolic or diastolic blood pressure goals with amlodipine and olmesartan medoxomil tablets 10/40 mg compared with amlodipine or olmesartan medoxomil monotherapy, based upon baseline systolic or diastolic blood pressure. the curve of each treatment group was estimated by logistic regression modeling from all available data of that treatment group. the right tail of each curve is less reliable because of small numbers of subjects with high baseline blood pressures.   figure 1: probability of achieving systolic blood pressure (sbp) < 140 mmhg at week 8 with locf    figure 2: probability of achieving diastolic blood pressure (dbp) < 90 mmhg at week 8 with locf   figure 3: probability of achieving systolic blood pressure (sbp) < 130 mmhg at week 8 with locf   figure 4: probability of achieving diastolic blood pressure (dbp) < 80 mmhg at week 8 with locf the figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal (e.g., week 8 sbp <140 mmhg or <130 mmhg or a dbp <90 mmhg or <80 mmhg) for the high-dose treatment groups evaluated in the study. amlodipine and olmesartan medoxomil tablets 5/20 mg, the lowest dose combination treatment group, increases the probability of reaching blood pressure goal compared with the highest dose monotherapies, amlodipine 10 mg and olmesartan medoxomil 40 mg. for example, a patient with a baseline blood pressure of 160/100 mmhg has about a 48% likelihood of achieving a goal of <140 mmhg (systolic) and a 51% likelihood of achieving a goal of <90 mmhg (diastolic) on monotherapy with olmesartan medoxomil 40 mg, and about a 46% likelihood of achieving a goal of <140 mmhg (systolic) and a 60% likelihood of achieving a goal of <90 mmhg (diastolic) on monotherapy with amlodipine 10 mg. the likelihood of achieving these same goals increases to 63% (systolic) and 71% (diastolic) on amlodipine and olmesartan medoxomil tablets 5/20 mg, and to 68% (systolic) and 85% (diastolic) on amlodipine and olmesartan medoxomil tablets 10/40 mg. do not co-administer aliskiren with amlodipine and olmesartan medoxomil tablets in patients with diabetes [see drug interactions (7.2 )]. risk summary amlodipine and olmesartan medoxomil tablets can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations]. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue amlodipine and olmesartan medoxomil tablets as soon as possible. consider alternative antihypertensive therapy during pregnancy. 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 hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions olmesartan medoxomil oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan, if oliguria or hypotension occur, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function [see use in specific populations (8.4)]. data animal data no reproductive studies have been conducted with the combination of olmesartan medoxomil, and amlodipine. however, these studies have been conducted for olmesartan medoxomil and amlodipine alone. olmesartan medoxomil no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose [mrhd] on a mg/m2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricular, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. amlodipine no evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses of up to 10 mg amlodipine/kg/day (respectively about 10 and 20 times the maximum recommended human dose of 10 mg amlodipine on a mg/m2 basis) during their respective periods of major organogenesis (calculations based on a patient weight of 60 kg). however, litter size was significantly decreased (by about 50%), and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. amlodipine maleate has been shown to prolong both the gestational period and the duration of labor in rats at this dose. risk summary there is limited information regarding the presence of amlodipine and olmesartan medoxomil tablets in human milk, the effects on the breastfed infant, or the effects on milk production. amlodipine is present in human milk. olmesartan is present in rat milk [see data] . because of the potential for adverse effects on the nursing infant, advise a nursing woman that breastfeeding is not recommended during treatment with amlodipine and olmesartan medoxomil tablets. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [14 c] olmesartan medoxomil to lactating rats.  the safety and effectiveness of amlodipine and olmesartan medoxomil tablets in pediatric patients have not been established. of the total number of subjects in the double-blind clinical study of amlodipine and olmesartan medoxomil tablets, 20% (384/1940) were 65 years of age or older and 3% (62/1940) were 75 years or older. no overall differences in safety or effectiveness were observed between subjects 65 years of age or older and younger subjects. elderly patients have decreased clearance of amlodipine. starting amlodipine or adding amlodipine at 2.5 mg in patients ≥75 years old is recommended. the lowest dose of amlodipine and olmesartan medoxomil tablets is 5/20 mg; therefore, initial therapy with amlodipine and olmesartan medoxomil tablets is not recommended in patients ≥75 years old. amlodipine. 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. elderly patients have decreased clearance of amlodipine with a resulting increase of auc of approximately 40% to 60%, and a lower initial dose may be required. olmesartan medoxomil.  of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. 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.  there are no studies of amlodipine and olmesartan medoxomil tablets in patients with hepatic insufficiency, but both amlodipine and olmesartan medoxomil show moderate increases in exposure in patients with hepatic impairment. the recommended initial dose of amlodipine in patients with severe hepatic impairment is 2.5 mg, a dose not available with amlodipine and olmesartan medoxomil tablets.   amlodipine.  amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½ ) is 56 hours in patients with severely impaired hepatic function [see warnings and precautions (5.5)] .   olmesartan medoxomil . increases in auc0-∞ and peak plasma concentration (cmax ) for olmesartan were observed with moderate hepatic impairment compared to those in matched controls with an increase in auc of about 60%. there are no studies of amlodipine and olmesartan medoxomil tablets in patients with renal impairment. amlodipine.  the pharmacokinetics of amlodipine are not significantly influenced by renal impairment. patients with renal failure may therefore receive the usual initial dose. olmesartan medoxomil. patients with renal insufficiency have elevated serum concentrations of olmesartan compared with patients with normal renal function. after repeated dosing, auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min). of the total number of subjects in the double-blind clinical study of amlodipine and olmesartan medoxomil tablets, 25% (481/1940) were black patients. amlodipine and olmesartan medoxomil tablets was effective in treating black patients (usually a low-renin population), and the magnitude of blood pressure reduction in black patients approached that observed for non-black patients.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

takeda pharmaceuticals america, inc. - vortioxetine hydrobromide (unii: tks641koay) (vortioxetine - unii:3o2k1s3wqv) - vortioxetine 5 mg - brintellix is indicated for the treatment of major depressive disorder (mdd). the efficacy of brintellix was established in six 6 to 8 week studies (including one study in the elderly) and one maintenance study in adults [see clinical studies (14)] . pregnancy category c risk summary there are no adequate and well-controlled studies of brintellix in pregnant women. vortioxetine caused developmental delays when administered during pregnancy to rats and rabbits at doses 15 and 10 times the maximum recommended human dose (mrhd) of 20 mg, respectively. developmental delays were also seen after birth in rats at doses 20 times the mrhd of vortioxetine given during pregnancy and through lactation. there were no teratogenic effects in rats or rabbits at doses up to 77 and 58 times, the mrhd of vortioxetine, respectively, given during organogenesis. the incidence of malformations in human pregnancies has not been established for brintellix. all human pregnancies, regardless of drug exposure, have a background rate of

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline 50 mg - zoloft (sertraline hydrochloride) is indicated for the treatment of major depressive disorder in adults. the efficacy of zoloft in the treatment of a major depressive episode was established in six to eight week controlled trials of adult outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical trials under clinical pharmacology). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the antidepressant action of zoloft in hospitalized depressed patients has not been adequately st