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bryant ranch prepack - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9) - omeprazole delayed-release capsules is indicated for short-term treatment of active duodenal ulcer in adults. most patients heal within four weeks. some patients may require an additional four weeks of therapy. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with h. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate h. pylori in adults. dual therapy omeprazole delayed-release capsules in combination with clarithromycin is indicated for treatment of patients with h. pylori infection and duodenal ulcer disease to eradicate h . pylori in adults. among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin is more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. in patients who fail therapy, susceptibility

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impax generics - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate 400 mg - felbamate tablets, usp are not indicated as a first line antiepileptic treatment (see warnings ). felbamate tablets, usp are recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgement, felbamate tablets, usp can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate is contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a history of any blood dysc

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pharmaceutical associates, inc. - lactulose (unii: 9u7d5qh5ae) (lactulose - unii:9u7d5qh5ae) - for the treatment of constipation. in patients with a history of chronic constipation, lactulose solution therapy increases the number of bowel movements per day and the number of days on which bowel movements occur. since lactulose solution contains galactose (less than 1.6 g/15 ml), it is contraindicated in patients who require a low galactose diet.

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amneal pharmaceuticals ny llc - pilocarpine hydrochloride (unii: 0ww6d218xj) (pilocarpine - unii:01mi4q9di3) - pilocarpine hydrochloride ophthalmic solution is indicated for the: none. pregnancy category c. animal reproduction studies have not been conducted with pilocarpine hydrochloride. it is also not known whether pilocarpine hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. pilocarpine hydrochloride ophthalmic solution should be given to a pregnant woman only if clearly needed. it is not known whether this drug is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when pilocarpine hydrochloride ophthalmic solution is administered to a nursing woman. safety and effectiveness of pilocarpine hydrochloride ophthalmic solution in pediatric patients have been established.   no overall differences in safety or effectiveness have been observed between elderly and younger patients.

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amneal pharmaceuticals ny llc - pilocarpine hydrochloride (unii: 0ww6d218xj) (pilocarpine - unii:01mi4q9di3) - pilocarpine hydrochloride ophthalmic solution is indicated for the: none. pregnancy category c. animal reproduction studies have not been conducted with pilocarpine hydrochloride. it is also not known whether pilocarpine hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. pilocarpine hydrochloride ophthalmic solution should be given to a pregnant woman only if clearly needed. it is not known whether this drug is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when pilocarpine hydrochloride ophthalmic solution is administered to a nursing woman. safety and effectiveness of pilocarpine hydrochloride ophthalmic solution in pediatric patients have been established.   no overall differences in safety or effectiveness have been observed between elderly and younger patients.

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bryant ranch prepack - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole sodium delayed-release tablets, usp are indicated for: pantoprazole is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (ee). for those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established. pantoprazole is indicated for maintenance of healing of ee and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gerd. controlled studies did not extend beyond 12 months. pantoprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. - pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria[see warnings and precautions (5.2),  adverse reactions (6 )] . pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria[see warnings and precautions (5.2),  adverse reactions (6 )] . - proton pump inhibitors (ppis), including pantoprazole, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . proton pump inhibitors (ppis), including pantoprazole, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)] . risk summary available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole. in animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see data) . a pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (pnd) 4 through pnd 21 [see use in specific populations (8.4)] . there were no drug-related findings in maternal animals. advise pregnant women of the potential risk of fetal harm. 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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (ppis). there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=0.55, [95% confidence interval (ci) 0.08-3.95]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations or=1.12 ([95% ci 0.86-1.45] and for spontaneous abortions or=1.29 [95% ci 0.84-1.97]). animal data reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. the studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. a pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. on postnatal day (pnd 4) through pnd 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in humans at a dose of 40 mg). there were no drug-related findings in maternal animals. during the preweaning dosing phase (pnd 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (auc) in humans receiving the 40 mg dose) and higher doses. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. the femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. there were no microscopic changes in the distal femur, proximal tibia, or stifle joints. changes in bone parameters were partially reversible following a recovery period, with findings on pnd 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. risk summary pantoprazole has been detected in breast milk of a nursing mother after a single 40 mg oral dose of pantoprazole. there were no effects on the breastfed infant (see data) . there are no data on pantoprazole effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pantoprazole and any potential adverse effects on the breastfed child from pantoprazole or from the underlying maternal condition. data the breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/l and 24 mcg/l, respectively. a milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. pantoprazole was not detectable (<10 mcg/l) in milk at 6, 8 and 24 hours after the dose. the relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. no adverse events in the infant were reported by the mother. the safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of ee associated with gerd have been established in pediatric patients 1 year through 16 years of age. effectiveness for ee has not been demonstrated in patients less than 1 year of age. in addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. therefore, pantoprazole is indicated for the short-term treatment of ee associated with gerd for patients 5 years and older. the safety and effectiveness of pantoprazole for pediatric uses other than ee have not been established. 1 year through 16 years of age use of pantoprazole in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of ee associated with gerd is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of pantoprazole for treatment of ee associated with gerd in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see clinical studies (14.1), clinical pharmacology (12.3)] . safety of pantoprazole in the treatment of ee associated with gerd in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with ee (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). the children ages 1 year to 5 years with endoscopically diagnosed ee (defined as an endoscopic hetzel-dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole (approximating 0.6 mg/kg or 1.2 mg/kg). all 4 of these patients with ee were healed (hetzel-dent score of 0 or 1) at 8 weeks. because ee is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic gerd were also included in these studies. patients were treated with a range of doses of pantoprazole once daily for 8 weeks. for safety findings see adverse reactions (6.1) . because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of pantoprazole for symptomatic gerd in the pediatric population. the effectiveness of pantoprazole for treating symptomatic gerd in pediatric patients has not been established. although the data from the clinical trials support use of pantoprazole for the short-term treatment of ee associated with gerd in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see dosage and administration (2 )] . in a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven gerd had a median value of 2.4 l/h. following a 1.2 mg/kg equivalent dose (15 mg for ≤ 12.5 kg and 20 mg for > 12.5 to < 25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. the estimated auc for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean auc value of 6.8 mcg•hr/ml. neonates to less than one year of age pantoprazole was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. patients were enrolled if they had symptomatic gerd based on medical history and had not responded to non-pharmacologic interventions for gerd for two weeks. patients received pantoprazole daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive pantoprazole treatment or placebo for the subsequent four weeks in a double-blind manner. efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. there was no statistically significant difference between pantoprazole and placebo in the rate of discontinuation. in this trial, the adverse reactions that were reported more commonly (difference of ≥ 4%) in the treated population compared to the placebo population were elevated ck, otitis media, rhinitis, and laryngitis. in a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with gerd compared to adults who received a single 40 mg dose (geometric mean auc was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). in these patients, the apparent clearance (cl/f) increased with age (median clearance: 0.6 l/hr, range: 0.03 to 3.2 l/hr). these doses resulted in pharmacodynamic effects on gastric but not esophageal ph. following once daily dosing of 2.5 mg of pantoprazole in preterm infants and neonates, there was an increase in the mean gastric ph (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 60% at baseline to 80% at steady-state). following once daily dosing of approximately 1.2 mg/kg of pantoprazole in infants 1 through 11 months of age, there was an increase in the mean gastric ph (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 32% at baseline to 60% at steady-state). however, no significant changes were observed in mean intraesophageal ph or % time that esophageal ph was < 4 in either age group. because pantoprazole was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of pantoprazole for treatment of symptomatic gerd in infants less than 1 year of age is not indicated. animal toxicity data in a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (pnd 4) through pnd 21, in addition to lactational exposure through milk. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in children aged 6 to 11 years at the 40 mg dose) and higher doses. changes in bone parameters were partially reversible following a recovery period. in neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. an increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. full to partial recovery of these effects were noted in animals of both age groups following a recovery period. in short-term us clinical trials, ee healing rates in the 107 elderly patients (≥ 65 years old) treated with pantoprazole were similar to those found in patients under the age of 65. the incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

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hospira, inc. - bupivacaine hydrochloride (unii: 7tqo7w3vt8) (bupivacaine - unii:y8335394ro) - bupivacaine hydrochloride anhydrous 2.5 mg in 1 ml - marcaine / marcaine with epinephrine is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. specific concentrations and presentations of marcaine / marcaine with epinephrine are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see dosage and administration (2.2)]. limitations of use not all blocks are indicated for use with marcaine / marcaine with epinephrine given clinically significant risks associated with use [see dosage and administration (2.2), contraindications (4), warnings and precautions (5.1, 5.4, 5.5, 5.7, 5.9)] . marcaine / marcaine with epinephrine is contraindicated in: risk summary marcaine / marcaine with epinephrine is contraindicated for obstetrical paracervical block anesthesia. its use in this technique has resulted in fetal bradycardia and death [see contraindications (4), warnings and precautions (5.1)] . there are no available data on use of marcaine / marcaine with epinephrine in pregnant women to inform a drug-associated risk of adverse developmental outcomes. in animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at clinically relevant doses. decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a dose level comparable to the daily maximum recommended human dose (mrhd) on a body surface area (bsa) basis. based on animal data, advise pregnant women of the potential risks to a fetus (see data). local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see clinical pharmacology (12.3)]. the incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. adverse reactions in the parturient, fetus, and neonate involve alterations of the cns, peripheral vascular tone, and cardiac function. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. clinical considerations maternal adverse reactions maternal hypotension has resulted from regional anesthesia. local anesthetics produce vasodilation by blocking sympathetic nerves. the supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. elevating the patient's legs will also help prevent decreases in blood pressure. the fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable. labor or delivery epidural, caudal, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. epidural anesthesia has been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. the use of obstetrical anesthesia may increase the need for forceps assistance. the use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. this has not been reported with bupivacaine. it is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to parturients. to do this, the patient must be maintained in the left lateral decubitus position or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. data animal data bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses. bupivacaine hydrochloride was administered subcutaneously to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3, 5.8, & 22.2 mg/kg during the period of organogenesis (implantation to closure of the hard palate). the high doses are comparable to the daily mrhd of 400 mg/day on a mg/m2 bsa basis. no embryo-fetal effects were observed in rats at the high dose which caused increased maternal lethality. an increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity with the fetal no observed adverse effect level representing approximately 0.3 times the mrhd on a bsa basis. in a rat pre- and post-natal developmental study (dosing from implantation through weaning) conducted at subcutaneous doses of 4.4, 13.3, & 40 mg/kg, decreased pup survival was observed at the high dose. the high dose is comparable to the daily mrhd of 400 mg/day on a bsa basis. risk summary lactation studies have not been conducted with bupivacaine. bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. marcaine / marcaine with epinephrine should be administered to lactating women only if clearly indicated. studies assessing the effects of marcaine / marcaine with epinephrine in breastfed children have not been performed. studies to assess the effect of marcaine / marcaine with epinephrine on milk production or excretion have not been performed. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bupivacaine and any potential adverse effects on the breastfed child from bupivacaine or from the underlying maternal condition. marcaine / marcaine with epinephrine is approved for use in adults. administration of marcaine / marcaine with epinephrine in pediatric patients younger than 12 years is not recommended. continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities. patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with marcaine / marcaine with epinephrine. in clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients. differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see clinical pharmacology (12.3)] . this product is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. elderly patients may require lower doses of marcaine / marcaine with epinephrine. amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with marcaine / marcaine with epinephrine, especially with repeat doses [see warnings and precautions (5.10)] . bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. this should be considered when selecting the marcaine / marcaine with epinephrine dosage [see use in specific populations (8.5)] .

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winthrop u.s, a business of sanofi-aventis u.s. llc - clofarabine (unii: 762rdy0y2h) (clofarabine - unii:762rdy0y2h) - clofarabine 1 mg in 1 ml - clofarabine is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. this indication is based upon response rate. there are no trials verifying an improvement in disease-related symptoms or increased survival with clofarabine. none. risk summary in animal reproduction studies, intravenous administration of clofarabine to pregnant rats and rabbits during organogenesis at doses approximately 0.2 to 1-times the maximum recommended human dose of 52 mg/m 2 based on body surface area (bsa) resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities (see data) . advise pregnant women of the potential risk to a fetus. there are no available data on clofarabine use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. clofarabine should be used during pregnancy only if the potential benefits to the mother outweigh the potential risks, including those to the 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 intravenous administration of clofarabine to pregnant rats during organogenesis (gestation days [gd] 7–17) at doses of 1, 3 or 9 mg/kg/day (equivalent to 6, 18, 54 mg/m 2 /day) resulted in maternal toxicities at the 9 mg/kg dose, as indicated by reduced body weights and food consumption. developmental toxicity (i.e., reduced fetal body weights and increased postimplantation loss) and increased incidences of external, soft tissue, and skeletal malformations and variations (including retarded ossification) were observed at 9 mg/kg/day (54 mg/m 2 ; approximately equivalent to the recommended human dose based on bsa). altered ossification patterns (extra metacarpal or metatarsal ossification) were observed in single fetuses at lower doses of clofarabine (1 and 3 mg/kg/day; 0.1- and 0.3-times the recommended human dose based on bsa). when clofarabine was administered intravenously to pregnant rabbits during organogenesis (gd 6–18) at doses of 0.1, 0.3, or 1 mg/kg/day (equivalent to 1.2, 3.6, 12 mg/m 2 /day), developmental toxicity (i.e., reduced fetal body weights and increased postimplantation loss) and increased incidences of external, soft tissue, and skeletal malformations and variations (including retarded ossification) were observed at the 1 mg/kg/day dose (12 mg/m 2 ; 0.2-times the recommended human dose based on bsa). alterations in ossification patterns (increase in the average numbers of ossified thoracic vertebrae and rib pairs, and reduction in the average number of forepaw metacarpals) and abdominal wall defect were observed at 0.3 mg/kg/day (3.6 mg/m 2 ; 0.1-times the recommended human dose based on bsa). risk summary there are no data on the presence of clofarabine in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in the breastfed child including genotoxicity, advise patients not to breastfeed during treatment with clofarabine, and for at least 2 weeks after the last dose. pregnancy testing pregnancy testing is recommended for females of reproductive potential prior to initiating clofarabine. contraception females clofarabine can cause embryo-fetal harm when administered to pregnant women [see use in specific populations (8.1)] . advise female patients to use effective contraception during treatment with clofarabine and for 6 months after the last dose. males based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with clofarabine and for at least 3 months after the last dose [see nonclinical toxicology (13.1)] . infertility females based on findings from animal studies, clofarabine may impair female fertility [see nonclinical toxicology (13.1)]. the reversibility of the effect on fertility is unknown. males based on findings from animal studies, clofarabine may impair male fertility [see nonclinical toxicology (13.1)]. the reversibility of the effect on fertility is unknown. safety and effectiveness have been established in pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia. safety and effectiveness of clofarabine has not been established in geriatric patients aged 65 and older. safety and effectiveness have not been established in adults. reduce the clofarabine starting dose by 50% in patients with crcl of 30 to 60 ml/min. there is insufficient information to make a dosage recommendation in patients with crcl less than 30 ml/min or in patients on dialysis. the pharmacokinetics of clofarabine in patients with renal impairment and normal renal function were obtained from a population pharmacokinetic analysis of three pediatric and two adult studies. in patients with crcl 60 to less than 90 ml/min (n=47) and crcl 30 to less than 60 ml/min (n=30), the average auc of clofarabine increased by 60% and 140%, respectively, compared to patients with normal (n=66) renal function (crcl greater than 90 ml/min).

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nucare pharmaceuticals,inc. - paroxetine hydrochloride hemihydrate (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paroxetine tablets, usp are indicated for the treatment of major depressive disorder. the efficacy of paroxetine tablets, usp in the treatment of a major depressive episode was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical pharmacology —clinical trials ). 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 effects of paroxetine tablets, usp in hospitalized depressed patients have not been adequately studie

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remedyrepack inc. - spironolactone (unii: 27o7w4t232) (spironolactone - unii:27o7w4t232) - spironolactone tablets are indicated for treatment of nyha class iii–iv heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. spironolactone tablets are usually administered in conjunction with other heart failure therapies. spironolactone tablets are indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. 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. spironolactone tablets are indicated for the management of edema in the following settings: - cirrhosis of the liver when edema is not responsive to fluid and sodium restriction. - nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response. because it increases serum potassium, spironolactone tablets may be useful for treating edema when administration of other diuretics has caused hypokalemia. spironolactone tablets are indicated in the following settings: - short-term preoperative treatment of patients with primary hyperaldosteronism. - long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery. - long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism). spironolactone tablets are contraindicated in the patients with: - hyperkalemia - addison's disease - concomitant use of eplerenone risk summary based on mechanism of action and findings in animal studies, spironolactone may affect sex differentiation of the male during embryogenesis (see data) . rat embryofetal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. limited available data from published case reports and case series did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone . there are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy (see clinical considerations) . because of the potential risk to the male fetus due to anti-androgenic properties of spironolactone and animal data, avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male 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. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnant women with congestive heart failure are at increased risk for preterm birth. stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. clinical classification of heart disease may worsen with pregnancy and lead to maternal death. closely monitor pregnant patients for destabilization of their heart failure. pregnant women with symptomatic cirrhosis generally have poor outcomes including hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction and maternal death. outcomes are worse with coexisting esophageal varices. pregnant women with cirrhosis of the liver should be carefully monitored and managed accordingly. 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. data animal data teratology studies with spironolactone have been carried out in mice and rabbits at doses of up to 20 mg/kg/day. on a body surface area basis, this dose in the mouse is substantially below the maximum recommended human dose and, in the rabbit, approximates the maximum recommended human dose. no teratogenic or other embryotoxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits. because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, spironolactone may have the potential for adversely affecting sex differentiation of the male during embryogenesis. when administered to rats at 200 mg/kg/day between gestation days 13 and 21 (late embryogenesis and fetal development), feminization of male fetuses was observed. offspring exposed during late pregnancy to 50 and 100 mg/kg/day doses of spironolactone exhibited changes in the reproductive tract including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction, that persisted into adulthood. spironolactone has known endocrine effects in animals including progestational and antiandrogenic effects. risk summary spironolactone is not present in breastmilk; however, limited data from a lactating woman at 17 days postpartum reports the presence of the active metabolite, canrenone, in human breast milk in low amounts that are expected to be clinically inconsequential. in this case, there were no adverse effects reported for the breastfed infant after short term exposure to spironolactone; however, long term effects on a breastfed infant are unknown. there are no data on spironolactone effects on milk production. consider the developmental and health benefits of breastfeeding along with the mother's clinical need for spironolactone and any potential adverse effects on the breastfed child from spironolactone or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. spironolactone is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, monitor renal function. spironolactone is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. patients with renal impairment are at increased risk of hyperkalemia. monitor potassium closely. spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma in patients with hepatic disease with cirrhosis and ascites. in these patients, initiate spironolactone in the hospital [see dosage and administration (2.4)and clinical pharmacology (12.3)] . clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. in patients with cirrhosis, start with lowest initial dose and titrate slowly [see dosage and administration (2.4)and clinical pharmacology (12.3)] .