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

proficient rx lp - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin anhydrous 750 mg - to reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin tabletsand other antibacterial drugs, levofloxacin tabletsshould be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. levofloxacin tablets are indicated for the treatment of adults (≥ 18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed in this section. culture and susceptibility testing appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see micr

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

proficient rx lp - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin anhydrous 750 mg - levofloxacin tablets are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed in this section. levofloxacin is indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli, klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae . adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see clinical studies (14.1)] . levofloxacin is indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae (including  multi-drug-resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae,

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

rising pharma holdings, inc. - galantamine hydrobromide (unii: mj4ptd2vvw) (galantamine - unii:0d3q044kca) - galantamine 4 mg - galantamine tablets are indicated for the treatment of mild to moderate dementia of the alzheimer’s type. galantamine tablets are contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation. risk summary there are no adequate data on the developmental risk associated with the use of galantamine hydrobromide in pregnant women. in studies conducted in animals, administration of galantamine during pregnancy resulted in developmental toxicity (increased incidence of morphological abnormalities and decreased growth in offspring) at doses similar to or greater than those used clinically (see data). in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data in rats, administration of galantamine (oral doses of 2, 8, or 16 mg/kg/day), from day 14 (females) or day 60 (males) prior to mating and continuing in females through the period of organogenesis, resulted in an increased incidence of fetal skeletal variations at the two highest doses, which were associated with maternal toxicity. the no-effect dose for embryo-fetal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the maximum recommended human dose (mrhd) of 24 mg/day on a body surface area (mg/m2 ) basis. when galantamine (oral doses of 4, 12, 28, or 40 mg/kg/day) was administered to pregnant rabbits throughout the period of organogenesis, small increases in fetal visceral malformations and skeletal variations were observed at the highest dose which was associated with maternal toxicity. the no-effect dose for embryo-fetal developmental toxicity in rabbits (28 mg/kg/day) is approximately 20 times the mrhd on a mg/m2 basis. in a study in which pregnant rats were orally dosed with galantamine (2, 8, or 16 mg/kg/day) from the beginning of organogenesis through day 21 post-partum, pup weights were decreased at birth and during the lactation period at the two highest doses. the no-effect dose for pre- and postnatal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the mrhd on a mg/m2 basis. risk summary there are no data on the presence of galantamine in human milk, the effects on the breastfed infant, or the effects of galantamine hydrobromide on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for galantamine hydrobromide and any potential adverse effects on the breastfed infant from galantamine hydrobromide or from the underlying maternal condition. the safety and effectiveness in pediatric patients have not been established. eight double-blind, placebo-controlled clinical trials and 5 open-label trials in a total of 6519 patients have investigated galantamine hydrobromide in the treatment of mild to moderate dementia of the alzheimer’s type [see adverse reactions (6.1) and clinical studies (14)] . the mean age of patients enrolled in these clinical studies was 75 years; 78% of these patients were between 65 and 84 years of age, and 10% of patients were 85 years of age or older. in patients with moderate hepatic impairment, a dosage adjustment is recommended. the use of galantamine hydrobromide in patients with severe hepatic impairment is not recommended [see dosage and administration (2.3) and clinical pharmacology (12.3)] . in patients with a creatinine clearance of 9 to 59 ml/min, a dosage adjustment is recommended. the use of galantamine hydrobromide in patients with creatinine clearance less than 9 ml/min is not recommended [see dosage and administration (2.4) and clinical pharmacology (12.3)] .

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

aurobindo pharma limited - galantamine hydrobromide (unii: mj4ptd2vvw) (galantamine - unii:0d3q044kca) - galantamine 4 mg - galantamine tablets are indicated for the treatment of mild to moderate dementia of the alzheimer’s type. galantamine tablets are contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation. risk summary there are no adequate data on the developmental risk associated with the use of galantamine hydrobromide in pregnant women. in studies conducted in animals, administration of galantamine during pregnancy resulted in developmental toxicity (increased incidence of morphological abnormalities and decreased growth in offspring) at doses similar to or greater than those used clinically (see data). in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data in rats, administration of galantamine (oral doses of 2, 8, or 16 mg/kg/day), from day 14 (females) or day 60 (males) prior to mating and continuing in females through the period of organogenesis, resulted in an increased incidence of fetal skeletal variations at the two highest doses, which were associated with maternal toxicity. the no-effect dose for embryo-fetal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the maximum recommended human dose (mrhd) of 24 mg/day on a body surface area (mg/m2 ) basis. when galantamine (oral doses of 4, 12, 28, or 40 mg/kg/day) was administered to pregnant rabbits throughout the period of organogenesis, small increases in fetal visceral malformations and skeletal variations were observed at the highest dose which was associated with maternal toxicity. the no-effect dose for embryo-fetal developmental toxicity in rabbits (28 mg/kg/day) is approximately 20 times the mrhd on a mg/m2 basis. in a study in which pregnant rats were orally dosed with galantamine (2, 8, or 16 mg/kg/day) from the beginning of organogenesis through day 21 post-partum, pup weights were decreased at birth and during the lactation period at the two highest doses. the no-effect dose for pre- and postnatal developmental toxicity in rats (2 mg/kg/day) is approximately equal to the mrhd on a mg/m2 basis. risk summary there are no data on the presence of galantamine in human milk, the effects on the breastfed infant, or the effects of galantamine hydrobromide on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for galantamine hydrobromide and any potential adverse effects on the breastfed infant from galantamine hydrobromide or from the underlying maternal condition. the safety and effectiveness in pediatric patients have not been established. eight double-blind, placebo-controlled clinical trials and 5 open-label trials in a total of 6519 patients have investigated galantamine hydrobromide in the treatment of mild to moderate dementia of the alzheimer’s type [see adverse reactions (6.1) and clinical studies (14)] . the mean age of patients enrolled in these clinical studies was 75 years; 78% of these patients were between 65 and 84 years of age, and 10% of patients were 85 years of age or older. in patients with moderate hepatic impairment, a dosage adjustment is recommended. the use of galantamine hydrobromide in patients with severe hepatic impairment is not recommended [see dosage and administration (2.3) and clinical pharmacology (12.3)] . in patients with a creatinine clearance of 9 to 59 ml/min, a dosage adjustment is recommended. the use of galantamine hydrobromide in patients with creatinine clearance less than 9 ml/min is not recommended [see dosage and administration (2.4) and clinical pharmacology (12.3)] .

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

proficient rx lp - ciprofloxacin hydrochloride (unii: 4ba73m5e37) (ciprofloxacin - unii:5e8k9i0o4u) - ciprofloxacin 250 mg - ciprofloxacin tablets usp, 250 mg and 500 mg is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions and patient populations listed below. please see error! hyperlink reference not valid. for specific recommendations. urinary tract infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, serratia marcescens, proteus mirabilis, providencia rettgeri, morganella morganii, citrobacter diversus, citrobacter freundii, pseudomonas aeruginosa, methicillin-susceptible staphylococcus epidermidis, staphylococcus saprophyticus, or enterococcus faecalis. acute uncomplicated cystitis in females caused by escherichia coli or staphylococcus saprophyticus. chronic bacterial prostatitis caused by escherichia coli or proteus mirabilis. lower respiratory tract infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, pseudomonas aeruginosa, haemophilus influen

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

pd-rx pharmaceuticals, inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam 15 mg - meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weigh ≥60 kg [ see dosage and administration ( 2.4) and clinical studies ( 14.2) ]. meloxicam tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reac

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

actavis pharma, inc. - clindamycin phosphate (unii: eh6d7113i8) (clindamycin - unii:3u02el437c), tretinoin (unii: 5688utc01r) (tretinoin - unii:5688utc01r) - clindamycin 12 mg in 1 g - clindamycin phosphate and tretinoin gel 1.2% / 0.025% is indicated for the topical treatment of acne vulgaris in patients 12 years or older. clindamycin phosphate and tretinoin gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis. pregnancy category c. there are no well-controlled trials in pregnant women treated with clindamycin phosphate and tretinoin gel. clindamycin phosphate and tretinoin gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. clindamycin phosphate and tretinoin gel was tested for maternal and developmental toxicity in new zealand white rabbits with topical doses of 60, 180 and 600 mg/kg/day. clindamycin phosphate and tretinoin gel at 600 mg/kg/day (approximately 12 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison) was considered to be the no-observed-adverse-effect level (noael) for maternal and developmental toxicity following dermal administration of clindamycin phosphate and tretinoin gel for two weeks prior to artificial insemination and continuing until gestation day 18, inclusive. for purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of clindamycin phosphate and tretinoin gel applied daily to a 60 kg person. clindamycin teratology (segment ii) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity. tretinoin in oral segment iii studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~ 78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison). with widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). the significance of these spontaneous reports in terms of risk to the fetus is not known. dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on a body surface area comparison. oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on a body surface area comparison. it is not known whether clindamycin is excreted in human milk following use of clindamycin phosphate and tretinoin gel. however, orally and parenterally administered clindamycin has been reported to appear in breast milk. because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. it is not known whether tretinoin is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when clindamycin phosphate and tretinoin gel is administered to a nursing woman. safety and effectiveness of clindamycin phosphate and tretinoin gel in pediatric patients under the age of 12 have not been established. clinical trials of clindamycin phosphate and tretinoin gel included patients 12 to 17 years of age. [see clinical studies (14)] clinical studies of clindamycin phosphate and tretinoin gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

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

rising pharma holdings, inc. - clarithromycin (unii: h1250jik0a) (clarithromycin - unii:h1250jik0a) - clarithromycin 250 mg - clarithromycin tablets are indicated in adults for the treatment of mild to moderate infections caused by susceptible isolates due to haemophilus influenzae , haemophilus parainfluenzae , moraxella catarrhalis , or streptococcus pneumoniae [see indications and usage (1.9)]. clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to haemophilus influenzae , moraxella catarrhalis , or streptococcus pneumoniae [see indications and usage (1.9)]. clarithromycin tablets are indicated [see indications and usage (1.9)] for the treatment of mild to moderate infections caused by susceptible isolates due to: - haemophilus influenzae (in adults)  - mycoplasma pneumoniae , streptococcus pneumoniae , chlamydophila pneumoniae (clarithromycin tablets [in adults and pediatric patients]) clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to streptococcus pyogenes as an alternative in individuals who cannot use first line therapy. clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to staphylococcus aureus , or streptococcus pyogenes . clarithromycin tablets are indicated in pediatric patients for the treatment of mild to moderate infections caused by susceptible isolates due to haemophilus influenzae , moraxella catarrhalis , or streptococcus pneumoniae [see clinical studies (14.2)] . clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to mycobacterium avium or mycobacterium intracellulare in patients with advanced hiv infection [see clinical studies (14.1)] . clarithromycin tablets are given in combination with other drugs in adults as described below to eradicate h. pylori . the eradication of h. pylori has been demonstrated to reduce the risk of duodenal ulcer recurrence [see clinical studies (14.3)] . - clarithromycin tablets in combination with amoxicillin and prevacid (lansoprazole) or prilosec (omeprazole) delayed-release capsules, as triple therapy, are indicated for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate h. pylori . - clarithromycin tablets in combination with prilosec (omeprazole) capsules are indicated for the treatment of patients with an active duodenal ulcer associated with h. pylori infection. regimens which contain clarithromycin tablets as the single antibacterial agent are more likely to be associated with the development of clarithromycin resistance among patients who fail therapy. clarithromycin-containing regimens should not be used in patients with known or suspected clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting. there is resistance to macrolides in certain bacterial infections caused by streptococcus pneumoniae and staphylococcus aureus . susceptibility testing should be performed when clinically indicated. to reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin tablets and other antibacterial drugs, clarithromycin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. clarithromycin tablets are contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs [see warnings and precautions (5.1)] . concomitant administration of clarithromycin tablets with cisapride and pimozide is contraindicated [see drug interactions (7)] . there have been postmarketing reports of drug interactions when clarithromycin is co-administered with cisapride or pimozide, resulting in cardiac arrhythmias (qt prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes ) most likely due to inhibition of metabolism of these drugs by clarithromycin tablets. fatalities have been reported. clarithromycin tablets are contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin. concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment. concomitant administration of clarithromycin tablets with lomitapide is contraindicated due to potential for markedly increased transaminases [see warnings and precautions (5.4) and drug interactions (7)] . concomitant administration of clarithromycin tablets with hmg-coa reductase inhibitors (statins) that are extensively metabolized by cyp3a4 (lovastatin or simvastatin) is contraindicated, due to the increased risk of myopathy, including rhabdomyolysis [see warnings and precautions (5.4) and drug interactions (7)] . concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated [see drug interactions (7)] . concomitant administration of clarithromycin and lurasidone is contraindicated since it may result in an increase in lurasidone exposure and the potential for serious adverse reactions [see drug interactions (7)]. for information about contraindications of other drugs indicated in combination with clarithromycin tablets, refer to their full prescribing information (contraindications section). risk summary based on findings from animal studies, clarithromycin is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. if pregnancy occurs while taking clarithromycin, the patient should be apprised of the potential hazard to the fetus [see warnings and precautions (5.7)]. limited data from a small number of published human studies with clarithromycin use during pregnancy are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, administration of oral clarithromycin to pregnant mice, rats, rabbits, and monkeys during the period of organogenesis produced malformations in rats (cardiovascular anomalies) and mice (cleft palate) at clinically relevant doses based on body surface area comparison. fetal effects in mice, rats, and monkeys (e.g., reduced fetal survival, body weight, body weight gain) and implantation losses in rabbits were generally considered to be secondary to maternal toxicity (see data). 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 animal reproduction studies were conducted in mice, rats, rabbits, and monkeys with oral and intravenously administered clarithromycin. in pregnant mice, clarithromycin was administered during organogenesis (gestation day [gd] 6 to 15) at oral doses of 15, 60, 250, 500, or 1000 mg/kg/day. reduced body weight observed in dams at 1000 mg/kg/day (3 times the maximum recommended human dose [mrhd] based on body surface area comparison) resulted in reduced survival and body weight of the fetuses. at ≥ 500 mg/kg/day, increases in the incidence of postimplantation loss and cleft palate in the fetuses were observed. no adverse developmental effects were observed in mice at ≤ 250 mg/kg/day (≤ 1 times mrhd based on body surface area comparison). in pregnant sprague dawley rats, clarithromycin was administered during organogenesis (gd 6 to 15) at oral doses of 15, 50, or 150 mg/kg/day. reductions in body weight and food consumption was observed in dams at 150 mg/kg/day. increased resorptions and reduced body weight of the fetuses at this dose were considered secondary to maternal toxicity. additionally, at 150 mg/kg/day (1 times mrhd based on body surface area comparison), a low incidence of cardiovascular anomalies (complete situs inversus, undivided truncus, iv septal defect) was observed in the fetuses. clarithromycin did not cause adverse developmental effects in rats at 50 mg/kg/day (0.3 times mrhd based on body surface area comparison). intravenous dosing of clarithromycin during organogenesis in rats (gd 6 to 15) at 15, 50, or 160 mg/kg/day was associated with maternal toxicity (reduced body weight, body-weight gain, and food consumption) at 160 mg/kg/day but no evidence of adverse developmental effects at any dose (≤ 1 times mrhd based on body surface area comparison). in pregnant wistar rat, clarithromycin was administered during organogenesis (gd 7 to 17) at oral doses of 10, 40, or 160 mg/kg/day. reduced body weight and food consumption were observed in dams at 160 mg/kg/day but there was no evidence of adverse developmental effects at any dose (≤ 1 times mrhd based on body surface area comparison). in pregnant rabbits, clarithromycin administered during organogenesis (gd 6 to 18) at oral doses of 10, 35, or 125 mg/kg/day resulted in reduced maternal food consumption and decreased body weight at the highest dose, with no evidence of any adverse developmental effects at any dose (≤ 2 times mrhd based on body surface area comparison). intravenously administered clarithromycin to pregnant rabbits during organogenesis (gd 6 to 18) in rabbits at 20, 40, 80, or 160 mg/kg/day (≥ 0.3 times mrhd based on body surface area comparison) resulted in maternal toxicity and implantation losses at all doses. in pregnant monkeys, clarithromycin was administered (gd 20 to 50) at oral doses of 35 or 70 mg/kg/day. dose-dependent emesis, poor appetite, fecal changes, and reduced body weight were observed in dams at all doses (≥ 0.5 times mrhd based on body surface area comparison). growth retardation in 1 fetus at 70 mg/kg/day was considered secondary to maternal toxicity. there was no evidence of primary drug related adverse developmental effects at any dose tested. in a reproductive toxicology study in rats administered oral clarithromycin late in gestation through lactation (gd 17 to post-natal day 21) at doses of 10, 40, or 160 mg/kg/day (≤ 1 times mrhd based on body surface area comparison), reductions in maternal body weight and food consumption were observed at 160 mg/kg/day. reduced body-weight gain observed in offspring at 160 mg/kg/day was considered secondary to maternal toxicity. no adverse developmental effects were observed with clarithromycin at any dose tested. risk summary based on limited human data, clarithromycin and its active metabolite 14-oh clarithromycin are present in human milk at less than 2% of the maternal weight-adjusted dose (see data). in a separate observational study, reported adverse effects on breast-fed children (rash, diarrhea, loss of appetite, somnolence) were comparable to amoxicillin (see data). no data are available to assess the effects of clarithromycin or 14-oh clarithromycin on milk production. the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for clarithromycin and any potential adverse effects on the breast-fed child from clarithromycin or from the underlying maternal condition. data human serum and milk samples were obtained after 3 days of treatment, at steady state, from one published study of 12 lactating women who were taking clarithromycin 250 mg orally twice daily. based on the limited data from this study, and assuming milk consumption of 150 ml/kg/day, an exclusively human milk fed infant would receive an estimated average of 136 mcg/kg/day of clarithromycin and its active metabolite, with this maternal dosage regimen. this is less than 2% of the maternal weight-adjusted dose (7.8 mg/kg/day, based on the average maternal weight of 64 kg), and less than 1% of the pediatric dose (15 mg/kg/day) for children greater than 6 months of age. a prospective observational study of 55 breastfed infants of mothers taking a macrolide antibacterial (6 were exposed to clarithromycin) were compared to 36 breastfed infants of mothers taking amoxicillin. adverse reactions were comparable in both groups. adverse reactions occurred in 12.7% of infants exposed to macrolides and included rash, diarrhea, loss of appetite, and somnolence. males administration of clarithromycin resulted in testicular atrophy in rats, dogs and monkeys [see nonclinical toxicology (13.1)] . the safety and effectiveness of clarithromycin tablets have been established for the treatment of the following conditions or diseases in pediatric patients 6 months and older. use in these indications is based on clinical trials in pediatric patients or adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients: - pharyngitis/tonsillitis - community-acquired pneumonia - acute maxillary sinusitis - acute otitis media [see clinical studies (14.2)] - uncomplicated skin and skin structure infections the safety and effectiveness of clarithromycin tablets have been established for the prevention of disseminated mycobacterium avium complex (mac) disease in pediatric patients 20 months and older with advanced hiv infection. no studies of clarithromycin for mac prophylaxis have been performed in pediatric populations and the doses recommended for prophylaxis are derived from mac pediatric treatment studies. safety and effectiveness of clarithromycin in pediatric patients under 6 months of age have not been established. the safety of clarithromycin has not been studied in mac patients under the age of 20 months. in a steady-state study in which healthy elderly subjects (65 years to 81 years of age) were given 500 mg of clarithromycin every 12 hours, the maximum serum concentrations and area under the curves of clarithromycin and 14-oh clarithromycin were increased compared to those achieved in healthy young adults. these changes in pharmacokinetics parallel known age-related decreases in renal function. in clinical trials, elderly patients did not have an increased incidence of adverse reactions when compared to younger patients. consider dosage adjustment in elderly patients with severe renal impairment. elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients [see warnings and precautions (5.3)] . most reports of acute kidney injury with calcium channel blockers metabolized by cyp3a4 (e.g., verapamil, amlodipine, diltiazem, nifedipine) involved elderly patients 65 years of age or older [see warnings and precautions (5.4)] . especially in elderly patients, there have been reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, some of which occurred in patients with renal insufficiency. deaths have been reported in some patients [see contraindications (4.4) and warnings and precautions (5.4)] . clarithromycin is principally excreted via the liver and kidney. clarithromycin may be administered without dosage adjustment to patients with hepatic impairment and normal renal function. however, in the presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate [see dosage and administration (2.6)] .

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

purdue pharma lp - hydrocodone bitartrate (unii: no70w886kk) (hydrocodone - unii:6yks4y3wq7) - hydrocodone bitartrate 30 mg - hysingla er is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve hysingla er for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - hysingla er is not indicated as an as-needed (prn) analgesic. hysingla er is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.8)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.13,5.14)] - hypersensitivity to hydrocodone or any component of hysingla er. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with hysingla er in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies with hydrocodone in rats and rabbits no embryotoxicity or teratogenicity was observed. however, reduced pup survival rates, reduced fetal/pup body weights, and delayed ossification were observed at doses causing maternal toxicity. in all of the studies conducted, the exposures in animals were less than the human exposure [see data] . the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor and delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. hysingla er is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including hysingla er, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data no evidence of embryotoxicity or teratogenicity was observed after oral administration of hydrocodone throughout the period of organogenesis in rats and rabbits at doses up to 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on auc exposure comparisons). however, in these studies, reduced fetal body weights and delayed ossification were observed in rat at 30 mg/kg/day and reduced fetal body weights were observed in rabbits at 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on auc exposure comparisons). in a pre- and post-natal development study pregnant rats were administered oral hydrocodone throughout the period of gestation and lactation. at a dose of 30 mg/kg/day decreased pup viability, pup survival indices, litter size and pup body weight were observed. this dose is approximately 0.1 times the human hydrocodone dose of 120 mg/day based on auc exposure comparisons. risk summary hydrocodone is present in human milk. a published lactation study reports variable concentrations of hydrocodone and hydromorphone (an active metabolite) in breast milk with administration of immediate-release hydrocodone to nursing mothers in the early post-partum period. this lactation study did not assess breastfed infants for potential adverse drug reactions. lactation studies have not been conducted with hysingla, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with hysingla er. clinical considerations monitor infants exposed to hysingla er through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)] . the safety and effectiveness of hysingla er in pediatric patients have not been established. hysingla er gradually forms a viscous hydrogel (i.e., a gelatinous mass) when exposed to water or other fluids. pediatric patients may be at increased risk of esophageal obstruction, dysphagia, and choking because of a smaller gastrointestinal lumen if they ingest hysingla er [see warnings and precautions (5.13)] . in a controlled pharmacokinetic study, elderly subjects (greater than 65 years) compared to young adults had similar plasma concentrations of hydrocodone [see clinical pharmacology (12.3)] . of the 1827 subjects exposed to hysingla er in the pooled chronic pain studies, 241 (13%) were age 65 and older (including those age 75 and older), while 42 (2%) were age 75 and older. in clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received hysingla er. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of hysingla er slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)] . hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. no adjustment in starting dose with hysingla er is required in patients with mild or moderate hepatic impairment. patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function [see clinical pharmacology (12.3)] . therefore, a dosage reduction is recommended for these patients [see dosage and administration (2.5)] . regularly evaluate closely for respiratory depression, sedation, and hypotension. no dose adjustment is needed in patients with mild renal impairment. patients with moderate or severe renal impairment or end stage renal disease have higher plasma concentrations than those with normal renal function [see clinical pharmacology (12.3)] . therefore, a dosage reduction is recommended for these patients [see dosage and administration (2.6)]. regularly evaluate closely for respiratory depression, sedation, and hypotension. hysingla er contains hydrocodone bitartrate, a schedule ii controlled substance. hysingla er contains hydrocodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of hysingla er increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of hysingla er with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of hysingla er abuse include those with a history of prolonged use of any opioid, including products containing hydrocodone, those with a history of drug or alcohol abuse, or those who use hysingla er in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. hysingla er, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of hysingla er abuse of hysingla er poses a risk of overdose and death. this risk is increased with concurrent use of hysingla er with alcohol and/or other cns depressants [see warnings and precautions (5.1, 5.3), drug interactions (7)]. abuse may occur by taking intact tablets in quantities greater than prescribed or without legitimate purpose, by crushing and chewing or snorting the crushed formulation, or by injecting a solution made from the crushed formulation. taking cut, broken, chewed, crushed, or dissolved hysingla er increases the risk of overdose and death. hysingla er is approved for oral use only. with parenteral abuse, the inactive ingredients in hysingla er can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. abuse deterrence studies hysingla er is formulated with physicochemical properties intended to make the tablet more difficult to manipulate for misuse and abuse, and maintains some extended-release characteristics even if the tablet is physically compromised. to evaluate the ability of these physicochemical properties to reduce the potential for abuse of hysingla er, a series of in vitro laboratory studies, pharmacokinetic studies and clinical abuse potential studies was conducted. a summary is provided at the end of this section. in vitro testing in vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation. results support that hysingla er resists crushing, breaking, and dissolution using a variety of tools and solvents and retains some extended-release properties despite manipulation. when subjected to an aqueous environment, hysingla er gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a hypodermic needle. clinical abuse potential studies studies in non-dependent opioid abusers: two randomized, double-blind, placebo and active-comparator studies in non-dependent opioid abusers were conducted to characterize the abuse potential of hysingla er following physical manipulation and administration via the intranasal and oral routes. for both studies, drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking, and 100 represents maximum liking. response to whether the subject would take the study drug again was measured on a unipolar scale of 0 to 100 where 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”). intranasal abuse potential study: in the intranasal abuse potential study, 31 subjects were dosed and 25 subjects completed the study. treatments studied included intranasally administered tampered hysingla er 60 mg tablets, powdered hydrocodone bitartrate 60 mg, and placebo. incomplete dosing due to granules falling from the subjects’ nostrils occurred in 82% (n = 23) of subjects receiving tampered hysingla er compared to no subjects with powdered hydrocodone or placebo. the intranasal administration of tampered hysingla er was associated with statistically significantly lower mean and median scores for drug liking and take drug again (p <0.001 for both), compared with powdered hydrocodone as summarized in table 4. figure 1 demonstrates a comparison of peak drug liking scores for tampered hysingla er compared with powdered hydrocodone in subjects (n = 25) who received both treatments intranasally. the y-axis represents the percent of subjects attaining a percent reduction in peak drug liking scores for tampered hysingla er vs. hydrocodone powder greater than or equal to the value on the x-axis. approximately 80% (n = 20) of subjects had some reduction in drug liking with tampered hysingla er relative to hydrocodone powder. sixty-eight percent (n = 17) of subjects had a reduction of at least 30% in drug liking with tampered hysingla er compared with hydrocodone powder, and approximately 64% (n = 16) of subjects had a reduction of at least 50% in drug liking with tampered hysingla er compared with hydrocodone powder. approximately 20% (n = 5) of subjects had no reduction in liking with tampered hysingla er relative to hydrocodone powder. figure 1: percent reduction profiles for emax of drug liking vas for manipulated hysingla er vs. hydrocodone powder, n = 25 following intranasal administration oral abuse potential study: in the oral abuse potential study, 40 subjects were dosed and 35 subjects completed the study. treatments studied included oral administrations of chewed hysingla er 60 mg tablets, intact hysingla er 60 mg tablets, 60 mg aqueous hydrocodone bitartrate solution, and placebo. the oral administration of chewed and intact hysingla er was associated with statistically lower mean and median scores on scales that measure drug liking and desire to take drug again (p<0.001), compared to hydrocodone solution as summarized in table 5. figure 2 demonstrates a comparison of peak drug liking scores for chewed hysingla er compared with hydrocodone solution in subjects who received both treatments orally. the y-axis represents the percent of subjects attaining a percent reduction in peak drug liking scores for chewed hysingla er vs. hydrocodone solution greater than or equal to the value on the x-axis. approximately 80% (n = 28) of subjects had some reduction in drug liking with chewed hysingla er relative to hydrocodone solution. approximately 69% (n = 24) of subjects had a reduction of at least 30% in drug liking with chewed hysingla er compared with hydrocodone solution, and approximately 60% (n = 21) of subjects had a reduction of at least 50% in drug liking with chewed hysingla er compared with hydrocodone solution. approximately 20% (n = 7) of subjects had no reduction in drug liking with chewed hysingla er relative to hydrocodone solution. figure 2. percent reduction profiles for emax of drug liking vas for chewed hysingla er vs. hydrocodone solution, n = 35 following oral administration the results of a similar analysis of drug liking for intact hysingla er relative to hydrocodone solution were comparable to the results of chewed hysingla er relative to hydrocodone solution. approximately 83% (n = 29) of subjects had some reduction in drug liking with intact hysingla er relative to hydrocodone solution. eighty-three percent (n = 29) of subjects had a reduction of at least 30% in peak drug liking scores with intact hysingla er compared to hydrocodone solution, and approximately 74% (n = 26) of subjects had a reduction of at least 50% in peak drug liking scores with intact hysingla er compared with hydrocodone solution. approximately 17% (n = 6) had no reduction in drug liking with intact hysingla er relative to hydrocodone solution. summary the in vitro data demonstrate that hysingla er has physical and chemical properties that are expected to deter intranasal and intravenous abuse. the data from the clinical abuse potential studies, along with support from the in vitro data, also indicate that hysingla er has physicochemical properties that are expected to reduce intranasal abuse and oral abuse when chewed. however, abuse of hysingla er by the intravenous, intranasal, and oral routes is still possible. additional data, including epidemiological data, when available, may provide further information on the impact of hysingla er on the abuse liability of the drug. accordingly, this section may be updated in the future as appropriate. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue hysingla er in a patient physically dependent on opioids. rapid tapering of hysingla er in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing hysingla er, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hysingla er the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.7), warnings and precautions (5.16)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] .

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

proficient rx lp - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules are indicated for the treatment of: monoamine oxidase inhibitors (maois) the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)]. starting duloxetine delayed-release capsules in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9) and warnings and precautions (5.4)] . teratogenic effects    pregnancy category c   risk summary there are no adequate and well-controlled studies of duloxetine administration in pregna