Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

aurobindo pharma limited - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - cold sores (herpes labialis) valacyclovir tablets are indicated for treatment of cold sores (herpes labialis). the efficacy of valacyclovir tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. genital herpes initial episode: valacyclovir tablets are indicated for treatment of the initial episode of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir tablets when initiated more than 72 hours after the onset of signs and symptoms has not been established. recurrent episodes:  valacyclovir tablets are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir tablets when initiated more than 24 hours after the onset of signs and symptoms has not been established. suppressive therapy:  valacyclovir tablets are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in hiv-1-infected adults. the efficacy and safety of valacyclovir tablets for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in hiv-1-infected patients have not been established. reduction of transmission:  valacyclovir tablets are indicated for the reduction of transmission of genital herpes in immunocompetent adults. the efficacy of valacyclovir tablets for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established. the efficacy of valacyclovir tablets for the reduction of transmission of genital herpes in individuals with multiple partners and non-heterosexual couples has not been established. safer sex practices should be used with suppressive therapy (see current centers for disease control and prevention [cdc] sexually transmitted diseases treatment guidelines ). herpes zoster valacyclovir tablets are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults. the efficacy of valacyclovir tablets when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets for treatment of disseminated herpes zoster have not been established. cold sores (herpes labialis) valacyclovir tablets are indicated for the treatment of cold sores (herpes labialis) in pediatric patients aged greater than or equal to 12 years. the efficacy of valacyclovir tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. chickenpox valacyclovir tablets are indicated for the treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years. based on efficacy data from clinical trials with oral acyclovir, treatment with valacyclovir tablets should be initiated within 24 hours after the onset of rash [see clinical studies (14.4) ] . the efficacy and safety of valacyclovir tablets have not been established in: - immunocompromised patients other than for the suppression of genital herpes in hiv-1-infected patients with a cd4+ cell count greater than or equal to 100 cells/mm3 . - patients aged less than 12 years with cold sores (herpes labialis). - patients aged less than 2 years or greater than or equal to 18 years with chickenpox. - patients aged less than 18 years with genital herpes. - patients aged less than 18 years with herpes zoster. - neonates and infants as suppressive therapy following neonatal herpes simplex virus (hsv) infection. valacyclovir tablets are contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valacyclovir, acyclovir, or any component of the formulation [see adverse reactions (6.3)] . risk summary clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, have not identified a drug associated risk of major birth defects. there are  insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes (see data). there are risks to the fetus associated with untreated herpes simplex during pregnancy (see clinical considerations). in animal reproduction studies, no evidence of adverse developmental outcomes was observed with valacyclovir when administered to pregnant rats and rabbits at system exposures (auc) 4 (rats) and 7 (rabbits) times the human exposure at the maximum recommended human dose (mrhd) (see data). the estimated background risk of major birth defects and miscarriage for the indicated populations 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: the risk of neonatal hsv infection varies from 30% to 50% for genital hsv acquired in late pregnancy (third trimester), whereas with hsv acquisition in early pregnancy, the risk of neonatal infection is about 1%. a primary herpes occurrence during the first trimester of pregnancy has been associated with neonatal chorioretinitis, microcephaly, and, in rare cases, skin lesions. in very rare cases, transplacental transmission can occur resulting in congenital infection, including microcephaly, hepatosplenomegaly, intrauterine growth restriction, and stillbirth. co-infection with hsv increases the risk of perinatal hiv transmission in women who had a clinical diagnosis of genital herpes during pregnancy. data human data: clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, based on published literature, have not identified a drug-associated risk of major birth defects. there are insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes. the acyclovir and the valacyclovir pregnancy registries, both population-based international prospective studies, collected pregnancy data through april 1999. the acyclovir registry documented outcomes of 1,246 infants and fetuses exposed to acyclovir during pregnancy (756 with earliest exposure during the first trimester, 197 during the second trimester, 291 during the third trimester, and 2 unknown). the occurrence of major birth defects during first-trimester exposure to acyclovir was 3.2% (95% ci: 2.0% to 5.0%) and during any trimester of exposure was 2.6% (95% ci: 1.8% to 3.8%). the valacyclovir pregnancy registry documented outcomes of 111 infants and fetuses exposed to valacyclovir during pregnancy (28 with earliest exposure in the first trimester, 31 during the second trimester, and 52 during the third trimester).the occurrence of major birth defects during first-trimester exposure to valacyclovir was 4.5% (95% ci: 0.24% to 24.9%) and during any trimester of exposure was 3.9% (95% ci: 1.3% to 10.7%). available studies have methodological limitations including insufficient sample size to support conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. animal data: valacyclovir was administered orally to pregnant rats and rabbits (up to  400 mg/kg/day) during organogenesis (gestation days 6 through 15, and 6 through 18, respectively). no adverse embryo-fetal effects were observed in rats and rabbits at acyclovir exposures (auc) of up to approximately 4 (rats) and 7 (rabbits) times the exposure in humans at the mrhd. early embryo death, fetal growth retardation (weight and length), and variations in fetal skeletal development (primarily extra ribs and delayed ossification of sternebrae) were observed in rats and associated with maternal toxicity (200 mg/kg/day; approximately 6 times higher than human exposure at the mrhd). in a pre/postnatal development study, valacyclovir was administered orally to pregnant rats (up to 200 mg/kg/day from gestation day 15 to post-partum day 20) from late gestation through lactation. no significant adverse effects were observed in offspring exposed daily from before birth through lactation at maternal exposures (auc) of approximately 6 times higher than human exposures at the mrhd. risk summary although there is no information on the presence of valacyclovir in human milk, its metabolite, acyclovir, is present in human milk following oral administration of valacyclovir. based on published data, a 500 mg maternal dose of valacyclovir hydrochloride twice daily would provide a breastfed child with an oral acyclovir dosage of approximately 0.6 mg/kg/day (see data). there is no data on the effects of valacyclovir or acyclovir on the breastfed child or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for valacyclovir hydrochloride and any potential adverse effects on the breastfed child from valacyclovir hydrochloride or from the underlying maternal condition. data following oral administration of a 500 mg dose of valacyclovir hydrochloride to 5 lactating women, peak acyclovir concentrations (cmax ) in breast milk ranged from 0.5 to 2.3 times (median 1.4) the corresponding maternal acyclovir serum concentrations. the acyclovir breast milk auc ranged from 1.4 to 2.6 times (median 2.2) maternal serum auc. a 500 mg maternal dose of valacyclovir hydrochloride twice daily would provide a breastfed child with an oral acyclovir dosage of approximately 0.6 mg/kg/day. unchanged valacyclovir was not detected in maternal serum, breast milk or infant urine. valacyclovir hydrochloride is indicated for treatment of cold sores in pediatric patients aged greater than or equal to 12 years and for treatment of chickenpox in pediatric patients aged 2 to less than 18 years [see indications and usage (1.2), dosage and administration (2.2)]. the use of valacyclovir hydrochloride for treatment of cold sores is based on 2 double‑blind, placebo‑controlled clinical trials in healthy adults and adolescents (aged greater than or equal to 12 years) with a history of recurrent cold sores [see clinical studies (14.1)] . the use of valacyclovir hydrochloride for treatment of chickenpox in pediatric patients aged 2 to less than 18 years is based on single-dose pharmacokinetic and multiple-dose safety data from an open-label trial with valacyclovir and supported by efficacy and safety data from 3 randomized, double-blind, placebo-controlled trials evaluating oral acyclovir in pediatric subjects with chickenpox [see dosage and administration (2.2), adverse reactions (6.2), clinical pharmacology (12.3), clinical studies (14.4)] . the efficacy and safety of valacyclovir have not been established in pediatric patients: - aged less than 12 years with cold sores - aged less than 18 years with genital herpes - aged less than 18 years with herpes zoster - aged less than 2 years with chickenpox - for suppressive therapy following neonatal hsv infection. the pharmacokinetic profile and safety of valacyclovir oral suspension in children aged less than 12 years were studied in 3 open-label trials. no efficacy evaluations were conducted in any of the 3 trials. trial 1 was a single-dose pharmacokinetic, multiple-dose safety trial in 27 pediatric subjects aged 1 to less than 12 years with clinically suspected varicella-zoster virus (vzv) infection [see dosage and administration (2.2), adverse reactions (6.2), clinical pharmacology (12.3), clinical studies (14.4)]. trial 2 was a single-dose pharmacokinetic and safety trial in pediatric subjects aged 1 month to less than 6 years who had an active herpes virus infection or who were at risk for herpes virus infection. fifty-seven subjects were enrolled and received a single dose of 25 mg/kg valacyclovir oral suspension. in infants and children aged 3 months to less than 6 years, this dose provided comparable systemic acyclovir exposures to that from a 1 gram dose of valacyclovir in adults (historical data). in infants aged 1 month to less than 3 months, mean acyclovir exposures resulting from a 25 mg/kg dose were higher (cmax : ↑30%, auc: ↑60%) than acyclovir exposures following a 1 gram dose of valacyclovir in adults. acyclovir is not approved for suppressive therapy in infants and children following neonatal hsv infections; therefore, valacyclovir is not recommended for this indication because efficacy cannot be extrapolated from acyclovir. trial 3 was a single-dose pharmacokinetic, multiple-dose safety trial in 28 pediatric subjects aged 1 to less than 12 years with clinically suspected hsv infection. none of the subjects enrolled in this trial had genital herpes. each subject was dosed with valacyclovir oral suspension 10 mg/kg twice daily for 3 to 5 days. acyclovir systemic exposures in pediatric subjects following valacyclovir oral suspension were compared with historical acyclovir systemic exposures in immunocompetent adults receiving the solid oral dosage form of valacyclovir or acyclovir for the treatment of recurrent genital herpes. the mean projected daily acyclovir systemic exposures in pediatric subjects across all age-groups (1 to less than 12 years) were lower (cmax : ↓20%, auc: ↓33%) compared with the acyclovir systemic exposures in adults receiving valacyclovir 500 mg twice daily but were higher (daily auc: ↑16%) than systemic exposures in adults receiving acyclovir 200 mg 5 times daily. insufficient data are available to support valacyclovir for the treatment of recurrent genital herpes in this age-group because clinical information on recurrent genital herpes in young children is limited; therefore, extrapolating efficacy data from adults to this population is not possible. moreover, valacyclovir has not been studied in children aged 1 to less than 12 years with recurrent genital herpes. of the total number of subjects in clinical trials of valacyclovir hydrochloride, 906 were 65 and over, and 352 were 75 and over. in a clinical trial of herpes zoster, the duration of pain after healing (post-herpetic neuralgia) was longer in subjects 65 and older compared with younger adults. elderly patients are more likely to have reduced renal function and require dose reduction. elderly patients are also more likely to have renal or cns adverse events [see dosage and administration (2.4), warnings and precautions (5.2, 5.3), clinical pharmacology (12.3)] . dosage reduction is recommended when administering valacyclovir hydrochloride to patients with renal impairment [see dosage and administration (2.4), warnings and precautions (5.2, 5.3)] .

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - bosutinib monohydrate (unii: 844zje6i55) (bosutinib - unii:5018v4aez0) - bosutinib monohydrate 100 mg - bosulif is indicated for the treatment of: bosulif is contraindicated in patients with a history of hypersensitivity to bosulif. reactions have included anaphylaxis [see adverse reactions (6.1)] . risk summary based on findings from animal studies and its mechanism of action, bosulif can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies conducted in rats and rabbits, oral administration of bosutinib during organogenesis caused adverse developmental outcomes, including structural abnormalities, embryo-fetal mortality, and alterations to growth at maternal exposures (auc) as low as 1.2 times the human exposure at the dose of 500 mg/day (see data ). advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2–4% and 15–20%, respectively. data animal data in a rat fertility and early embryonic development study, bosutinib was administered orally to female rats for approximately 3 to 6 weeks, depending on day of mating (2 weeks prior to cohabitation with untreated breeder males until gestation day [gd] 7). increased embryonic resorptions occurred at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). in an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during the period of organogenesis at doses of 3, 10, and 30 mg/kg/day. at the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae, and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight. the dose of 30 mg/kg/day resulted in exposures (auc) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively. fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats. in a rat pre- and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day. reduced number of pups born occurred at greater than or equal to 30 mg/kg/day bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and increased incidence of total litter loss and decreased growth of offspring after birth occurred at 70 mg/kg/day bosutinib (6.9 and 5.1 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). risk summary no data are available regarding the presence of bosutinib or its metabolites in human milk or its effects on a breastfed child or on milk production. however, bosutinib is present in the milk of lactating rats. because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment with bosulif and for 2 weeks after the last dose. animal data after a single radiolabeled bosutinib dose to lactating rats, radioactivity was present in the plasma of suckling offspring for 24 to 48 hours. based on findings from animal studies, bosulif can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy females of reproductive potential should have a pregnancy test prior to starting treatment with bosulif. contraception females advise females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with bosulif and for 2 weeks after the last dose. infertility the risk of infertility in females or males of reproductive potential has not been studied in humans. based on findings from animal studies, bosulif may cause reduced fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness of bosulif have been established in pediatric patients 1 year of age and older with newly-diagnosed cp ph+ cml and cp ph+ cml that is resistant or intolerant to prior therapy. use of bosulif for these indications is based on data from bchild [nct04258943]. the study included pediatric patients with newly diagnosed cp ph+ cml in the following age groups: 2 patients 1 year of age to less than 6 years of age, 3 patients 6 years of age to less than 12 years of age, and 10 patients 12 years of age to less than 17 years of age. the study also included pediatric patients with cp ph+ cml that was resistant or intolerant to prior therapy in the following age groups: 4 patients 1 year of age to less than 6 years of age, 10 patients 6 years of age to less than 12 years of age, and 10 patients 12 years of age to less than 17 years of age [see adverse reactions (6.1) and clinical studies (14.3) ] . bsa-normalized apparent clearance in 27 pediatric patients aged 4 to <17 years (141.3 l/h/m2 ) was 29% higher than bsa-normalized apparent clearance in adult patients with cp ph+ cml (109.2 l/h/m2 ) [see clinical pharmacology (12.3)] . the recommended dosage of bosulif in pediatric patients is based on body-surface area (bsa) [see dosage and administration (2.1)]. the safety and effectiveness of bosulif in pediatric patients younger than 1 year of age with newly diagnosed cp ph+ cml, pediatric patients younger than 1 year of age with cp ph+ cml that is resistant or intolerant to prior therapy, and pediatric patients with ap ph+ cml or bp ph+ cml have not been established. in the single-arm study in patients with cml who were resistant or intolerant to prior therapy of bosulif in patients with ph+ cml, 20% were age 65 and over, 4% were 75 and over. of the 268 patients who received bosutinib in the study for newly diagnosed cml, 20% were age 65 and over, 5% were 75 and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. reduce the bosulif starting dose in patients with moderate (creatinine clearance [clcr ] 30 to 50 ml/min, estimated by cockcroft-gault (c-g)) and severe (clcr less than 30 ml/min, c-g) renal impairment at baseline. for patients who have declining renal function while on bosulif who cannot tolerate the starting dose, follow dose adjustment recommendations for toxicity [see dosage and administration (2.3, 2.5) and clinical pharmacology (12.3)] . bosulif has not been studied in patients undergoing hemodialysis. reduce the bosulif dosage in patients with hepatic impairment (child-pugh a, b, or c) [see dosage and administration (2.3, 2.5) and clinical pharmacology (12.3)]. bosulif® (bah-su-lif) (bosutinib) capsules this instructions for use contains information on how to prepare and give a dose of bosulif capsules by opening the capsules and mixing the contents with applesauce or yogurt for people who cannot swallow capsules whole. read this instructions for use before you prepare or give the first dose of bosulif, and each time you get a refill. ask your healthcare provider or pharmacist if you have any questions. important information you need to know before preparing a dose of bosulif capsules: preparing a dose of bosulif capsules: gather the following supplies: giving a dose of bosulif capsules: step 1: choose a clean, flat work surface. place all supplies on the work surface. step 2: wash and dry your hands well. step 3: put on disposable gloves step 4: get the prescribed number of bosulif capsule(s) needed to prepare the dose. step 5: add the amount of applesauce or yogurt needed for the prescribed dose to the container. dose amount of applesauce or yogurt 100 mg 10 ml (2 teaspoons) 150 mg 15 ml (3 teaspoons) 200 mg 20 ml (4 teaspoons) 250 mg 25 ml (5 teaspoons) 300 mg 30 ml (6 teaspoons) 350 mg 30 ml (6 teaspoons) 400 mg 35 ml (7 teaspoons) 450 mg 40 ml (8 teaspoons) 500 mg 45 ml (9 teaspoons) 550 mg 45 ml (9 teaspoons) 600 mg 50 ml (10 teaspoons) step 6: carefully open each of the bosulif capsule(s) needed for the dose and empty the entire contents into the applesauce or yogurt. mix the entire capsule contents with the applesauce or yogurt in the container. step 7: swallow all of the mixture right away, without chewing. step 8: dispose of (throw away) the empty bosulif capsule shell(s) in the household trash. step 9: wash teaspoon and the container with soap and warm water. step 10: remove disposable gloves and throw them away in the household trash. step 11: wash and dry your hands. how should i store bosulif capsules? keep bosulif and all medicines out of the reach of children. lab-0639-12.0 for more information, go to www.bosulif.com or www.pfizermedicalinformation.com or call 1-800-438-1985. this instructions for use has been approved by the u.s. food and drug administration. issued: 9 2023

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine 25 mg - quetiapine tablets, usp are indicated for the treatment of schizophrenia. the efficacy of quetiapine fumarate tablets in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (13 to 17 years). the effectiveness of quetiapine fumarate tablets for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [see clinical studies (14.1) ]. quetiapine tablets, usp are indicated for the acute treatment of manic episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10 to 17 years) [see clinical studies (14.2) ]. quetiapine tablets, usp are indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. efficacy was established in two 8-week monotherapy trials

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

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

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

novartis pharmaceuticals corporation - eltrombopag olamine (unii: 4u07f515lg) (eltrombopag - unii:s56d65xj9g) - eltrombopag 12.5 mg - promacta is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia (itp) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. promacta should be used only in patients with itp whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. promacta is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis c to allow the initiation and maintenance of interferon-based therapy. promacta should be used only in patients with chronic hepatitis c whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. - promacta is indicated in combination with standard immunosuppressive therapy (ist) for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia. - promacta is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. - promacta is not indicated for the treatment of patients with myelodysplastic syndromes (mds) [see warnings and precautions (5.3)] . - safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis c infection. none. risk summary available data from a small number of published case reports and postmarketing experience with promacta use in pregnant women are insufficient to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction and developmental toxicity studies, oral administration of eltrombopag to pregnant rats during organogenesis resulted in embryolethality and reduced fetal weights at maternally toxic doses. these effects were observed at doses resulting in exposures that were six times the human clinical exposure based on area under the curve (auc) in patients with persistent or chronic itp at 75 mg/day, and three times the auc in patients with chronic hepatitis c at 100 mg/day (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 of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data in an early embryonic development study, female rats received oral eltrombopag at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on auc in patients with itp at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on auc in patients with chronic hepatitis c at 100 mg/day). increased pre- and post-implantation loss and reduced fetal weight were observed at the highest dose which also caused maternal toxicity. in an embryo-fetal development study eltrombopag was administered orally to pregnant rats during the period of organogenesis at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on auc in patients with itp at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on auc in patients with chronic hepatitis c at 100 mg/day). decreased fetal weights (6% to 7%) and a slight increase in the presence of cervical ribs were observed at the highest dose which also caused maternal toxicity. however, no evidence of major structural malformations was observed. in an embryo-fetal development study eltrombopag was administered orally to pregnant rabbits during the period of organogenesis at doses of 30, 80, or 150 mg/kg/day (0.04, 0.3, and 0.5 times, respectively, the human clinical exposure based on auc in patients with itp at 75 mg/day and 0.02, 0.1, and 0.3 times, respectively, the human clinical exposure based on auc in patients with chronic hepatitis c at 100 mg/day). no evidence of fetotoxicity, embryolethality, or teratogenicity was observed. in a pre- and post-natal developmental toxicity study in pregnant rats (f0), oral eltrombopag was administered from gestation day 6 through lactation day 20. no adverse effects on maternal reproductive function or on the development of the offspring (f1) were observed at doses up to 20 mg/kg/day (2 times the human clinical exposure based on auc in patients with itp at 75 mg/day and similar to the human clinical exposure based on auc in patients with chronic hepatitis c at 100 mg/day). eltrombopag was detected in the plasma of offspring (f1). the plasma concentrations in pups increased with dose following administration of drug to the f0 dams. risk summary there are no data regarding the presence of eltrombopag or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. however, eltrombopag was detected in the pups of lactating rats 10 days postpartum suggesting the potential for transfer during lactation. due to the potential for serious adverse reactions in a breastfed child from promacta, breastfeeding is not recommended during treatment. contraception based on animal reproduction studies, promacta can cause fetal harm when administered to a pregnant woman. sexually-active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) when using promacta during treatment and for at least 7 days after stopping treatment with promacta. the safety and efficacy of promacta have been established in pediatric patients 1 year and older with persistent or chronic itp and in pediatric patients 2 years and older with ist-naïve severe aplastic anemia (in combination with h-atg and cyclosporine). safety and efficacy in pediatric patients below the age of 1 year with itp have not been established. safety and efficacy in pediatric patients with thrombocytopenia associated with chronic hepatitis c and refractory severe aplastic anemia have not been established. the safety and efficacy of promacta in pediatric patients 1 year and older with persistent or chronic itp were evaluated in two double-blind, placebo-controlled trials [see adverse reactions (6.1), clinical studies (14.1)] . the pharmacokinetics of eltrombopag have been evaluated in 168 pediatric patients 1 year and older with itp dosed once daily [see clinical pharmacology (12.3)] . see dosage and administration (2.1) for dosing recommendations for pediatric patients 1 year and older. the safety and efficacy of promacta in combination with h-atg and cyclosporine for the first-line treatment of severe aplastic anemia in pediatric patients 2 years and older were evaluated in a single-arm, open-label trial [see adverse reactions (6.1), clinical studies (14.3)] . a total of 26 pediatric patients (ages 2 to < 17 years) were evaluated; 12 children (aged 2 to < 12 years) and 14 adolescents (aged 12 to < 17). see dosage and administration (2.3) for dosing recommendations for pediatric patients 2 years and older. the safety and efficacy of promacta in combination with h-atg and cyclosporine in pediatric patients younger than 2 years for the first-line treatment of severe aplastic anemia have not yet been established. in patients 2 to 16 years of age, 69% of patients experienced serious adverse events compared to 42% in patients 17 years and older. among the 12 patients who were 2 to 11 years of age in the promacta d1-m6 cohort and reached the 6-month assessment or withdrew earlier, the complete response rate at month 6 was 8% versus 46% in patients age 12 to 16 years and 50% in patients 17 years of age and older. of the 106 patients in two randomized clinical trials of promacta 50 mg in persistent or chronic itp, 22% were 65 years of age and over, while 9% were 75 years of age and over. of the 1439 patients in two randomized clinical trials of promacta in patients with chronic hepatitis c and thrombocytopenia, 7% were 65 years of age and over, while < 1% were 75 years of age and over. of the 196 patients who received promacta for the treatment of severe aplastic anemia, 18% were 65 years of age and over, while 3% were 75 years of age and over. no overall differences in safety or effectiveness were observed between these patients and younger patients. patients with persistent or chronic itp and severe aplastic anemia reduce the initial dose of promacta in patients with persistent or chronic itp (adult and pediatric patients 6 years and older only) or refractory severe aplastic anemia who also have hepatic impairment (child-pugh class a, b, c) [see dosage and administration (2.1, 2.3), warnings and precautions (5.2), clinical pharmacology (12.3)] . in a clinical trial in patients with severe aplastic anemia who had not received prior definitive immunosuppressive therapy, patients with baseline alt or ast > 5 x uln were ineligible to participate. if a patient with hepatic impairment (child-pugh class a, b, c) initiates therapy with promacta for the first-line treatment of severe aplastic anemia, reduce the initial dose [see dosage and administration (2.3), warnings and precautions (5.2), clinical pharmacology (12.3)] . patients with chronic hepatitis c no dosage adjustment is recommended in patients with chronic hepatitis c and hepatic impairment [see clinical pharmacology (12.3)] . reduce the initial dose of promacta for patients of east-/southeast-asian ancestry with itp (adult and pediatric patients 6 years and older only) or severe aplastic anemia [see dosage and administration (2.1, 2.3), clinical pharmacology (12.3)] . no reduction in the initial dose of promacta is recommended in patients of east-/southeast-asian ancestry with chronic hepatitis c [see clinical pharmacology (12.3)] .

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

rebel distributors corp - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine fumarate 25 mg - seroquel is indicated for the treatment of schizophrenia. the efficacy of seroquel in schizophrenia was established in three 6-week trials in adults and one 6–week trial in adolescents (13–17 years). the effectiveness of seroquel for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [see clinical studies (14.1)] seroquel is indicated for the acute treatment of manic episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10-17 years) [see clinical studies (14.2)]. seroquel is indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. efficacy was established in two 8-week monotherapy trials in adult patients with bipolar i and bipolar ii disorder [see clinical studies (14.2)]. sero

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

contract pharmacy services-pa - levetiracetam (unii: 44yrr34555) (levetiracetam - unii:44yrr34555) - levetiracetam 500 mg - levetiracetam tablets usp are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 1 month of age and older with epilepsy. levetiracetam tablets usp are indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy. levetiracetam tablets usp are indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. levetiracetam is contraindicated in patients with a hypersensitivity to levetiracetam. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.4)] levetiracetam blood levels may decrease during pregnancy [see warnings and precautions ( 5.10)].   pregnancy category c there are no adequate and controlled studies in pregnant women. in animal studies, levetiracetam prod

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

contract pharmacy services-pa - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 500 mg - divalproex sodium extended-release tablets, usp are valproates and are indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. a manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. a mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities). the efficacy of divalproex sodium extended-release tablets, usp are based in part on studies of divalproex sodium delayed-release tablets in this indication, and was confirmed in a 3-week trial with patients meeting dsm-iv tr criteria for bipolar i disorder, manic or mixed type, who were hospitalized for acute mania

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

avpak - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride 75 mg - bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm). the efficacy of bupropion hydrochloride tablets in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with mdd [see clinical studies ( 14)]. - bupropion hydrochloride tablets are contraindicated in patients with a seizure disorder. - bupropion hydrochloride tablets are contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with bupropion hydrochloride tablets [see warnings and precautions ( 5.3)]. - bupropion hydrochloride tablets are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see warnings and precautions ( 5.3) , drug interactions ( 7.3)].  - the use of maois (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride tablets or within 14 days of discontinuing treatment with bupropion hydrochloride tablets are contraindicated. there is an increased risk of hypertensive reactions when bupropion hydrochloride tablets are used concomitantly with maois. the use of bupropion hydrochloride tablets within 14 days of discontinuing treatment with an maoi is also contraindicated. starting bupropion hydrochloride tablets in a patient treated with reversible maois such as linezolid or intravenous methylene blue is contraindicated [see dosage and administration ( 2.4, 2.5), warnings and precautions ( 5.4), drug interactions ( 7.6)] . - bupropion hydrochloride tablets are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride tablets. anaphylactoid/anaphylactic reactions and stevens-johnson syndrome have been reported [see warnings and precautions ( 5.8)].  pregnancy category c risk summary data from epidemiological studies of pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations overall. all pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations, and 15% to 20% for pregnancy loss. no clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (mrhd) and greater and decreased fetal weights were seen at doses twice the mrhd and greater. bupropion hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. clinical considerations consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. human data data from the international bupropion pregnancy registry (675 first-trimester exposures) and a retrospective cohort study using the united healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. the prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international pregnancy registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). data from the united healthcare database and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) from the national birth defects prevention study (nbdps) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (lvoto) are inconsistent and do not allow conclusions regarding a possible association. the united healthcare database lacked sufficient power to evaluate this association; the nbdps found increased risk for lvoto (n = 10; adjusted or = 2.6; 95% ci: 1.2, 5.7), and the slone epidemiology case control study did not find increased risk for lvoto. study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (vsd) are inconsistent and do not allow conclusions regarding a possible association. the slone epidemiology study found an increased risk for vsd following first trimester maternal bupropion exposure (n = 17; adjusted or = 2.5; 95% ci: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including lvoto as above). the nbdps and united healthcare database study did not find an association between first trimester maternal bupropion exposure and vsd. for the findings of lvoto and vsd, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. animal data in studies conducted in rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg per kg per day, respectively (approximately 11 and 7 times the mrhd, respectively, on a mg per m 2 basis). no clear evidence of teratogenic activity was found in either species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg per kg per day, approximately equal to the mrhd on a mg per m 2 basis) and greater. decreased fetal weights were observed at 50 mg per kg and greater. when rats were administered bupropion at oral doses of up to 300 mg per kg per day (approximately 7 times the mrhd on a mg per m 2 basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse effects on offspring development. bupropion and its metabolites are present in human milk. in a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. the average daily infant exposure (assuming 150 ml per kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. exercise caution when bupropion hydrochloride tablets are administered to a nursing woman. safety and effectiveness in the pediatric population have not been established [see boxed warning, warnings and precautions ( 5.1)] . of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. in addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). no overall differences in safety or effectiveness were observed between these subjects and younger subjects. reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. the risk of adverse reactions may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see dosage and administration ( 2.3), use in specific populations (8.6),  clinical pharmacology ( 12.3)] . consider a reduced dose and/or dosing frequency of bupropion hydrochloride tablets in patients with renal impairment (glomerular filtration rate: less than 90 ml per min). bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see dosage and administration ( 2.3), clinical pharmacology ( 12.3)] . in patients with moderate to severe hepatic impairment (child-pugh score: 7 to 15), the maximum dose of bupropion hydrochloride tablets is 75 mg daily. in patients with mild hepatic impairment (child-pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see dosage and administration ( 2.2), clinical pharmacology ( 12.3)] . bupropion is not a controlled substance. humans controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity. in a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like activity as compared with placebo on the morphine-benzedrine subscale of the addiction research center inventories (arci) and a score greater than placebo but less than 15 mg of the schedule ii stimulant dextroamphetamine on the liking scale of the arci. these scales measure general feelings of euphoria and drug liking which are often associated with abuse potential. findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. nonetheless, evidence from single-dose trials does suggest that the recommended daily dosage of bupropion when administered orally in divided doses is not likely to be significantly reinforcing to amphetamine or cns stimulant abusers. however, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse cns stimulant drugs. bupropion hydrochloride tablets are intended for oral use only. the inhalation of crushed tablets or injection of dissolved bupropion has been reported. seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. animals studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. in rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavior response, and increase rates of responding in several schedule-controlled behavior paradigms. in primate models assessing the positive-reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. in rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

avpak - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole 20 mg - 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 includ