Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - efavirenz (unii: je6h2o27p8) (efavirenz - unii:je6h2o27p8) - efavirenz 600 mg - efavirenz in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (hiv-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg. - efavirenz is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., stevens-johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. - coadministration of efavirenz with elbasvir and grazoprevir is contraindicated [see warnings and precautions (5.1) and drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to efavirenz during pregnancy. physicians are encouraged to register patients by calling the antiretroviral pregnancy registry at 1-800-258-4263. risk summary there are retrospective case reports of neural tube defects in infants whose mothers were exposed to efavirenz-containing regimens in the first trimester of pregnancy. prospective pregnancy data from the antiretroviral pregnancy registry are not sufficient to adequately assess this risk. available data from the antiretroviral pregnancy registry show no difference in the risk of overall major birth defects compared to the background rate for major birth defects of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program (macdp). although a causal relationship has not been established between exposure to efavirenz in the first trimester and neural tube defects, similar malformations have been observed in studies conducted in monkeys at doses similar to the human dose. in addition, fetal and embryonic toxicities occurred in rats, at a dose ten times less than the human exposure at recommended clinical dose. because of the potential risk of neural tube defects, efavirenz should not be used in the first trimester of pregnancy. advise pregnant women of the potential risk to a fetus. data human data there are retrospective postmarketing reports of findings consistent with neural tube defects, including meningomyelocele, all in infants of mothers exposed to efavirenz-containing regimens in the first trimester. based on prospective reports from the antiretroviral pregnancy registry (apr) of approximately 1000 live births following exposure to efavirenz-containing regimens (including over 800 live births exposed in the first trimester), there was no difference between efavirenz and overall birth defects compared with the background birth defect rate of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program. as of the interim apr report issued december 2014, the prevalence of birth defects following first-trimester exposure was 2.3% (95% ci: 1.4%-3.6%). one of these prospectively reported defects with first-trimester exposure was a neural tube defect. a single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported. this case also included severe oblique facial clefts and amniotic banding, which have a known association with anophthalmia. animal data effects of efavirenz on embryo-fetal development have been studied in three nonclinical species (cynomolgus monkeys, rats, and rabbits). in monkeys, efavirenz 60 mg/kg/day was administered to pregnant females throughout pregnancy (gestation days 20 through 150). the maternal systemic drug exposures (auc) were 1.3 times the exposure in humans at the recommended clinical dose (600 mg/day), with fetal umbilical venous drug concentrations approximately 0.7 times the maternal values. three of 20 fetuses/infants had one or more malformations; there were no malformed fetuses or infants from placebo-treated mothers. the malformations that occurred in these three monkey fetuses included anencephaly and unilateral anophthalmia in one fetus, microphthalmia in a second, and cleft palate in the third. there was no noael (no observable adverse effect level) established for this study because only one dosage was evaluated. in rats, efavirenz was administered either during organogenesis (gestation days 7 to 18) or from gestation day 7 through lactation day 21 at 50, 100, or 200 mg/kg/day. administration of 200 mg/kg/day in rats was associated with increase in the incidence of early resorptions; and doses 100 mg/kg/day and greater were associated with early neonatal mortality. the auc at the noael (50 mg/kg/day) in this rat study was 0.1 times that in humans at the recommended clinical dose. drug concentrations in the milk on lactation day 10 were approximately 8 times higher than those in maternal plasma. in pregnant rabbits, efavirenz was neither embryo lethal nor teratogenic when administered at doses of 25, 50, and 75 mg/kg/day over the period of organogenesis (gestation days 6 through 18). the auc at the noael (75 mg/kg/day) in rabbits was 0.4 times that in humans at the recommended clinical dose. risk summary the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv. because of the potential for hiv transmission in breastfed infants, advise women not to breastfeed. because of potential teratogenic effects, pregnancy should be avoided in women receiving efavirenz [see use in specific populations (8.1)]. pregnancy testing females of reproductive potential should undergo pregnancy testing before initiation of efavirenz. contraception females of reproductive potential should use effective contraception during treatment with efavirenz and for 12 weeks after discontinuing efavirenz due to the long half-life of efavirenz. barrier contraception should always be used in combination with other methods of contraception. hormonal methods that contain progesterone may have decreased effectiveness [see drug interactions (7.1)]. the safety, pharmacokinetic profile, and virologic and immunologic responses of efavirenz were evaluated in antiretroviral-naive and -experienced hiv-1 infected pediatric patients 3 months to 21 years of age in three open-label clinical trials [see adverse reactions (6.2), clinical pharmacology (12.3), and clinical studies (14.2)]. the type and frequency of adverse reactions in these trials were generally similar to those of adult patients with the exception of a higher frequency of rash, including a higher frequency of grade 3 or 4 rash, in pediatric patients compared to adults [see warnings and precautions (5.8) and adverse reactions (6.2)]. use of efavirenz in patients younger than 3 months of age or less than 3.5 kg body weight is not recommended because the safety, pharmacokinetics, and antiviral activity of efavirenz have not been evaluated in this age group and there is a risk of developing hiv resistance if efavirenz is underdosed. see dosage and administration (2.2) for dosing recommendations for pediatric patients. clinical studies of efavirenz did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. in general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. efavirenz is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary. patients with mild hepatic impairment may be treated with efavirenz without any adjustment in dose. because of the extensive cytochrome p450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering efavirenz to these patients [see warnings and precautions (5.9) and clinical pharmacology (12.3)].

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - cinacalcet hydrochloride (unii: 1k860wsg25) (cinacalcet - unii:uaz6v7728s) - cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (hpt) in adult patients with chronic kidney disease (ckd) on dialysis [see clinical studies (14.1)]. limitations of use: cinacalcet tablets are not indicated for use in patients with ckd who are not on dialysis because of an increased risk of hypocalcemia [see warnings and precautions (5.1)] cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with parathyroid carcinoma [see clinical studies (14.2)].   cinacalcet tablets are indicated for the treatment of severe hypercalcemia in adult patients with primary hpt who are unable to undergo parathyroidectomy [see clinical studies (14.3)].   cinacalcet tablets treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range [see warnings and precautions (5.1)]. risk summary limited case reports of cinacalcet tablets use in pregnant women are insufficient to inform a drug associated risk of adverse developmenta

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - losartan potassium (unii: 3st302b24a) (losartan - unii:jms50mpo89) - losartan potassium tablets are indicated for the treatment of hypertension in adults and pediatric patients 6 years of age and older, to lower blood pressure. lowering blood pressure lowers the risk of fatal and nonfatal cardiovascular (cv) events, primarily strokes and myocardial infarction. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including losartan. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - solifenacin succinate (unii: kka5dld701) (solifenacin - unii:a8910sqj1u) - solifenacin succinate tablets, 5 mg and 10 mg are indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. solifenacin succinate tablets are contraindicated in patients:   • with urinary retention [see warnings and precautions (5.2)], • with gastric retention [see warnings and precautions (5.3)]. • with uncontrolled narrow-angle glaucoma [see warnings and precautions (5.5)], and • who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in solifenacin succinate tablets. reported adverse reactions have included anaphylaxis and angioedema [see adverse reactions (6.2)].   risk summary there are no studies with the use of solifenacin succinate in pregnant women to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. no adverse developmental outcomes were observed in animal reproduction studies with oral administration of solifenacin succinate to pregnant mice during the period of organogenesis at a dose resulting in 1.2 times the systemic exposure at the maximum recommended human dose (mrhd) of 10 mg/day. however, administration of doses 3.6 times and greater than the mrhd during organogenesis produced maternal toxicity in the pregnant mice and resulted in developmental toxicity and reduced fetal body weights in offspring [see data ] . in the u.s. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data oral administration of 14 c-solifenacin succinate to pregnant mice resulted in the recovery of radiolabel in the fetus indicating that solifenacin-related product can cross the placental barrier. in pregnant mice, administration of solifenacin succinate at a dose of 250 mg/kg/day (7.9 times the systemic exposure at the mrhd of 10 mg), resulted in an increased incidence of cleft palate and increased maternal lethality. administration of solifenacin succinate to pregnant mice during organogenesis at greater than or equal to 3.6 times (100 mg/kg/day and greater) the systemic exposure at the mrhd, resulted in reduced fetal body weights and reduced maternal body weight gain. no embryo-fetal toxicity or teratogenicity was observed in fetuses from pregnant mice treated with solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the mrhd). administration of solifenacin succinate to pregnant rats and rabbits at a dose of 50 mg/kg/day (< 1 times and 1.8 times the systemic exposure at the mrhd, respectively), resulted in no findings of embryo-fetal toxicity. oral pre- and post-natal administration of solifenacin succinate at 100 mg/kg/day (3.6 times the systemic exposure at the mrhd) during the period of organogenesis through weaning, resulted in reduced peripartum and postnatal survival, reduced body weight gain by the pups, and delayed physical development (eye opening and vaginal patency). an increase in the percentage of male offspring was also observed in litters from offspring (f2 generation) exposed to maternal doses of 250 mg/kg/day. there were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected systemic exposure at the mrhd. risk summary there is no information on the presence of solifenacin in human milk, the effects on the breastfed child, or the effects on milk production. solifenacin is present in mouse milk [see data]. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for solifenacin succinate and any potential adverse effects on the breastfed child from solifenacin succinate or from the underlying maternal condition. data animal data oral administration of 14 c-solifenacin succinate to lactating mice resulted in the recovery of radioactivity in maternal milk. lactating female mice orally administered solifenacin succinate at a maternally toxic dose of 100 mg/kg/day (3.6 times the systemic exposure at the mrhd) had increased postpartum pup mortality, pups with reduced body weights, or delays in the onset of reflex and physical development. pups from lactating dams orally administered solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the mrhd) had no discernible adverse findings. the concentrations of solifenacin in animal milk does not necessarily predict the concentration of drug in human milk. the safety and effectiveness of solifenacin succinate tablets have not been established in pediatric patients. in placebo-controlled clinical studies, similar safety and effectiveness were observed between geriatric patients (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger adult patients (1188 patients < 65 years) treated with solifenacin succinate [see clinical pharmacology (12.3)] . solifenacin plasma concentrations are greater in patients with severe renal impairment compared to subjects with normal renal function [see clinical pharmacology (12.3)] . because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate in patients with severe renal impairment (clcr < 30 ml/min/1.73 m2 ) is 5 mg once daily [see dosage and administration (2.2)] . the recommended dose in patients with mild or moderate renal impairment is the same as in patients with normal renal function. solifenacin plasma concentrations are greater in patients with moderate hepatic impairment compared to subjects with normal hepatic function [see clinical pharmacology (12.3)] . because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate in patients with moderate hepatic impairment (child-pugh b) is 5 mg once daily [see dosage and administration (2.3)] and solifenacin succinate is not recommended for use in patients with severe hepatic impairment (child-pugh c). the pharmacokinetics of solifenacin is not significantly influenced by gender.

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - oxybutynin chloride (unii: l9f3d9renq) (oxybutynin - unii:k9p6mc7092) - oxybutynin chloride tablets are indicated for the relief of symptoms of bladder instability associated with voiding in patients with uninhibited neurogenic or reflex neurogenic bladder (i.e., urgency, frequency, urinary leakage, urge incontinence, dysuria). oxybutynin chloride is contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. oxybutynin chloride is also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - nateglinide (unii: 41x3pwk4o2) (nateglinide - unii:41x3pwk4o2) - nateglinide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use: nateglinide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. nateglinide tablets are contraindicated in patients with a history of hypersensitivity to nateglinide or its inactive ingredients. risk summary the available data from published literature and the applicant's pharmacovigilance with use of nateglinide in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see clinical considerations ). nateglinide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. in animal reproduction studies, there was no teratogenicity in rats and rabbits administered oral nateglinid

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - amlodipine/valsartan/hydrochlorothiazide is indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine, hydrochlorothiazide, and the arb class to which valsartan principally belongs. there are no controlled trials demonstrating risk reduction with amlodipine/valsartan/hydrochlorothiazide. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education p

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - amlodipine (unii: 1j444qc288) (amlodipine - unii:1j444qc288), valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i) - amlodipine and valsartan is indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including amlodipine and the angiotensin ii receptor blocker (arb) class to which valsartan principally belongs. there are no controlled trials demonstrating risk reduction with amlodipine and valsartan. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint natio

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - valganciclovir hydrochloride (unii: 4p3t9qf9nz) (ganciclovir - unii:p9g3ckz4p5) - treatment of cytomegalovirus (cmv) retinitis : valganciclovir tablets are indicated for the treatment of cmv retinitis in patients with acquired immunodeficiency syndrome (aids) [see clinical studies (14.1) ]. prevention of cmv disease : valganciclovir tablets are indicated for the prevention of cmv disease in kidney, heart, and kidney-pancreas transplant patients at high risk (donor cmv seropositive/recipient cmv seronegative [d+/r-]) [see clinical studies (14.1) ]. prevention of cmv disease : valganciclovir tablets are indicated for the prevention of cmv disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk [see clinical studies (14.2) ]. valganciclovir is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation [see adverse reactions (6.1)].   risk summary after oral administration, valganciclovir (prodrug) is converted to ganciclovir (active drug) and, therefore, valganciclovir is expected to have reproductive toxicity effects similar to ganciclovir. in animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures two-times the human exposure. there are no available human data on use of valganciclovir or ganciclovir in pregnant women to establish the presence or absence of drug-associated risk. the background risk of major birth defects and miscarriage for the indicated populations is unknown. however, the background risk in the u.s. general population of major birth defects is 2-4% and the risk of miscarriage is 15-20% of clinically recognized pregnancies. advise pregnant women of the potential risk to the fetus [see warnings and precautions (5.3), use in specific populations (8.3) ]. clinical considerations disease-associated maternal and/or embryo/fetal risk most maternal cmv infections are asymptomatic or they may be associated with a self-limited mononucleosis-like syndrome. however, in immunocompromised patients (i.e., transplant patients or patients with aids) cmv infections may be symptomatic and may result in significant maternal morbidity and mortality. the transmission of cmv to the fetus is a result of maternal viremia and transplacental infection. perinatal infection can also occur from exposure of the neonate to cmv shedding in the genital tract. approximately 10% of children with congenital cmv infection are symptomatic at birth. mortality in these infants is about 10% and approximately 50-90% of symptomatic surviving newborns experience significant morbidity, including mental retardation, sensorineural hearing loss, microcephaly, seizures, and other medical problems. the risk of congenital cmv infection resulting from primary maternal cmv infection may be higher and of greater severity than that resulting from maternal reactivation of cmv infection. data animal data doses resulting in two-times the human exposure of ganciclovir (based on the human auc following a single intravenous infusion of 5 mg per kg of ganciclovir) resulted in maternal and embryo-fetal toxicity in pregnant mice and rabbits as well as teratogenicity in the rabbits. fetal resorptions were present in at least 85% of rabbits and mice. rabbits showed increased embryo fetal mortality, growth retardation of the fetuses and structural abnormalities of multiple organs of the fetuses including the palate (cleft palate), eyes (anophthalmia/microphthalmia), brain (hydrocephalus), jaw (brachygnathia), kidneys and pancreas (aplastic organs). increased embryo-fetal mortality was also seen in mice. daily intravenous doses of approximately 1.7 times the human exposure (based on auc) administered to female mice prior to mating, during gestation, and during lactation caused hypoplasia of the testes and seminal vesicles in the male offspring, as well as pathologic changes in the nonglandular region of the stomach. data from an ex-vivo human placental model showed that ganciclovir crosses the human placenta. the transfer occurred by passive diffusion and was not saturable over a concentration range of 1 to 10 mg/ml. risk summary  no data are available regarding the presence of valganciclovir (prodrug) or ganciclovir (active drug) in human milk, the effects on the breastfed infant, or the effects on milk production. animal data indicate that ganciclovir is excreted in the milk of lactating rats. the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv. advise nursing mothers that breastfeeding is not recommended during treatment with valganciclovir because of the potential for serious adverse events in nursing infants and because of the potential for transmission of hiv [see boxed warning, warnings and precautions (5.1, 5.3, 5.4, 5.5), nonclinical toxicology (13.1)] . pregnancy testing females of reproductive potential should undergo pregnancy testing before initiation of valganciclovir [see use in specific populations (8.1) ]. contraception females because of the mutagenic and teratogenic potential of valganciclovir, females of reproductive potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with valganciclovir [see dosage and administration (2.6), warnings and precautions (5.4, 5.5), nonclinical toxicology (13.1) ]. males because of its mutagenic potential, males should be advised to use condoms during and for at least 90 days following, treatment with valganciclovir [see dosage and administration (2.6), warnings and precautions (5.3, 5.5), nonclinical toxicology (13.1) ]. infertility : valganciclovir at the recommended doses may cause temporary or permanent female and male infertility [see warnings and precautions (5.3), nonclinical toxicology (13.1) ]. data human data in a small, open-label, non-randomized clinical study, adult male renal transplant patients receiving valganciclovir for cmv prophylaxis for up to 200 days post-transplantation were compared to an untreated control group. patients were followed-up for six months after valganciclovir discontinuation. among 24 evaluable patients in the valganciclovir group, the mean sperm density at the end of treatment visit decreased by 11 million/ml from baseline; whereas, among 14 evaluable patients in the control group the mean sperm density increased by 33 million/ml. however, at the follow-up visit among 20 evaluable patients in the valganciclovir group the mean sperm density was comparable to that observed among 10 evaluable patients in the untreated control group (the mean sperm density at the end of follow-up visit increased by 41 million/ml from baseline in the valganciclovir group and by 43 million/ml in the untreated group). valganciclovir for oral solution and tablets are indicated for the prevention of cmv disease in pediatric kidney transplant patients 4 months to 16 years of age and in pediatric heart transplant patients 1 month to 16 years of age at risk for developing cmv disease [see indications and usage (1.2), dosage and administration (2.3) ]. the use of valganciclovir for oral solution and tablets for the prevention of cmv disease in pediatric kidney transplant patients 4 months to 16 years of age is based on two single-arm, open-label, non-comparative studies in patients 4 months to 16 years of age. study 1 was a safety and pharmacokinetic study in pediatric solid organ transplant patients (kidney, liver, heart, and kidney/pancreas). valganciclovir was administered once daily within 10 days of transplantation for a maximum of 100 days post-transplantation. study 2 was a safety and tolerability study where valganciclovir was administered once daily within 10 days of transplantation for a maximum of 200 days post-transplantation in pediatric kidney transplant patients. the results of these studies were supported by previous demonstration of efficacy in adult patients [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2) ]. the use of valganciclovir for oral solution and tablets for the prevention of cmv disease in pediatric heart transplant patients 1 month to 16 years of age is based on two studies (study 1 described above and study 3) and was supported by previous demonstration of efficacy in adult patients [see clinical pharmacology (12.3), clinical studies (14.2) ]. study 3 was a pharmacokinetic and safety study of valganciclovir in pediatric heart transplant patients less than 4 months of age who received a single dose of valganciclovir oral solution on each of two consecutive days. a physiologically based pharmacokinetic (pbpk) model was developed based on the available pharmacokinetic data from pediatric and adult patients to support dosing in heart transplant patients less than 1 month of age. however, due to uncertainty in model predictions for neonates, valganciclovir is not indicated for prophylaxis in this age group. the safety and efficacy of valganciclovir for oral solution and tablets have not been established in children for prevention of cmv disease in pediatric liver transplant patients, in kidney transplant patients less than 4 months of age, in heart transplant patients less than 1 month of age, in pediatric aids patients with cmv retinitis, and in infants with congenital cmv infection. a pharmacokinetic and pharmacodynamic evaluation of valganciclovir for oral solution was performed in 24 neonates with congenital cmv infection involving the central nervous system. all patients were treated for 6 weeks with a combination of intravenous ganciclovir 6 mg per kg twice daily or valganciclovir for oral solution at doses ranging from 14 mg per kg to 20 mg per kg twice daily. the pharmacokinetic results showed that in infants greater than 7 days to 3 months of age, a dose of 16 mg per kg twice daily of valganciclovir for oral solution provided ganciclovir systemic exposures (median auc0-12h = 23.6 [range 16.8-35.5] mcg·h/ml; n = 6) comparable to those obtained in infants up to 3 months of age from a 6 mg per kg dose of intravenous ganciclovir twice daily (auc0-12h = 25.3 [range 2.4-89.7] mcg·h/ml; n = 18) or to the ganciclovir systemic exposures obtained in adults from a 900 mg dose of valganciclovir tablets twice daily. however, the efficacy and safety of intravenous ganciclovir and of valganciclovir have not been established for the treatment of congenital cmv infection in infants and no similar disease occurs in adults; therefore, efficacy cannot be extrapolated from intravenous ganciclovir use in adults. studies of valganciclovir tablets have not been conducted in adults older than 65 years of age. clinical studies of valganciclovir did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. valganciclovir is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because renal clearance decreases with age, valganciclovir should be administered with consideration of their renal status. renal function should be monitored and dosage adjustments should be made accordingly [see dosage and administration (2.5), warnings and precautions (5.2), use in specific populations (8.6), clinical pharmacology (12.3) ]. dose reduction is recommended when administering valganciclovir to patients with renal impairment [see dosage and administration (2.5), warnings and precautions (5.2), clinical pharmacology (12.3) ]. for adult patients on hemodialysis (crcl less than10 ml/min), valganciclovir tablets should not be used. adult hemodialysis patients should use ganciclovir in accordance with the dose-reduction algorithm cited in the cytovene® -iv complete product information section on dosage and administration: renal impairment [see dosage and administration (2.5) and clinical pharmacology (12.3) ]. the safety and efficacy of valganciclovir have not been studied in patients with hepatic impairment.

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

strides pharma science limited - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9), sodium bicarbonate (unii: 8mdf5v39qo) (bicarbonate ion - unii:hn1zra3q20) - omeprazole and sodium bicarbonate for oral suspension is indicated in adults for the: - short-term treatment of active duodenal ulcer. most patients heal within four weeks. some patients may require an additional four weeks of therapy. - short-term treatment (4 to 8 weeks) of active benign gastric ulcer. - treatment of heartburn and other symptoms associated with gerd for up to 4 weeks. - short-term treatment (4 to 8 weeks) of ee due to acid-mediated gerd which has been diagnosed by endoscopy in adults. the efficacy of omeprazole and sodium bicarbonate for oral suspension used for longer than 8 weeks in patients with ee has not been established. if a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. if there is recurrence of ee or gerd symptoms (e.g., heartburn), additional 4 to 8-week courses of omeprazole and sodium bicarbonate for oral suspension may be considered. - the efficacy of omeprazole and sodium bicarbonate for oral suspension used for longer than 8 weeks in patients with ee has not been established. if a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. if there is recurrence of ee or gerd symptoms (e.g., heartburn), additional 4 to 8-week courses of omeprazole and sodium bicarbonate for oral suspension may be considered. - maintenance of healing of ee due to acid-mediated gerd. controlled studies do not extend beyond 12 months. omeprazole and sodium bicarbonate for oral suspension is indicated in adults for the : - reduction of risk of upper gi bleeding in critically ill adult patients. omeprazole and sodium bicarbonate is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2), adverse reactions (6.2)]. proton pump inhibitors (ppis), including omeprazole and sodium bicarbonate, are contraindicated in patients receiving rilpivirine containing products [see drug interactions (7)]. risk summary there are no adequate and well-controlled studies with omeprazole and sodium bicarbonate for oral suspension in pregnant women. omeprazole and sodium bicarbonate for oral suspension contains omeprazole and sodium bicarbonate. omeprazole there are no adequate and well-controlled studies with omeprazole in pregnant women. available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person). changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age (see data ). sodium bicarbonate available data with sodium bicarbonate use in pregnant women are insufficient to identify a drug associated risk of major birth defects or miscarriage. published animal studies report that sodium bicarbonate administered to rats, mice or rabbits during pregnancy did not cause adverse developmental effects in offspring. the estimated background risks of major birth defects and miscarriage for the indicated population are 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 human data there are no adequate and well-controlled studies with omeprazole and sodium bicarbonate in pregnant women. four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to h2 -receptor antagonists or other controls. a population-based retrospective cohort epidemiological study from the swedish medical birth register, covering approximately 99% of pregnancies, from 1995-99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. the number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low apgar score, or hospitalization was similar to the number observed in this population. the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. a population-based retrospective cohort study covering all live births in denmark from 1996-2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any ppi. the overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any ppi during the first trimester. a retrospective cohort study reported on 689 pregnant women exposed to either h2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. the overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an h2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1%, respectively. a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% first trimester exposures). the reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. several studies have reported no apparent adverse short-term effects on the infant when single-dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. animal data omeprazole reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. in rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. in rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. esomeprazole the data described below was generated from studies using esomeprazole, an enantiomer of omeprazole. the animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human dose of 40 mg of esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development were performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg of esomeprazole or 40 mg omeprazole on a body surface area basis). neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). in addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses of esomeprazole magnesium equal to or greater than 14 mg/kg/day (about 3.4 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). when rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses of esomeprazole magnesium equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). a pre- and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. a follow-up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. risk summary available data from the published literature suggest both components of omeprazole and sodium bicarbonate for oral suspension, omeprazole and sodium bicarbonate, are present in human milk. there are no clinical data on the effects of omeprazole or sodium bicarbonate on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omeprazole and sodium bicarbonate and any potential adverse effects on the breastfed infant from omeprazole and sodium bicarbonate or from the underlying maternal condition. safety and effectiveness of omeprazole and sodium bicarbonate for oral suspension have not been established in pediatric patients. juvenile animal data esomeprazole, an enantiomer of omeprazole, was shown to decrease body weight, body weight gain, femur weight, femur length, and overall growth at oral doses about 34 to 68 times a daily human dose of 40 mg esomeprazole or 40 mg omeprazole based on body surface area in a juvenile rat toxicity study. the animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. a 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with esomeprazole magnesium at doses of 70 to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). an increase in the number of deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered esomeprazole magnesium from postnatal day 7 through postnatal day 35. in addition, doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis), produced treatment-related decreases in body weight (approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected overall growth. comparable findings described above have also been observed in this study with another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole. omeprazole was administered to over 2,000 elderly individuals (≥65 years of age) in clinical trials in the u.s. and europe. there were no differences in safety and effectiveness between the elderly and younger subjects. other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. pharmacokinetic studies with buffered omeprazole have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. the plasma clearance of omeprazole was 250 ml/min (about half that of young subjects). the plasma half-life averaged one hour, about twice that in nonelderly, healthy subjects taking omeprazole and sodium bicarbonate for oral suspension. however, no dosage adjustment is necessary in the elderly [see clinical pharmacology (12.3)]. in patients with hepatic impairment (child-pugh class a, b, or c) exposure to omeprazole substantially increased compared to healthy subjects. avoid use of omeprazole and sodium bicarbonate in patients with hepatic impairment for maintenance of healing of erosive esophagitis [see clinical pharmacology (12.3)]. in studies of healthy subjects, asians had approximately a four-fold higher exposure than caucasians. avoid use of omeprazole and sodium bicarbonate in asian patients for maintenance of healing of erosive esophagitis [see clinical pharmacology (12.5)].