United States - English - NLM (National Library of Medicine)

bayer healthcare llc - antihemophilic factor, human recombinant (unii: p89dr4ny54) (antihemophilic factor, human recombinant - unii:p89dr4ny54) - antihemophilic factor, human recombinant 1000 [iu] in 2.5 ml - kogenate® fs is a recombinant antihemophilic factor indicated for: kogenate fs is not indicated for the treatment of von willebrand disease. kogenate fs is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis to mouse or hamster protein or other constituents of the product (sucrose, glycine, histidine, sodium, calcium chloride, polysorbate 80, imidazole, tri-n-butyl phosphate, and copper). there are no data with kogenate fs use in pregnant women to inform on drug-associated risk. animal reproduction studies have not been conducted with kogenate fs. it is also not known whether kogenate fs can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. there is no information regarding the presence of kogenate fs in human milk, the effects on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for kogenate fs and any potential adverse effects on the breastfed child from kogenate fs or from the underlying maternal condition. safety and efficacy studies have been performed in previously untreated and minimally treated pediatric patients. children, in comparison to adults, present higher factor viii clearance values and, thus, lower half-life and recovery of factor viii. this may be due to differences in body composition.13 account for this difference in clearance when dosing or following factor viii levels in the pediatric population [see clinical pharmacology (12.3)] . routine prophylactic treatment in children ages 0–2.5 years with no pre-existing joint damage has been shown to reduce spontaneous joint bleeding and the risk of joint damage. this data can be extrapolated to ages >2.5–16 years for children who have no existing joint damage [see clinical studies (14)] . clinical studies with kogenate fs did not include patients aged 65 and over. dose selection for an elderly patient should be individualized.

United States - English - NLM (National Library of Medicine)

american health packaging - tizanidine hydrochloride (unii: b53e3nmy5c) (tizanidine - unii:6ai06c00gw) - tizanidine 2 mg - tizanidine tablet is a central alpha-2-adrenergic agonist indicated for the management of spasticity. because of the short duration of therapeutic effect, treatment with tizanidine tablets should be reserved for those daily activities and times when relief of spasticity is most important [see dosage and administration (2.1)]. tizanidine hydrochloride is contraindicated in patients taking potent inhibitors of cyp1a2, such as fluvoxamine or ciprofloxacin [see drug interactions (7.1, 7.2)]. pregnancy category c tizanidine hydrochloride has not been studied in pregnant women. tizanidine hydrochloride should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m 2 basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m 2 basis, did not show evidence of teratogenicity. tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m 2 basis increased gestation duration in rats. prenatal and postnatal pup loss was increased and developmental retardation occurred. post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m 2 basis. it is not known whether this drug is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when tizanidine hydrochloride is administered to a nursing woman. safety and effectiveness in pediatric patients have not been established. tizanidine hydrochloride is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. clinical studies of tizanidine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. cross-study comparison of pharmacokinetic data following single dose administration of 6 mg tizanidine hydrochloride showed that younger subjects cleared the drug four times faster than the elderly subjects. in elderly patients with renal insufficiency (creatinine clearance <25 ml/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. during titration, the individual doses should be reduced. if higher doses are required, individual doses rather than dosing frequency should be increased. monitor elderly patients because they may have an increased risk for adverse reactions associated with tizanidine hydrochloride. tizanidine hydrochloride is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. in patients with renal insufficiency (creatinine clearance < 25 ml/min) clearance was reduced by more than 50%. in these patients, during titration, the individual doses should be reduced. if higher doses are required, individual doses rather than dosing frequency should be increased. these patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [see dosage and administration (2.2), warnings and precautions (5.7) and clinical pharmacology (12.3)] the influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. [see dosing and administration (2.3), warnings and precautions (5.2), and clinical pharmacology (12.3)]. abuse potential was not evaluated in human studies. rats were able to distinguish tizanidine from saline in a standard discrimination paradigm, after training, but failed to generalize the effects of morphine, cocaine, diazepam, or phenobarbital to tizanidine. tizanidine is closely related to clonidine, which is often abused in combination with narcotics and is known to cause symptoms of rebound upon abrupt withdrawal. three cases of rebound symptoms on sudden withdrawal of tizanidine have been reported. the case reports suggest that these patients were also misusing narcotics. withdrawal symptoms included hypertension, tachycardia, hypertonia, tremor, and anxiety. withdrawal symptoms are more likely to occur in cases where high doses are used, especially for prolonged periods, or with concomitant use of narcotics. if therapy needs to be discontinued, the dose should be decreased slowly to minimize the risk of withdrawal symptoms [see dosage and administration (2.2)]. monkeys were shown to self-administer tizanidine in a dose-dependent manner, and abrupt cessation of tizanidine produced transient signs of withdrawal at doses > 35 times the maximum recommended human dose on a mg/m 2 basis. these transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.

United States - English - NLM (National Library of Medicine)

sanofi pasteur inc. - influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) antigen (formaldehyde inactivated) (unii: xw4jb03ti5) (influenza a virus a/brisbane/02/2018 ivr-190 (h1n1) hemagglutinin antigen (formaldehyde inactivated) - unii:92xe6ghc89), influenza a virus a/kansas/14/2017 x-327 (h3n2) antigen (formaldehyde inactivated) (unii: 3nzw5nd3d6) (influenza a virus a/kansas/14/2017 x-327 (h3n2) hemagglutinin antigen (formaldehyde inactivated) - unii:k329ycd1n9), influenza b virus b/maryland/15/2016 bx-69a antigen (formaldeh - influenza a virus a/michigan/45/2015 x-275 (h1n1) hemagglutinin antigen (formaldehyde inactivated) 60 ug in 0.5 ml - fluzone® high-dose is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza a subtype viruses and type b virus contained in the vaccine. fluzone high-dose is approved for use in persons 65 years of age and older. a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see description (11) ], including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of fluzone high-dose. fluzone high-dose is not approved for use in persons <65 years of age. there are limited human data and no animal data available to establish whether there is a vaccine-associated risk with use of fluzone high-dose in pregnancy. fluzone high-dose is not approved for use in persons <65 years of age. no human or animal data are available to assess the effects of fluzone high-dose on the breastfed infant or on milk production/excretion. safety and effectiveness of fluzone high-dose in persons <65 years of age have not bee

United States - English - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - hydrocortisone (unii: wi4x0x7bpj) (hydrocortisone - unii:wi4x0x7bpj) - hydrocortisone 1 mg in 1 g - hydrocortisone butyrate cream, 0.1% (lipophilic) is indicated for: none. there are no adequate and well-controlled studies in pregnant women. therefore, hydrocortisone butyrate cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. note: the animal multiples of human exposure calculations in this label were based on body surface area comparisons for an adult (i.e., mg/m2 /day dose comparisons) assuming 100% human percutaneous absorption of a maximum topical human dose (mthd) for hydrocortisone butyrate cream (25 g). systemic embryofetal development studies were conducted in rats and rabbits. subcutaneous doses of 0.6, 1.8 and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 6 to 17. in the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day (2x mthd) included an increased incidence of ossification variations and unossified sternebra. no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 5.4 and 1.8 mg/kg/day, respectively (2x mthd and 0.7x mthd, respectively). subcutaneous doses of 0.1, 0.2 and 0.3 mg/kg/day hydrocortisone butyrate were administered to pregnant female rabbits during gestation days 7 to 20. an increased incidence of abortion was noted at 0.3 mg/kg/day (0.2x mthd). in the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day (0.1x mthd). additional indicators of embryofetal toxicity (reduction in litter size, decreased number of viable fetuses, increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day (0.2x mthd). additional fetal effects noted in this study included delayed ossification noted at doses ≥0.1 mg/kg/day and an increased incidence of fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. a dose at which no treatment-related effects on embryofetal toxicity or teratogenicity were observed was not established in this study. additional systemic embryofetal development studies were conducted in rats and mice. subcutaneous doses of 0.1 and 9 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 9 to 15. in the presence of maternal toxicity, an increase in fetal deaths and fetal resorptions and an increase in the number of ossifications in caudal vertebrae were noted at a dose of 9 mg/kg/day (3x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at 0.1 mg/kg/day (0.1x mthd). subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 to 13. in the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at a dose of 1 mg/kg/day (0.2x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 1 and 0.2 mg/kg/day, respectively (0.2x mthd and 0.1x mthd, respectively). no topical embryofetal development studies were conducted with hydrocortisone butyrate cream. however, topical embryofetal development studies were conducted in rats and rabbits with a hydrocortisone butyrate ointment formulation. topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days 6 to 15 or pregnant female rabbits during gestation days 6 to 18. a dose-dependent increase in fetal resorptions was noted in rabbits (0.2 to 2x mthd) and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate ointment dose (80x mthd). no treatment-related effects on embryofetal toxicity were noted at the 1% hydrocortisone butyrate ointment dose in rats (8x mthd). a dose at which no treatment-related effects on embryofetal toxicity were observed in rabbits after topical administration of hydrocortisone butyrate ointment was not established in this study. no treatment-related effects on teratogenicity were noted at a dose of 10% hydrocortisone butyrate ointment in rats or rabbits (80x mthd and 2x mthd, respectively). a peri- and post-natal development study was conducted in rats. subcutaneous doses of 0.6, 1.8 and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats from gestation day 6 to lactation day 20. in the presence of maternal toxicity, a dose-dependent decrease in fetal weight was noted at doses ≥1.8 mg/kg/day (0.7x mthd). no treatment-related effects on fetal toxicity were noted at 0.6 mg/kg/day (0.2x mthd). a delay in sexual maturation was noted at 5.4 mg/kg/day (2x mthd). no treatment-related effects on sexual maturation were noted at 1.8 mg/kg/day. no treatment-related effects on behavioral development or subsequent reproductive performance were noted at 5.4 mg/kg/day. systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. it is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. because many drugs are excreted in human milk, caution should be exercised when hydrocortisone butyrate cream is administered to a nursing woman. safety and efficacy in pediatric patients below 3 months of age have not been established. because of higher skin surface-to-body-mass ratios, pediatric patients are at a greater risk than adults of hpa axis suppression when they are treated with topical corticosteroids [see warnings and precautions (5.1)] . they are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of cushing’s syndrome while on treatment. eighty-six (86) pediatric subjects (between 5 months and 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (bsa) treated with hydrocortisone butyrate cream three times daily for up to 4 weeks were assessed for hpa axis suppression in two separate studies. the disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in these hpa axis studies were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (two times daily) for which hydrocortisone butyrate cream is indicated in this population. five of the 82 evaluable subjects (6.1%) demonstrated evidence of suppression, where the criterion for defining hpa axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter after cosyntropin stimulation. suppressed subjects ranged in age from 5 months to 16 years and, at the time of enrollment, had 25% to 95% bsa involvement. these subjects did not demonstrate any clinical signs or symptoms despite evidence of hpa axis suppression. at the first follow up visit, approximately one month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. this last subject recovered adrenal function by 65 days post-treatment. cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have also been reported in pediatric patients receiving topical corticosteroids. manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to acth stimulation. manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. clinical studies of hydrocortisone butyrate cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

United States - English - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - fluocinonide (unii: 2w4a77ypan) (fluocinonide - unii:2w4a77ypan) - fluocinonide cream usp, 0.1% is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses in patients 12 years of age or older [see use in specific populations (8.4) ]. treatment beyond 2 consecutive weeks is not recommended and the total dosage should not exceed 60 g per week because the safety of fluocinonide cream usp, 0.1% for longer than 2 weeks has not been established and because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (hpa) axis. therapy should be discontinued when control of the disease is achieved. if no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. do not use more than half of the 120 g tube per week. fluocinonide cream usp, 0.1% should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae. none. teratogenic effects: pregnancy category c there are no adequate and well-controlled studies in pregnant women. therefore, fluocinonide cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. it is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. nevertheless, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. safety and efficacy of fluocinonide cream in pediatric patients younger than 12 years of age have not been established; therefore use in pediatric patients younger than 12 years of age is not recommended. hpa axis suppression was studied in 4 sequential cohorts of pediatric patients with atopic dermatitis covering at least 20% of the body surface area, treated once daily or twice daily with fluocinonide cream. the first cohort of 31 patients (mean 36.3% bsa) 12 to < 18 years old; the second cohort included 31 patients (mean 39.0% bsa) 6 to < 12 years old; the third cohort included 30 patients (mean 34.6% bsa) 2 to < 6 years old; the fourth cohort included 31 patients (mean 40.0% bsa) 3 months to < 2 years old. fluocinonide cream caused hpa-axis suppression in 1 patient in the twice daily group in cohort 1, 2 patients in the twice daily group in cohort 2, and 1 patient in the twice daily group in cohort 3. follow-up testing 14 days after treatment discontinuation, available for all 4 suppressed patients, demonstrated a normally responsive hpa axis. signs of skin atrophy were present at baseline and severity was not determined making it difficult to assess local skin safety. therefore, the safety of fluocinonide cream in patients younger than 12 years of age has not been demonstrated [see warnings and precautions (5.2) ]. hpa axis suppression has not been evaluated in patients with psoriasis who are less than 18 years of age. because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of hpa-axis suppression and cushing’s syndrome when they are treated with topical corticosteroids. they are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. hpa-axis suppression, cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to cosyntropin (acth1-24 ) stimulation. manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. clinical studies of fluocinonide cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

United States - English - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - pimecrolimus (unii: 7kyv510875) (pimecrolimus - unii:7kyv510875) - pimecrolimus cream, 1% is contraindicated in individuals with a history of hypersensitivity to pimecrolimus or any of the components of the cream. pregnancy category c there are no adequate and well-controlled studies with pimecrolimus cream, 1% in pregnant women. therefore, pimecrolimus cream, 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. in dermal embryofetal developmental studies, no maternal or fetal toxicity was observed up to the highest practicable doses tested, 10 mg/kg/day (1% pimecrolimus cream) in rats (0.14x mrhd based on body surface area) and 10 mg/kg/day (1% pimecrolimus cream) in rabbits (0.65x mrhd based on auc comparisons). the 1% pimecrolimus cream was administered topically for 6 hours/day during the period of organogenesis in rats and rabbits (gestational days 6 to 21 in rats and gestational days 6 to 20 in rabbits). a second dermal embryofetal development study was conducted in rats using pimecrolimus cream applied dermally to pregnant rats (1 g cream/kg body weight of 0.2%, 0.6% and 1% pimecrolimus cream) from gestation day 6 to 17 at doses of 2, 6, and 10 mg/kg/day with daily exposure of approximately 22 hours. no maternal, reproductive, or embryo-fetal toxicity attributable to pimecrolimus was noted at 10 mg/kg/day (0.66x mrhd based on auc comparisons), the highest dose evaluated in this study. no teratogenicity was noted in this study at any dose. a combined oral fertility and embryofetal developmental study was conducted in rats and an oral embryofetal developmental study was conducted in rabbits. pimecrolimus was administered during the period of organogenesis (2 weeks prior to mating until gestational day 16 in rats, gestational days 6 to 18 in rabbits) up to dose levels of 45 mg/kg/day in rats and 20 mg/kg/day in rabbits. in the absence of maternal toxicity, indicators of embryofetal toxicity (post-implantation loss and reduction in litter size) were noted at 45 mg/kg/day (38x mrhd based on auc comparisons) in the oral fertility and embryofetal developmental study conducted in rats. no malformations in the fetuses were noted at 45 mg/kg/day (38x mrhd based on auc comparisons) in this study. no maternal toxicity, embryotoxicity or teratogenicity were noted in the oral rabbit embryofetal developmental toxicity study at 20 mg/kg/day (3.9x mrhd based on auc comparisons), which was the highest dose tested in this study. a second oral embryofetal development study was conducted in rats. pimecrolimus was administered during the period of organogenesis (gestational days 6 to 17) at doses of 2, 10 and 45 mg/kg/day. maternal toxicity, embryolethality and fetotoxicity were noted at 45 mg/kg/day (271x mrhd based on auc comparisons). a slight increase in skeletal variations that were indicative of delayed skeletal ossification was also noted at this dose. no maternal toxicity, embryolethality or fetotoxicity were noted at 10 mg/kg/day (16x mrhd based on auc comparisons). no teratogenicity was noted in this study at any dose. a second oral embryofetal development study was conducted in rabbits. pimecrolimus was administered during the period of organogenesis (gestational days 7 to 20) at doses of 2, 6 and 20 mg/kg/day. maternal toxicity, embryotoxicity and fetotoxicity were noted at 20 mg/kg/day (12x mrhd based on auc comparisons). a slight increase in skeletal variations that were indicative of delayed skeletal ossification was also noted at this dose. no maternal toxicity, embryotoxicity or fetotoxicity were noted at 6 mg/kg/day (5x mrhd based on auc comparisons). no teratogenicity was noted in this study at any dose. an oral peri- and post-natal developmental study was conducted in rats. pimecrolimus was administered from gestational day 6 through lactational day 21 up to a dose level of 40 mg/kg/day. only 2 of 22 females delivered live pups at the highest dose of 40 mg/kg/day. postnatal survival, development of the f1 generation, their subsequent maturation and fertility were not affected at 10 mg/kg/day (12x mrhd based on auc comparisons), the highest dose evaluated in this study. pimecrolimus was transferred across the placenta in oral rat and rabbit embryofetal developmental studies. it is not known whether this drug is excreted in human milk. because of the potential for serious adverse reactions in nursing infants from pimecrolimus, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. pimecrolimus cream, 1% is not indicated for use in children less than 2 years of age. the long-term safety and effects of pimecrolimus cream, 1% on the developing immune system are unknown three phase 3 pediatric trials were conducted involving 1,114 subjects 2 to 17 years of age. two trials were 6-week randomized vehicle-controlled trials with a 20-week open-label phase and one was a vehicle-controlled (up to 1 year) safety trial with the option for sequential topical corticosteroid use. of these subjects 542 (49%) were 2 to 6 years of age. in the short-term trials, 11% of pimecrolimus cream, 1% subjects did not complete these trials and 1.5% of pimecrolimus cream, 1%, subjects discontinued due to adverse events. in the one-year trial, 32% of pimecrolimus cream, 1%, subjects did not complete this trial and 3% of pimecrolimus cream, 1%, subjects discontinued due to adverse events. most discontinuations were due to unsatisfactory therapeutic effect. the most common local adverse event in the short-term trials of pimecrolimus cream, 1% in pediatric subjects ages 2 to 17 was application site burning (10% vs. 13% vehicle); the incidence in the long-term trial was 9% pimecrolimus cream, 1% vs. 7% vehicle [see adverse reactions (6.1)]. adverse events that were more frequent (>5%) in subjects treated with pimecrolimus cream, 1% compared to vehicle were headache (14% vs. 9%) in the short-term trial. nasopharyngitis (26% vs. 21%), influenza (13% vs. 4%), pharyngitis (8% vs. 3%), viral infection (7% vs. 1%), pyrexia (13% vs. 5%), cough (16% vs. 11%), and headache (25% vs. 16%) were increased over vehicle in the 1-year safety trial [see adverse reactions (6.1)]. in 843 subjects ages 2 to 17 years treated with pimecrolimus cream, 1%9 (0.8%) developed eczema herpeticum (5 on pimecrolimus cream alone and 4 on pimecrolimus cream, 1% used in sequence with corticosteroids). in 211 subjects on vehicle alone, there were no cases of eczema herpeticum. the majority of adverse events were mild to moderate in severity. two phase 3 trials were conducted involving 436 infants age 3 months to 23 months. one 6-week randomized vehicle-controlled trial with a 20-week open-label phase and one safety trial, up to one year, were conducted. in the 6-week trial, 11% of pimecrolimus cream, 1% and 48% of vehicle subjects did not complete this trial; no subject in either group discontinued due to adverse events. infants on pimecrolimus cream, 1% had an increased incidence of some adverse events compared to vehicle. in the 6-week vehicle-controlled trial these adverse events included pyrexia (32% vs. 13% vehicle), uri (24% vs. 14%), nasopharyngitis (15% vs. 8%), gastroenteritis (7% vs. 3%), otitis media (4% vs. 0%), and diarrhea (8% vs. 0%). in the open-label phase of the trial, for infants who switched to pimecrolimus cream, 1% from vehicle, the incidence of the above-cited adverse events approached or equaled the incidence of those subjects who remained on pimecrolimus cream, 1%. in the 6 month safety data, 16% of pimecrolimus cream, 1% and 35% of vehicle subjects discontinued early and 1.5% of pimecrolimus cream, 1% and 0% of vehicle subjects discontinued due to adverse events. infants on pimecrolimus cream, 1% had a greater incidence of some adverse events as compared to vehicle. these included pyrexia (30% vs. 20%), uri (21% vs. 17%), cough (15% vs. 9%), hypersensitivity (8% vs. 2%), teething (27% vs. 22%), vomiting (9% vs. 4%), rhinitis (13% vs. 9%), viral rash (4% vs. 0%), rhinorrhea (4% vs. 0%), and wheezing (4% vs. 0%). the systemic exposure to pimecrolimus from pimecrolimus cream, 1% was investigated in 28 pediatric subjects with atopic dermatitis (20% to 80% bsa involvement) between the ages of 8 months to 14 yrs. following twice daily application for three weeks, blood concentrations of pimecrolimus were <2 ng/ml with 60% (96/161) of the blood samples having blood concentration below the limit of quantification (0.5 ng/ml). however, more children (23 children out of the total 28 children investigated) had at least one detectable blood level as compared to the adults (12 adults out of the total 52 adults investigated) over a 3-week treatment period. due to the erratic nature of the blood levels observed, no correlation could be made between amount of cream, degree of bsa involvement, and blood concentrations. in general, the blood concentrations measured in adult atopic dermatitis subjects were comparable to those seen in the pediatric population. in a second group of 30 pediatric subjects aged 3 to 23 months with 10% to 92% bsa involvement, following twice daily application for three weeks, blood concentrations of pimecrolimus were <2.6 ng/ml with 65% (75/116) of the blood samples having blood concentration below 0.5ng/ml, and 27% (31/116) below the limit of quantification (0.1 ng/ml) for these trials. overall, a higher proportion of detectable blood levels was seen in the pediatric subject population as compared to adult population. this increase in the absolute number of positive blood levels may be due to the larger surface area to body mass ratio seen in these younger subjects. in addition, a higher incidence of upper respiratory symptoms/infections was also seen relative to the older age group in the pk trials. at this time, a causal relationship between these findings and pimecrolimus cream, 1% use cannot be ruled out. nine (9) subjects ≥65 years old received pimecrolimus cream, 1% in phase 3 trials. clinical trials of pimecrolimus cream, 1% did not include sufficient numbers of subjects aged 65 and over to assess efficacy and safety.

United States - English - NLM (National Library of Medicine)

sanofi pasteur inc. - influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) antigen (formaldehyde inactivated) (unii: au5c98u4bb) (influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) hemagglutinin antigen (formaldehyde inactivated) - unii:c46xjt9fq9), influenza a virus a/darwin/9/2021 san-010 (h3n2) antigen (formaldehyde inactivated) (unii: kja387fhb2) (influenza a virus a/darwin/9/2021 san-010 (h3n2) hemagglutinin antigen (formaldehyde inactivated) - unii:6s4y8a8uey), influenza b virus b/phuket/3073/2013 antigen (formaldehy - fluzone® high-dose quadrivalent is a vaccine indicated for active immunization for the prevention of influenza caused by influenza a subtype viruses and type b viruses contained in the vaccine. fluzone high-dose quadrivalent is indicated for use in persons 65 years of age and older. a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see description (11)] , including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of fluzone high-dose quadrivalent. fluzone high-dose quadrivalent is not approved for use in persons <65 years of age. there are limited human data on fluzone high-dose and no animal data available on fluzone high-dose quadrivalent to establish whether there is a vaccine-associated risk with use of fluzone high-dose quadrivalent in pregnancy. fluzone high-dose quadrivalent is not approved for use in persons <65 years of age. no human or animal data are available to assess the effects of fluzone high-dose quadrivalent on

New Zealand - English - Medsafe (Medicines Safety Authority)

bayer new zealand limited - meglumine amidotrizoate 65%{relative} - solution for injection - 65% w/v - active: meglumine amidotrizoate 65%{relative}

United States - English - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - warfarin sodium (unii: 6153cwm0cl) (warfarin - unii:5q7zvv76ei) - warfarin sodium 1 mg - warfarin sodium tablets are indicated for: - prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (pe). - prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (af) and/or cardiac valve replacement. - reduction in the risk of death, recurrent myocardial infarction (mi), and thromboembolic events such as stroke or systemic embolization after myocardial infarction limitations of use warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. warfarin sodium is contraindicated in: - pregnancy warfarin sodium tablets are contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromb

United States - English - NLM (National Library of Medicine)

teva pharmaceuticals usa, inc. - fentanyl citrate (unii: mun5lyg46h) (fentanyl - unii:uf599785jz) - fentanyl 200 ug - oral transmucosal fentanyl citrate (otfc) is indicated for the management of breakthrough pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg of oral hydrocodone per day, or an equianalgesic dose of another opioid. patients must remain on around-the-clock opioids when taking otfc. limitations of use: - not for use in opioid non-tolerant patients. - not for use in the management of acute or postoperative pain, including headache/migraine and dental pain [see contraindications (4)] . - as a part of the tirf rems, otfc may be dispensed by outpatient pharmacies only to outpatients enrolled in the program [see  warnings and precautions  (5.7)] . for inpatient administration of otfc, patient and prescriber enrollment are not required.  oral transmucosal fentanyl citrate (otfc) is contraindicated in: - opioid non-tolerant patients: life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients [see indications and usage ( 1), warnings and precautions (5.2)]. - significant respiratory depression [see warnings and precautions (5.2 )]. - acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department [see indications and usage (1)] . - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.11 )]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.15 )]. - known hypersensitivity to fentanyl or components of otfc (e.g., anaphylaxis, hypersensitivity) [see adverse reactions (6.2)]. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.8)] . available data with oral transmucosal fentanyl citrate (otfc) in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. there are risks to the mother and infant associated with use of otfc for an extended period of time during pregnancy (see clinical considerations). in animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. when administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival at doses within the range of the human recommended dosing. no evidence of malformations were noted in animal studies completed to date [see data] . the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset of neonatal withdrawal symptoms usually occurs in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.8)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. otfc is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including otfc, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data in women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers. transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. animal data fentanyl (25, 50, or 100 mcg/kg) citrate was administered subcutaneously to pregnant rats during the period of organogenesis (gestation day, gd 6 to 17). maternal toxicity and a decrease in fetal weights were observed at 100 mcg/kg but no teratogenicity was seen in the study (the no observed effect level of 50 mcg/kg is equivalent to 0.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl (50, 100, or 250 mcg/kg) was also administered subcutaneously to pregnant rabbits during the period of organogenesis (gd 6-18). maternal toxicity was noted at doses >100 mcg/kg. no teratogenicity was seen in the study (250 mcg/kg dose is equivalent to 3.5 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison). fentanyl has been shown to be embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.2 times the 1600 mcg dose of otfc on a mg/m2 basis) from gd 6 to 18 and 160 mcg/kg subcutaneously (1 times the 1600 mcg dose of otfc based on a mg/m2 basis). no evidence of teratogenicity was reported. no evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. the high dose was approximately 3 times the human dose of 1600 mcg otfc per pain episode on a mg/m2 basis and produced mean steady-state plasma levels that are 3.4 times higher than the mean cmax observed following administration of 1600 mcg dose of otfc in humans. in a postnatal development study, pregnant rats were treated from gd 6 through lactation day (ld) 20 with subcutaneous doses of fentanyl (25, 50, 100, and 400 mcg/kg). maternal toxicity was noted at doses >100 mcg/kg. a reduction in pup growth and delayed attainment of developmental indices were observed at >100 mcg/kg. no difference in the number of live pups/litter was seen at birth, however, pup survival at ld 4 was reduced to 48% at 400 mcg/kg and by ld 21 pup survival was reduced to 30% and 26% at 100 and 400 mcg/kg, respectively. during lactation, fentanyl-related clinical signs (decreased activity, skin cold to touch, and moribund appearance) were noted in the f1 pups, most prominently in the 400 mcg/kg group. pups from this group also had significantly reduced body weights throughout the lactation period. the dose of fentanyl administered to rats at which no developmental toxicity in the f1 generation was seen was 50 mcg/kg which is 0.6 times the exposure of a single human dose of 1600 mcg per pain episode, based on an auc comparison. risk summary fentanyl is present in breast milk. one published lactation study reports a relative infant dose of fentanyl of 0.024%. however, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with otfc. clinical considerations monitor infants exposed to otfc through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients below 16 years of age have not been established. in a clinical study, 15 opioid-tolerant pediatric patients with breakthrough pain, ranging in age from 5 to 15 years, were treated with otfc. the study was too small to allow conclusions on safety and efficacy in this patient population. twelve of the fifteen opioid-tolerant children and adolescents aged 5 to 15 years in this study received otfc at doses ranging from 200 mcg to 600 mcg. the mean (cv%; range) dose-normalized (to 200 mcg) cmax and auc0-8 values were 0.87 ng/ml (51%; 0.42-1.30) and 4.54 ng. h/ml (42%; 2.37-6.0), respectively, for children ages 5 to <11 years old (n = 3) and 0.68 ng/ml (72%; 0.15-1.44) and 8.38 (192%; 0.84-50.78), respectively, for children ages ≥11 to <16 y (n = 9). of the 257 patients in clinical studies of otfc in breakthrough cancer pain, 61 (24%) were 65 years of age and older, while 15 (6%) were 75 years of age and older. those patients over the age of 65 years were titrated to a mean dose that was about 200 mcg less than the mean dose titrated to by younger patients. no difference was noted in the safety profile of the group over 65 years of age as compared to younger patients in otfc clinical trials. elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger population. therefore, exercise caution when individually titrating otfc in elderly patients to provide adequate efficacy while minimizing risk. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of otfc slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.11)] . fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. insufficient information exists to make recommendations regarding the use of otfc in patients with impaired renal or hepatic function. fentanyl is metabolized primarily via human cytochrome p450 3a4 isoenzyme system and mostly eliminated in urine. if the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl. both male and female opioid-tolerant patients with cancer were studied for the treatment of breakthrough cancer pain. no clinically relevant sex differences were noted either in dosage requirement or in observed adverse reactions. oral transmucosal fentanyl citrate (otfc) contains fentanyl, a schedule ii controlled substance. otfc contains fentanyl, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of otfc increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of otfc with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of otfc abuse include those with a history of prolonged use of any opioid, including products containing fentanyl, those with a history of drug or alcohol abuse, or those who use otfc in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. otfc, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of otfc abuse of otfc poses a risk of overdose and death. the risk is increased with concurrent use of otfc with alcohol and/or other cns depressants. otfc is approved for oral transmucosal use only. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)].