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

mikart, llc - hydrocodone bitartrate (unii: no70w886kk) (hydrocodone - unii:6yks4y3wq7), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - hydrocodone bitartrate and acetaminophen oral solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve hydrocodone bitartrate and acetaminophen oral solution for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): - have not been tolerated, or are not expected to be tolerated - have not provided adequate analgesia, or are not expected to provide adequate analgesia hydrocodone bitartrate and acetaminophen oral solution is contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see

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

fresenius kabi usa, llc - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥ 0.1 mg/kg/day (6% of the human recommended dose based on mg/m2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥ 0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant injection, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the last dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant injection can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant injection may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change=-0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change=-1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (cmin,ss ) and aucss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant in study 0021 and study 0020, respectively. fulvestrant is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter- acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant injection 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2) and warnings and precautions (5.2)]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

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

fh2 pharma llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - oxycodone and acetaminophen tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve oxycodone and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia oxycodone and acetaminophen tablets are contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see wa

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

specgx llc - levorphanol tartrate (unii: 04wqu6t9qi) (levorphanol - unii:27618j1n2x) - levorphanol tartrate tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses (see warnings ), reserve levorphanol tartrate tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia. levorphanol tartrate tablets are contraindicated in patients with: - significant respiratory depression (see warnings ) - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see warnings ) - known or suspected gastrointestinal obstruction, including paralytic ileus (see warnings ) - hypersensitivity to levorphanol or any of the formulation excipients (e.g., anaphylaxis) (s

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

northstar rx llc - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant injection [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant injection, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant injection can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant injection may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change=-0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change=-1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant injection on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant injection. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant injection. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (cmin,ss ) and aucss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant injection 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant injection in study 0021 and study 0020, respectively. fulvestrant injection is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant injection has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant injection 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2) and warnings and precautions (5.2)]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

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

forte bio-pharma llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - oxycodone and acetaminophen tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve oxycodone and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia oxycodone and acetaminophen tablets are contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings ] - hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis) [see warnings , adverse reactions ] oxycodone and acetaminophen tablets contain oxycodone, a schedule ii controlled substance. oxycodone and acetaminophen tablets contain oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. oxycodone and acetaminophen tablets can be abused and is subject to misuse, addiction, and criminal diversion [see warnings ]. all patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “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 health care provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. oxycodone and acetaminophen tablets, like other opioids, can be diverted for non-medical 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 re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of oxycodone and acetaminophen tablets oxycodone and acetaminophen tablets are for oral use only. abuse of oxycodone and acetaminophen tablets poses a risk of overdose and death. the risk is increased with concurrent abuse of oxycodone and acetaminophen tablets with alcohol and other central nervous system depressants. acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), 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 opioid usage. do not abruptly discontinue oxycodone and acetaminophen tablets in a patient physically dependent on opioids. rapid tapering of oxycodone and acetaminophen tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing oxycodone and acetaminophen tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone and acetaminophen tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration , warnings ]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see precautions; pregnancy ].

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

athenex pharmaceutical division, llc. - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant injection [see adverse reactions ( 6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology ( 12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m 2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m 2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m 2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m 2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m 2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m 2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m 2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m 2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant can cause fetal harm when administered to a pregnant woman [see use in specific populations ( 8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology ( 13.1)] . safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change = -0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change = -1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant injection. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant injection. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (c min,ss ) and auc ss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant injection in study 0021 and study 0020, respectively. fulvestrant is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant injection has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration ( 2.2) and warnings and precautions ( 5.2)] . negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

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

veroscience llc - bromocriptine mesylate (unii: ffp983j3od) (bromocriptine - unii:3a64e3g5zo) - cycloset is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. - cycloset should not be used to treat type 1 diabetes or diabetic ketoacidosis. - limited efficacy data in combination with thiazolidinediones. - efficacy has not been confirmed in combination with insulin. cycloset is contraindicated in: - patients with known hypersensitivity to bromocriptine, ergot-related drugs, or any of the excipients in cycloset. - patients with syncopal migraine. bromocriptine increases the likelihood of a hypotensive episode among patients with syncopal migraine. loss of consciousness during a migraine may reflect dopamine receptor hypersensitivity. cycloset is a dopamine receptor agonist and may, therefore, potentiate the risk for syncope in these patients. - women who are nursing their children. cycloset may inhibit lactation. there are postmarketing reports of stroke in this patient population although causality has not been proven [see use in specific popu

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

fh2 pharma llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - oxycodone hydrochloride and acetaminophen oral solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve oxycodone hydrochloride and acetaminophen oral solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings ] hypersensitivity

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

forte bio-pharma llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - oxycodone hydrochloride and acetaminophen oral solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see warnings ], reserve oxycodone hydrochloride and acetaminophen oral solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with: - significant respiratory depression [see warnings ] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings ] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings ] - hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis) [see warnings, adverse reactions ] oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a schedule ii controlled substance. oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. oxycodone hydrochloride and acetaminophen oral solution can be abused and is subject to misuse, addiction, and criminal diversion [see warnings ]. all patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “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 health care provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. oxycodone hydrochloride and acetaminophen oral solution, like other opioids, can be diverted for non-medical 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 re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of oxycodone hydrochloride and acetaminophen oral solution oxycodone hydrochloride and acetaminophen oral solution is for oral use only. abuse of oxycodone hydrochloride and acetaminophen oral solution poses a risk of overdose and death. the risk is increased with concurrent abuse of oxycodone hydrochloride and acetaminophen oral solution with alcohol and other central nervous system depressants. acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), 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 opioid usage. do not abruptly discontinue oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids. rapid tapering of oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing oxycodone hydrochloride and acetaminophen oral solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone hydrochloride and acetaminophen oral solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration , warnings ]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see precautions; pregnancy ].