アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - dexamethasone sodium phosphate (unii: ai9376y64p) (dexamethasone - unii:7s5i7g3jql) - dexamethasone 4 mg in 1 ml - - intravenous or intramuscular administration. when oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, those products labeled for intravenous or intramuscular use are indicated as follows: endocrine disorders. primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance). acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used). preoperatively, and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful. shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - leucovorin calcium (unii: rpr1r4c0p4) (leucovorin - unii:q573i9dvlp) - leucovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma. leucovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.  leucovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible.  leucovorin is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. leucovorin should not be mixed in the same infusion as 5-fluorouracil because a precipitate may form. leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin b12 . a hematologic remission may occur while neurologic manifestations continue to progress.

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - methocarbamol (unii: 125od7737x) (methocarbamol - unii:125od7737x) - the injection form of methocarbamol is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.  the mode of action of this drug has not been clearly identified, but may be related to its sedative properties.  methocarbamol does not directly relax tense skeletal muscles in man. methocarbamol injection should not be administered to patients with known or suspected renal pathology.  this caution is necessary because of the presence of polyethylene glycol 300 in the vehicle. a much larger amount of polyethylene glycol 300 than is present in recommended doses of methocarbamol injection is known to have increased pre-existing acidosis and urea retention in patients with renal impairment.  although the amount present in this preparation is well within the limits of safety, caution dictates this contraindication. methocarbamol injection is contraindicated in patients hypersensitive to methocarbamol or to any of the i

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - leucovorin calcium (unii: rpr1r4c0p4) (leucovorin - unii:q573i9dvlp) - leucovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma. leucovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. leucovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible. leucovorin is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. leucovorin should not be mixed in the same infusion as 5-fluorouracil because a precipitate may form. leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin b12 . a hematologic remission may occur while neurologic manifestations continue to progress.

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - neostigmine methylsulfate (unii: 98imh7m386) (neostigmine - unii:3982twq96g) - neostigmine methylsulfate injection, a cholinesterase inhibitor, is indicated for reversal of the effects of nondepolarizing neuromuscular blocking agents (nmba) after surgery. neostigmine is contraindicated in patients with: - known hypersensitivity to neostigmine methylsulfate (known hypersensitivity reactions have included urticaria, angioedema, erythema multiforme, generalized rash, facial swelling, peripheral edema, pyrexia, flushing, hypotension, bronchospasm, bradycardia and anaphylaxis). - peritonitis or mechanical obstruction of the urinary or intestinal tracts. risk summary there are no adequate or well-controlled studies of neostigmine methylsulfate injection in pregnant women. it is not known whether neostigmine methylsulfate injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. the incidence of malformations in human pregnancies has not been established for neostigmine as the data are limited. all pregnancies, regardless of drug exposure, have a background risk of 2 to 4% for major birth defects, and 15 to 20% for pregnancy loss. no adverse effects were noted in rats or rabbits treated with human equivalent doses of neostigmine methylsulfate doses up to 8.1 and 13 mcg/kg/day, respectively, during organogenesis (0.1 to 0.2-times the maximum recommended human dose of 5 mg/60 kg person/day based on body surface area comparisons). anticholinesterase drugs, including neostigmine may cause uterine irritability and induce premature labor when administered to pregnant women near term. neostigmine methylsulfate injection should be given to a pregnant woman only if clearly needed. data animal data it is not known whether neostigmine methylsulfate injection is excreted in human milk. because many drugs are excreted in human milk and because of the potential for serious adverse reactions from neostigmine methylsulfate injection in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. data from published literature support the intravenous use of neostigmine methylsulfate for reversal of nondepolarizing neuromuscular blocking agents in all pediatric age groups. recovery of neuromuscular activity occurs more rapidly with smaller doses of cholinesterase inhibitors in infants and children than in adults. however, infants and small children may be at greater risk of complications from incomplete reversal of neuromuscular blockade due to decreased respiratory reserve. the risks associated with incomplete reversal outweigh any risk from giving higher doses of neostigmine methylsulfate (up to 0.07 mg/kg or up to a total of 5 mg, whichever is lower). the dose of neostigmine methylsulfate required to reverse neuromuscular blockade in children varies between 0.03 mg to 0.07 mg/kg, the same dose range shown to be effective in adults, and should be selected using the same criteria as used for adult patients [see clinical pharmacology (12.3) ]. since the blood pressure in pediatric patients, particularly infants and neonates is sensitive to changes in heart rate, the effects of an anticholinergic agent (e.g., atropine) should be observed prior to administration of neostigmine to lessen the probability of bradycardia and hypotension. elderly patients are likely to have decreased renal function, which may prolong the duration of action of neostigmine methylsulfate. however, elderly patients also experience slower spontaneous recovery from neuromuscular blocking agents. therefore, dosage adjustments are generally not needed in geriatric patients; however, they should be monitored for longer periods than younger adults to assure additional doses of neostigmine methylsulfate injection are not required. the duration of monitoring should be predicated on the anticipated duration of action for the neuromuscular blocking agents used on the patient. elimination half-life of neostigmine was prolonged in anephric patients compared to normal subjects, so neostigmine concentration may increase in patients with impaired renal functions. although no adjustments to neostigmine methylsulfate injection dosing appear to be warranted in patients with impaired renal function, they should be closely monitored for a longer period of time. to assure the effects of the neuromuscular blocking agent, particularly one cleared by the kidneys, do not persist beyond those of neostigmine methylsulfate injection, the interval for re-dosing the neuromuscular blocking agent during the surgical procedure may be useful in determining whether, and to what extent, post-operative monitoring needs to be extended. the pharmacokinetics of neostigmine methylsulfate in patients with hepatic impairment have not been studied. neostigmine is metabolized by microsomal enzymes in the liver so neostigmine concentration may increase in patients with impaired hepatic functions. although no adjustments to the dosing of neostigmine methylsulfate injection appear to be warranted in patients with hepatic insufficiency, patients should be carefully monitored for a longer period of time. if hepatically cleared neuromuscular blocking agents were used during the surgical procedure, their duration of action may also be prolonged by hepatic insufficiency. this could result in the effects of the neuromuscular blocking agent outlasting those of neostigmine methylsulfate injection. in this regard, the interval for re-dosing the neuromuscular blocking agent during the surgical procedure may be useful in determining whether, and to what extent, post-operative monitoring needs to be extended. instructions for use figure 1: outer packaging and prefilled syringe notes: - inspect the outer packaging (blister pack) to confirm the integrity of the packaging. do not use if the blister pack or the prefilled syringe has been damaged. - remove the syringe from the outer packaging. (see figure 2) figure 2 remove the syringe from the outer packaging. (see figure 2) figure 2 - visually inspect the syringe. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. visually inspect the syringe. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. - twist off the syringe tip cap. do not remove the label around the luer lock collar. (see figure 3) figure 3 twist off the syringe tip cap. do not remove the label around the luer lock collar. (see figure 3) figure 3 - expel air bubble(s). adjust the dose (if applicable). - administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. - discard the used syringe into an appropriate receptacle. for more information concerning this drug, please call fresenius kabi usa, llc at 1-800-551-7176. to report suspected adverse reactions, contact fresenius kabi usa, llc at 1-800-551-7176 or fda at 1-800-fda-1088 or www.fda.gov/medwatch. u.s. patents 9,731,082 and 10,661,018 lake zurich, il 60047 www.fresenius-kabi.com/us 451585b

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - dilaudid injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. limitations of use: because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve dilaudid injection 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 dilaudid injection is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.2)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.9)] - hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite containing medications (e.g., anaphylaxis) [see warnings and precautions (5.13)] risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.3)] . there are no available data with dilaudid injection in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, reduced postnatal survival of pups, and decreased body weight were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (hdd), respectively. in published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the hdd and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the hdd to pregnant mice. no malformations were noted at 4 or 40.5 times the hdd in pregnant rats or rabbits, respectively [see data ]. based on animal 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. 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 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.3)]. 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. dilaudid injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including dilaudid injection, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). there was no evidence of malformations or embryotoxicity reported. pregnant rabbits were treated with hydromorphone hydrochloride from gestation day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). there was no evidence of malformations or embryotoxicity reported. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on gestation day 8 to pregnant hamsters (6.4 to 87.2 times the hdd of 24 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. no neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day). in a published study, cf-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (gestation days 7 to 10). soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. the findings cannot be clearly attributed to maternal toxicity. increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from gestation day 7 to lactation day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested. risk summary low levels of opioid analgesics have been detected in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for dilaudid injection and any potential adverse effects on the breastfed infant from dilaudid injection or from the underlying maternal condition. clinical considerations monitor infants exposed to dilaudid injection through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. infertility chronic use of opioids 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), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of dilaudid injection in pediatric patients has not been established. elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of dilaudid injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.5)]. hydromorphone 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. the pharmacokinetics of hydromorphone are affected by hepatic impairment. due to increased exposure of hydromorphone, patients with moderate hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and closely monitored during dose titration. the pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. a further increase in cmax and auc of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see clinical pharmacology (12.3]. the pharmacokinetics of hydromorphone are affected by renal impairment. start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. patients with renal impairment should be closely monitored during dose titration [see clinical pharmacology (12.3)]. dilaudid injection contains hydromorphone, which is a schedule ii controlled substance. dilaudid injection contains hydromorphone hydrochloride, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. dilaudid injection can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)]. all patients treated with opioids require careful monitoring for signs of abuse and addiction, because 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 of prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare providers. “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. healthcare 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. dilaudid injection, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful recordkeeping 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 dilaudid injection abuse of dilaudid injection poses a risk of overdose and death. the risk is increased with concurrent use of dilaudid injection with alcohol and other central nervous system depressants. 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 results in withdrawal symptoms after abrupt discontinuation of 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. dilaudid injection should not be abruptly discontinued in a physically-dependent patient [see dosage and administration (2.6)] . if dilaudid injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 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)]. instructions for use figure 1: outer packaging (microvault ® ) and prefilled syringe notes: - once removed from the bundle, inspect the outer packaging by verifying: - integrity of the tube and the cap. - tamper evident seal is intact (outer shrink wrap is not broken). do not use if the outer packaging has been damaged. - hold the outer packaging with both hands. to break the tamper evident seal, hold the tube and the cap close to the seal, and twist until broken. (see figure 2) figure 2 hold the outer packaging with both hands. to break the tamper evident seal, hold the tube and the cap close to the seal, and twist until broken. (see figure 2) figure 2 - remove the cap of the outer packaging by pulling it straight away from the tube to avoid dislodging the plunger rod of the syringe. (see figure 3) figure 3 remove the cap of the outer packaging by pulling it straight away from the tube to avoid dislodging the plunger rod of the syringe. (see figure 3) figure 3 - remove the syringe from the tube. - visually inspect the syringe. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. - twist off the syringe tip cap. do not remove the plastic wrap label around the luer lock collar. (see figure 4) figure 4 twist off the syringe tip cap. do not remove the plastic wrap label around the luer lock collar. (see figure 4) figure 4 - expel air bubble(s). adjust the dose (if applicable). - administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. - discard the used syringe into an appropriate receptacle. for more information concerning this drug, please call fresenius kabi usa, llc at 1-800-551-7176. to report suspected adverse reactions, contact fresenius kabi usa, llc at 1-800-551-7176 or fda at 1-800fda-1088 or www.fda.gov/medwatch. lake zurich, il 60047 www.fresenius-kabi.com/us rev. 01/2020 451594b dilaudid is a licensed trademark of purdue pharma l.p. u.s. patents 9,731,082 and 10,064,998

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi, usa llc - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate injection 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 and precautions (5.1)] , reserve morphine sulfate injection 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 morphine sulfate injection is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions (5.7)]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.11)] - hypersensitivity to morphine (e.g., anaphylaxis) [see adverse reactions (6)] risk summary prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.3)]. there are no available data with morphine sulfate injection in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see human data]. in published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (hdd) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the hdd in the rabbit, growth retardation at 6 times the hdd in the rat, and axial skeletal fusion and cryptorchidism at 16 times the hdd in the mouse. administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3-4 times the hdd; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the hdd [see animal data] . based on animal data, advise pregnant women of the potential risk to a fetus. 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 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.3)] . 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. morphine sulfate injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate injection, 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 the results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and non-randomized study design. animal data formal reproductive and developmental toxicology studies for morphine have not been conducted. exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (hdd). neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35-322 mg/kg) on gestation day 8 to pregnant hamsters (4.7 to 43.5 times the hdd). a no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (sc) injection of morphine sulfate to pregnant mice (100-500 mg/kg) on gestation day 8 or 9 at 200 mg/kg or greater (16 times the hdd) and fetal resorption at 400 mg/kg or higher (32 times the hdd). no adverse effects were noted following 100 mg/kg morphine in this model (8 times the hdd). in one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the hdd), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. the effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. the clinical significance of this report is not clear. decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the hdd) from gestation day 7 to 9. there was no evidence of malformations despite maternal toxicity (10% mortality). in a second rat study, decreased fetal weight and increased incidences of growth retardation were noted at 35 mg/kg/day (5.7 times the hdd) and there was a reduced number of fetuses at 70 mg/kg/day (11.4 times the hdd) when pregnant rats were treated with 10, 35, or 70 mg/kg/day morphine sulfate via continuous infusion from gestation day 5 to 20. there was no evidence of fetal malformations or maternal toxicity. an increased incidence of abortion was noted in a study in which pregnant rabbits were treated with 2.5 (0.8 times the hdd) to 10 mg/kg morphine sulfate via subcutaneous injection from gestation day 6 to 10. in a second study, decreased fetal body weights were reported following treatment of pregnant rabbits with increasing doses of morphine (10-50 mg/kg/day) during the pre-mating period and 50 mg/kg/day (16 times the hdd) throughout the gestation period. no overt malformations were reported in either publication; although only limited endpoints were evaluated. in published studies in rats, exposure to morphine during gestation and/or lactation periods is associated with: decreased pup viability at 12.5 mg/kg/day or greater (2 times the hdd); decreased pup body weights at 15 mg/kg/day or greater (2.4 times the hdd); decreased litter size, decreased absolute brain and cerebellar weights, cyanosis, and hypothermia at 20 mg/kg/day (3.2 times the hdd); alteration of behavioral responses (play, social-interaction) at 1 mg/kg/day or greater (0.2 times the hdd); alteration of maternal behaviors (e.g., decreased nursing and pup retrievals) in mice at 1 mg/kg or higher (0.08 times the hdd) and rats at 1.5 mg/kg/day or higher (0.2 times the hdd); and a host of behavioral abnormalities in the offspring of rats, including altered responsiveness to opioids at 4 mg/kg/day (0.7 times the hdd) or greater. fetal and/or postnatal exposure to morphine in mice and rats has been shown to result in morphological changes in fetal and neonatal brain and neuronal cell loss, alteration of a number of neurotransmitter and neuromodulator systems, including opioid and non-opioid systems, and impairment in various learning and memory tests that appear to persist into adulthood. these studies were conducted with morphine treatment usually in the range of 4 to 20 mg/kg/day (0.7 to 3.2 times the hdd). additionally, delayed sexual maturation and decreased sexual behaviors in female offspring at 20 mg/kg/day (3.2 times the hdd), and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed at 20 mg/kg/day (3.2 times the hdd). decreased litter size and viability were observed in the offspring of male rats that were intraperitoneally administered morphine sulfate for 1 day prior to mating at 25 mg/kg/day (4.1 times the hdd) and mated to untreated females. decreased viability and body weight and/or movement deficits in both first and second generation offspring were reported when male mice were treated for 5 days with escalating doses of 120 to 240 mg/kg/day morphine sulfate (9.7 to 19.5 times the hdd) or when female mice treated with escalating doses of 60 to 240 mg/kg/day (4.9 to 19.5 times the hdd) followed by a 5-day treatment-free recovery period prior to mating. similar multigenerational findings were also seen in female rats pre-gestationally treated with escalating doses of 10 to 22 mg/kg/day morphine (1.6 to 3.6 times the hdd). risk summary morphine is present in breast milk. published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine auc ratio of 2.5:1 measured in one lactation study. however, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. lactation studies have not been conducted with morphine sulfate injection and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for morphine sulfate injection and any potential adverse effects on the breastfed infant from morphine sulfate injection or from the underlying maternal condition. clinical considerations infants exposed to morphine sulfate injection through breast milk should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. infertility chronic use of opioids 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)]. in published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see nonclinical toxicology (13)] . the safety and effectiveness of morphine sulfate injection in pediatric patients below the age of 18 have not been established. the pharmacodynamic effects of morphine in the elderly are more variable than in the younger population. older patients will vary widely in the effective initial dose, rate of development of tolerance and the frequency and magnitude of associated adverse effects as the dose is increased. elderly patients (aged 65 years or older) may have increased sensitivity to morphine. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of morphine sulfate injection slowly in geriatric patients and monitor for signs of central nervous system and respiratory depression [see warnings and precautions (5.6)] . morphine 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. morphine sulfate pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than normal dosage of morphine sulfate injection and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate pharmacokinetics are altered in patients with renal failure. start these patients with a lower than normal dosage of morphine sulfate injection and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate injection contains morphine, a schedule ii controlled substance. morphine sulfate injection contains morphine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and tapentadol. morphine sulfate injection can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)]. all patients treated with opioids require careful monitoring for signs of abuse and addiction, because 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 healthcare 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. morphine sulfate injection, 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. 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 results 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. morphine sulfate injection should not be abruptly discontinued in a physically-dependent patient [see dosage and administration (2.4)]. if morphine sulfate injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 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)] . instructions for use figure 1: outer packaging (microvault) and prefilled syringe notes: - once removed from the bundle, inspect the outer packaging by verifying: - integrity of the tube and the cap. - tamper evident seal is intact (outer shrink wrap is not broken). do not use if the outer packaging has been damaged. - hold the outer packaging with both hands. to break the tamper evident seal, hold the tube and the cap close to the seal, and twist until broken. (see figure 2) figure 2 figure 2 - remove the cap of the outer packaging by pulling it straight away from the tube to avoid dislodging the plunger rod of the syringe. (see figure 3) figure 3 figure 3 - remove the syringe from the tube. - visually inspect the syringe. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. - twist off the syringe tip cap. do not remove the plastic wrap label around the luer lock collar. (see figure 4) figure 4 figure 4 - expel air bubble(s). adjust the dose (if applicable). - administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. - discard the used syringe into an appropriate receptacle. for more information concerning this drug, please call fresenius kabi usa, llc at 1-800-551-7176. to report suspected adverse reactions, contact fresenius kabi usa, llc at 1-800-551-7176 or fda at 1-800-fda-1088 or www.fda.gov/medwatch. the brand names mentioned in this document are the trademarks of their respective owners. u.s. patents 9,072,781; 9,192,608; 9,731,082; and 10,064,998 lake zurich, il 60047 www.fresenius-kabi.com/us 451652 issued: 11/2019

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - dexamethasone sodium phosphate (unii: ai9376y64p) (dexamethasone - unii:7s5i7g3jql) - - intravenous or intramuscular administration. when oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, those products labeled for intravenous or intramuscular use are indicated as follows: endocrine disorders. primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance). acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used). preoperatively, and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful. shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - bumetanide (unii: 0y2s3xuq5h) (bumetanide - unii:0y2s3xuq5h) - bumetanide injection is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. almost equal diuretic response occurs after oral and parenteral administration of bumetanide. therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route. successful treatment with bumetanide following instances  of allergic reactions  to  furosemide  suggests a lack of cross-sensitivity. bumetanide is contraindicated in anuria. although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive  renal  disease, is  an indication for  discontinuation of treatment with bumetanide. bumetanide is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the con

アメリカ合衆国 - 英語 - NLM (National Library of Medicine)

fresenius kabi usa, llc - caffeine citrate (unii: u26eo4675q) (caffeine - unii:3g6a5w338e) - caffeine citrate 20 mg in 1 ml - caffeine citrate oral solution is indicated for the short term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age. caffeine citrate is contraindicated in patients who have demonstrated hypersensitivity to any of its components.