Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - naloxone hydrochloride (unii: f850569pqr) (naloxone - unii:36b82amq7n) - naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids including propoxyphene, methadone, and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol and cyclazocine. naloxone hydrochloride is also indicated for the diagnosis of suspected or known acute opioid overdosage. naloxone may be useful as an adjunctive agent to increase blood pressure in the management of septic shock (see clinical pharmacology, adjunctive use in septic shock ). naloxone hydrochloride injection is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients contained in the formulation. naloxone hydrochloride injection is an opioid antagonist. physical dependence associated with the use of naloxone hydrochloride injection has not been reported. tolerance to the opioid antagonist effect of naloxone is not known to occur.

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - deferoxamine mesylate (unii: v9tko7eo6k) (deferoxamine - unii:j06y7mxw4d) - deferoxamine mesylate 500 mg - deferoxamine mesylate for injection, usp is indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias. acute iron intoxication deferoxamine mesylate is an adjunct to, and not a substitute for, standard measures used in treating acute iron intoxication, which may include the following: induction of emesis with syrup of ipecac; gastric lavage; suction and maintenance of a clear airway; control of shock with intravenous fluids, blood, oxygen, and vasopressors; and correction of acidosis. chronic iron overload deferoxamine mesylate can promote iron excretion in patients with secondary iron overload from multiple transfusions (as may occur in the treatment of some chronic anemias, including thalassemia). long-term therapy with deferoxamine mesylate slows accumulation of hepatic iron and retards or eliminates progression of hepatic fibrosis. iron mobilization with deferoxamine mesylate is relatively poor in patients under the age of 3 years with relativ

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - dobutamine hydrochloride (unii: 0wr771djxv) (dobutamine - unii:3s12j47372) - dobutamine 200 mg in 100 ml - dobutamine in 5% dextrose injection, usp is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures. experience with intravenous dobutamine in controlled trials does not extend beyond 48 hours of repeated boluses and/or continuous infusions. whether given orally, continuously intravenously, or intermittently intravenously, neither dobutamine nor any other cyclic-amp-dependent inotrope has been shown in controlled trials to be safe or effective in the long-term treatment of congestive heart failure. in controlled trials of chronic oral therapy with various such agents, symptoms were not consistently alleviated, and the cyclic-amp-dependent inotropes were consistently associated with increased risks of hospitalization and death. patients with nyha class iv symptoms appeared to be at particular risk. dobutamine in 5% dext

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - isoleucine (unii: 04y7590d77) (isoleucine - unii:04y7590d77), leucine (unii: gmw67qnf9c) (leucine - unii:gmw67qnf9c), lysine acetate (unii: ttl6g7liwz) (lysine - unii:k3z4f929h6), methionine (unii: ae28f7pnpl) (methionine - unii:ae28f7pnpl), phenylalanine (unii: 47e5o17y3r) (phenylalanine - unii:47e5o17y3r), threonine (unii: 2zd004190s) (threonine - unii:2zd004190s), tryptophan (unii: 8duh1n11bx) (tryptophan - unii:8duh1n11bx), valine (unii: hg18b9yrs7) (valine - unii:hg18b9yrs7), alanine (unii: of5 - aminosyn-pf 10%, sulfite-free, (an amino acid injection — pediatric formula) is indicated for the nutritional support of infants (including those of low birth weight) and young children requiring tpn via either central or peripheral infusion routes. parenteral nutrition with aminosyn-pf 10% is indicated to prevent nitrogen and weight loss or treat negative nitrogen balance in infants and young children where (1) the alimentary tract by the oral gastrostomy, or jejunostomy route, cannot or should not be used or adequate protein intake is not feasible by these routes; (2) gastrointestinal absorption of protein is impaired; or (3) protein requirements are substantially increased as with extensive burns. dosage, route of administration, and concomitant infusion of non-protein calories are dependent on various factors, such as nutritional and metabolic status of the patient, anticipated duration of parenteral nutrition support, and vein tolerance. see dosage and administration for additional information. centr

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - milrinone lactate (unii: 9k8xr81mo8) (milrinone - unii:ju9yax04c7) - milrinone is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. patients receiving milrinone should be observed closely with appropriate electrocardiographic equipment. the facility for immediate treatment of potential cardiac events, which may include life-threatening ventricular arrythmias, must be available. the majority of experience with intravenous milrinone has been in patients receiving digoxin and diuretics. there is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours. milrinone is contraindicated in patients who are hypersensitive to it. solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - meperidine hydrochloride (unii: n8e7f7q170) (meperidine - unii:9e338qe28f) - meperidine hydrochloride 25 mg in 1 ml - demerol injection is indicated for preoperative medication, support of anesthesia, and obstetrical analgesia. demerol 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, which can occur at any dosage or duration [see warnings and precautions (5.1)] , reserve demerol injection for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): demerol injection should not be used for an extended period of time unless the ‎pain remains severe enough to require an opioid analgesic and for which ‎alternative treatment options continue to be inadequate.‎ use of demerol injection for an extended period of time may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine. demerol injection is contraindicated in patients with: risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with demerol injection are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. there are adverse outcomes reported with fetal exposure to opioid analgesics (see clinical ‎‎considerations) . formal animal reproduction studies have not been conducted with meperidine. neural tube defects (exencephaly and cranioschisis) have been reported in hamsters administered a single bolus dose of meperidine during a critical period of organogenesis at 0.85 and 1.5 times the total human daily dose of 1200 mg. [see data ] the background risk of major birth defects and miscarriage for the indicated population is unknown. all ‎‎pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, 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 (5.4)] . 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. demerol 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 demerol 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 formal reproductive and developmental toxicology studies for meperidine have not been completed. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of meperidine hydrochloride (127 and 218 mg/kg, respectively) on gestation day 8 to pregnant hamsters (0.85 and 1.5 times the total daily dose of 1200 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. risk summary meperidine appears in the milk of nursing mothers receiving the drug. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for demerol injection and any potential adverse effects on the breastfed infant from demerol injection or from the underlying maternal condition. clinical considerations monitor infants exposed to demerol injection through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6), clinical pharmacology (12.2), nonclinical pharmacology (13.1)]. the safety and efficacy of demerol injection in patients less than 18 years of age have not been established. the safety and effectiveness of meperidine in pediatric patients has not been established. literature reports indicate that meperidine has a slower elimination rate in neonates and young infants compared to older children and adults. neonates and young infants may also be more susceptible to the effects, especially the respiratory depressant effects. if meperidine use is contemplated in neonates or young infants, any potential benefits of the drug need to be weighed against the relative risk of the patient. elderly patients (aged 65 years or older) may have increased sensitivity to meperidine. 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 demerol injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.2)] . meperidine 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. accumulation of meperidine and/or its active metabolite, normeperidine, can also occur in patients with hepatic impairment. elevated serum levels have been reported to cause central nervous system excitatory effects. meperidine should therefore be used with caution in patients with hepatic impairment. titrate the dosage of demerol injection slowly in patients with hepatic impairment and monitor closely for signs of central nervous system and respiratory depression. accumulation of meperidine and/or its active metabolite, normeperidine, can occur in patients with renal impairment. meperidine should therefore be used with caution in patients with renal impairment. titrate the dosage of demerol injection slowly in patients with renal impairment and monitor closely for signs of central nervous system and respiratory depression. demerol injection contains meperidine, a schedule ii controlled substance. demerol injection contains meperidine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)]. misuse is the intentional use, for therapeutic purposes, of a drug by an ‎individual in a way other than prescribed by a healthcare provider or for ‎whom it was not prescribed.‎ abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling ‎drug use (e.g., continuing drug use despite harmful consequences, giving ‎a higher priority to drug use than other activities and obligations), and ‎possible tolerance or physical dependence.‎ misuse and abuse of demerol injection increases risk of overdose, ‎which may lead to central nervous system and respiratory depression, ‎hypotension, seizures, and death. the risk is increased with concurrent ‎abuse of demerol injection with alcohol and/or other cns depressants. abuse of and addiction to opioids in some ‎individuals may not be accompanied by concurrent tolerance and ‎symptoms of physical dependence. in addition, abuse of opioids can occur ‎in the absence of addiction.‎ all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. ‎patients at high risk of demerol injection abuse include those with a ‎history of prolonged use of any opioid, including products containing meperidine, those with a history of drug or alcohol abuse, or those who use demerol injection in ‎combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. demerol injection, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of demerol injection abuse of demerol injection poses a risk of overdose and death. the risk is increased with concurrent abuse of demerol injection with alcohol and/or other cns 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 use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. demerol injection should not be abruptly discontinued in a physically-dependent patient [see dosage and administration (2.4)] . if demerol injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically characterized by restlessness, lacrimation, rhinorrhea, 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)] . parenteral drug products should be inspected visually for particulate matter and discoloration prior to ‎administration, whenever solution and container permit. do not use if color is darker than pale yellow, if it ‎is discolored in any other way, or if it contains a precipitate. instructions for use - carpuject™ single-dose cartridge carpuject™ single-dose cartridges with luer lock are packaged in a slim-pak™ tamper detection package. note that a needle is not included. before use, read all instructions for using the carpuject™ syringe, which are contained in the product insert for‎ the reusable carpuject™ holder before use. carpuject™ single-dose cartridges are to be used only with carpuject™ holders. note: to prevent needlestick injuries, do not recap, purposely bend, or break by hand used ‎needles. do not recap, purposely bend, or break by hand blunt cannulas. instructions for use - nexject™ single-dose prefilled syringe note : to prevent needlestick injuries, do not recap, purposely bend, or break by hand used ‎needles. do not recap, purposely bend, or break by ‎hand blunt cannulas. distributed by hospira, inc., lake forest, il 60045 usa lab-1387-2.0 revised: 12/2023

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget's disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5)] . zoledronic acid is contraindicated in patients with the following conditions: risk summary available data on the use of zoledronic acid in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. discontinue zoledronic acid when pregnancy is recognized. in animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent t

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - hetastarch (unii: 875y4127ea) (hetastarch - unii:875y4127ea) - hetastarch 6 g in 100 ml - hextend (6% hetastarch in lactated electrolyte injection) is indicated in the treatment of hypovolemia when plasma volume expansion is desired in settings where adequate alternative treatment is unavailable. it is not a substitute for blood or plasma. do not use hes products, including hextend, unless adequate alternative treatment is unavailable.

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - cimetidine (unii: 80061l1wgd) (cimetidine - unii:80061l1wgd) - injection, solution - 6 mg in 1 ml - cimetidine hydrochloride injection is indicated in: (1) short-term treatment of active duodenal ulcer. most patients heal within 4 weeks and there is rarely reason to use cimetidine at full dosage for longer than 6 to 8 weeks (see dosage and administration − duodenal ulcer). concomitant antacids should be given as needed for relief of pain. however, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of oral cimetidine. (2) maintenance therapy for duodenal ulcer patients at reduced dosage after healing of active ulcer. patients have been maintained on continued treatment with cimetidine 400 mg h.s. for periods of up to five years. (3) short-term treatment of active benign gastric ulcer. there is no information concerning usefulness of treatment periods of longer than 8 weeks. (4) prevention of upper gastrointestinal bleeding in critically ill patients. (5) the treatment of pathological hypersecretory conditions

Egyesült Államok - angol - NLM (National Library of Medicine)

hospira, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - preservative-free morphine sulfate injection is indicated for: limitations of use preservative-free morphine sulfate injection is not for use in continuous microinfusion devices. because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions (5.2)] , reserve preservative-free morphine sulfate injection for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): preservative-free morphine sulfate injection should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. preservative-free morphine sulfate injection is contraindicated in patients with: neuraxial administration of preservative-free morphine sulfate injection is contraindicated in patients with: risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)] . available data with preservative-free morphine sulfate injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. there are adverse outcomes reported with fetal exposure to opioid analgesics (see clinical considerations) . published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see error! hyperlink reference not valid. ] . 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 error! hyperlink reference not valid. ]. based on animal data, advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, 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 (5.5)]. labor or delivery opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate. preservative-free morphine sulfate injection is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including preservative-free morphine sulfate injection, can prolong labor through actions that 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 dilatation, 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 nonrandomized 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 preservative-free 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 preservative-free morphine sulfate injection and any potential adverse effects on the breastfed infant from preservative-free morphine sulfate injection or from the underlying maternal condition. clinical considerations monitor infants exposed to preservative-free morphine sulfate injection through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6), clinical pharmacology (12.2)] . 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)] . adequate studies to establish the safety and effectiveness of spinal morphine in pediatric patients have not been performed, and usage in this population is not recommended. elderly patients (aged 65 years or older) may have increased sensitivity to preservative-free morphine sulfate injection. 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 preservative-free morphine sulfate injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.9)] . the pharmacodynamic effects of neuraxial morphine in the elderly are more variable than in the younger population. 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. initial doses should be based on careful clinical observation following “test doses”, after making due allowances for the effects of the patient’s age and infirmity on his/her ability to clear the drug, particularly in patients receiving epidural morphine. 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. the elimination half-life of morphine may be prolonged in patients with reduced metabolic rates and with hepatic and/or renal dysfunction. hence, care should be exercised in administering preservative-free morphine sulfate injection epidurally to patients with these conditions. high blood morphine levels, due to reduced clearance, may take several days to develop. preservative-free morphine sulfate injection contains morphine, a schedule ii controlled drug substance. preservative-free morphine sulfate injection contains morphine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.2)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, nontherapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of preservative-free morphine sulfate injection increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of preservative-free morphine sulfate injection with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of preservative-free morphine sulfate injection abuse include those with a history of prolonged use of any opioid, including products containing morphine, those with a history of drug or alcohol abuse, or those who use preservative-free morphine sulfate injection in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. preservative-free morphine sulfate injection, like other opioids, can be diverted for nonmedical 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of preservative-free morphine sulfate injection abuse of preservative-free morphine sulfate injection poses a risk of overdose and death. the risk is increased with concurrent use of preservative-free morphine sulfate injection with alcohol and/or other cns 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 use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. preservative-free morphine sulfate injection should not be abruptly discontinued in a physically-dependent patient [see dosage and administration (2.6)] . if preservative-free morphine sulfate injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically characterized by restlessness, lacrimation, rhinorrhea, 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)] .