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

lake erie medical dba quality care products llc - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 30 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve morphine sulfate extended-release for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release is not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release is contraindicated in patients with: - significant respiratory depression - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment - known or suspecte

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

st marys medical park pharmacy - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve morphine sulfate extended-release for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release is not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release is contraindicated in patients with: - significant respiratory depression - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment - known or suspect

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

lupin pharmaceuticals,inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve morphine sulfate extended-release tablets for use in patients for whom alternative treatment options (e.g., non- opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release tablets is not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release tablets are contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - 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), drug interactions (7)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.11)] - hypersensitivity (e.g., anaphylaxis) to morphine [see adverse reactions (6.2)] risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal withdrawal syndrome [see warnings and precautions (5.4)]. there are no available data with morphine sulfate extended-release tablets 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. 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 (5.4)] . 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.  morphine sulfate extended-release tablets is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate extended-release tablets, 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 (35to322 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 extended –release morphine, including morphine sulfate extended-release tablets. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with morphine sulfate extended-release tablets. clinical considerations monitor infants exposed to morphine sulfate extended-release tablets 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 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 (6.2), 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) ]. the safety and effectiveness in pediatric patients below the age of 18 have not been established. the pharmacokinetics of morphine sulfate extended-release tablets have not been studied in elderly patients. clinical studies of morphine sulfate extended-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 extended-release tablets slowly in geriatric patients and monitor closely 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 pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than usual dosage of morphine sulfate extended-release tablets and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine pharmacokinetics are altered in patients with renal failure. start these patients with a lower than usual dosage of morphine sulfate extended-release tablets and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate extended-release tablets contains morphine, a schedule ii controlled substance. morphine sulfate extended-release tablets 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 extended-release tablets can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)] . the high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse. 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 an over-the-counter or 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 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. 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. morphine sulfate extended-release tablets, 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 morphine sulfate extended-release tablets morphine sulfate extended-release tablets is for oral use only. abuse of morphine sulfate extended-release tablets poses a risk of overdose and death. this risk is increased with concurrent use of morphine sulfate extended-release tablets with alcohol and/or other cns depressants. taking cut, broken, chewed, crushed, or dissolved morphine sulfate extended-release tablets enhances drug release and increases the risk of overdose and death. due to the presence of talc as one of the excipients in morphine sulfate extended-release tablets, parenteral abuse can be expected to result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting   in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue morphine sulfate extended-release tablets in a patient physically dependent on opioids. rapid tapering of morphine sulfate extended-release tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing morphine sulfate extended-release tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of morphine sulfate extended-release tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.6),warnings and precautions (5.13)]. 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)] .

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

novel laboratories, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve morphine sulfate extended-release tablets for use in patients for whom alternative treatment options (e.g., non- opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release tablets is not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release tablets are contraindicated in patients with: - significant respiratory depression [see warnings and pr

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

sun pharmaceutical industries, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve morphine sulfate extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release tablets are not indicated as an as-needed (prn) analgesic. morphine sulfate is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - 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), drug interactions (7)] . - hypersensitivity (e.g., anaphylaxis) to morphine [see adverse reactions (6.2)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.11)] risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal withdrawal syndrome [see warnings and precautions (5.4)]. there are no available data with morphine sulfate 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 to 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. 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 to 4% and 15 to 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 (5.4)] . 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. morphine sulfate is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate, 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 extended-release morphine, including morphine sulfate. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with morphine sulfate. clinical considerations monitor infants exposed to morphine sulfate 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 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 (6.2), 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)] . the safety and effectiveness in pediatric patients below the age of 18 have not been established. the pharmacokinetics of morphine sulfate have not been studied in elderly patients.  clinical studies of morphine sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.  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 slowly in geriatric patients and monitor closely 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 pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than usual dosage of morphine sulfate and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine pharmacokinetics are altered in patients with renal failure. start these patients with a lower than usual dosage of morphine sulfate and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate extended-release tablets contain morphine, a schedule ii controlled substance. morphine sulfate extended-release tablets 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 can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)] . the high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse. 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 morphine sulfate extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing morphine sulfate, those with a history of drug or alcohol abuse, or those who use morphine sulfate extended-release tablets in combination with other abused drugs. prescription drug abuse is the intentional non-therapeutic use of an over-the-counter or 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 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. 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. morphine sulfate, 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 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 morphine sulfate morphine sulfate extended-release tablets are for oral use only. abuse of morphine sulfate poses a risk of overdose and death. this is increased with concurrent use of morphine sulfate with alcohol and/or other cns depressants.  taking cut, broken, chewed, crushed, or dissolved morphine sulfate extended-release tablets enhances drug release and increases the risk of overdose and death.  due to the presence of talc as one of the excipients in morphine sulfate, with parenteral abuse the inactive ingredients can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors).  tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.  withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue morphine sulfate in a patient physically dependent on opioids. rapid tapering of morphine sulfate in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing morphine sulfate, gradually taper the dosage using a patient-specific plan that considers the following: the dose of morphine sulfate the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.6), warnings and precautions (5.13)]. 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)] .

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physicians total care, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 10 mg in 5 ml - morphine sulfate oral solution (10 mg per 5 ml and 20 mg per 5 ml) are formulations of morphine, an opioid analgesic, indicated for the relief of moderate to severe acute and chronic pain where use of an opioid analgesic is appropriate. morphine sulfate oral solution 100 mg per 5 ml (20 mg/ml) is an opioid analgesic indicated for the relief of moderate to severe acute and chronic pain in opioid-tolerant patients. morphine sulfate oral solution 100 mg per 5 ml (20 mg/ml) may cause fatal respiratory depression when administered to patients not previously exposed to opioids. patients considered to be opioid tolerant are those who are taking at least 60 mg oral morphine per day, or at least 30 mg of oral oxycodone per day, or at least 12 mg hydromorphone per day, or an equianalgesic dose of another opioid, for a week or longer. morphine sulfate is contraindicated in patients with known hypersensitivity to morphine, morphine salts, or any components of the product. morphine sulfate is contraindicated in patients w

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nostrum laboratories, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 100 mg in 5 ml - morphine sulfate oral solution (10 mg per 5 ml and 20 mg per 5 ml) are formulations of morphine, an opioid agonist, indicated for the relief of moderate to severe acute and chronic pain where use of an opioid analgesic is appropriate. morphine sulfate oral solution 100 mg per 5 ml (20 mg/ml) is an opioid analgesic indicated for the relief of moderate to severe acute and chronic pain in opioid-tolerant patients. morphine sulfate oral solution 100 mg per 5 ml (20 mg/ml) may cause fatal respiratory depression when administered to patients not previously exposed to opioids. patients considered to be opioid tolerant are those who are taking at least 60 mg oral morphine per day, or at least 30 mg of oral oxycodone per day, or at least 12 mg hydromorphone per day, or an equianalgesic dose of another opioid, for a week or longer. morphine sulfate is contraindicated in patients with known hypersensitivity to morphine, morphine salts, or any components of the product. morphine sulfate is contraindicated in patients

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redpharm drug, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)], reserve morphine sulfate extended-release for use in patients for whom alternative treatment options (e.g., non- opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. morphine sulfate extended-release is not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release is contraindicated in patients with: significant respiratory depression [see warnings and precautions (5.2)] acute or severe bronchial asthma in an unmonitored setting or

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redpharm drug, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate tablets are indicated for the management of acute and chronic 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 tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: • have not been tolerated, or are not expected to be tolerated, • have not provided adequate analgesia, or are not expected to provide adequate analgesia. morphine sulfate tablets are 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 (5.5)]. • concurrent use of monoamine oxidase inhibitors (maois) or

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mckesson corporation - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets  are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use morphine sulfate extended-release tablets are contraindicated in patients with: 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. observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see warnings and precautions (5.3)]. teratogenic effects (pregnancy category c) there are no adequate and well-controlled studies in pregnant women. morphine sulfate extended-release tablets should be used during pregnancy only if the potential benefit justifies the potential r