Singapore - English - HSA (Health Sciences Authority)

ids medical systems (singapore) pte ltd - general hospital - the belimed mst-v steam sterilizer was developed for sterilizing porous and nonporous, heat-resistant and steam-resistant solids in the healthcare sector.

Singapore - English - HSA (Health Sciences Authority)

ids medical systems (singapore) pte ltd - general hospital - intended for sterilizing porous and non-porous, heat-and steam-resistant solid goods in the medical area.

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

australis crop protection pty ltd - non-ionic surfactant; paraffinic oil - emulsifiable concentrate - non-ionic surfactant emulsifiers & surfactants-noni active 210.0 g/l; paraffinic oil petroleum derivative-oil active 598.0 g/l - adjuvant - aerial spraying | broadacre cropping including fallow | cereal crop | cotton | horticultural crop | legume | spot spraying | sug - additive - refer to label | defoliation of cotton plants | defoliation aid

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

crop smart pty ltd - nonyl phenol ethoxylate; alcohol ethoxylate; paraffinic oil - oil miscible liquid - nonyl phenol ethoxylate emulsifiers & surfactants-noni active 120.0 g/l; alcohol ethoxylate emulsifiers & surfactants active 120.0 g/l; paraffinic oil petroleum derivative-oil active 582.0 g/l - wetting agent - broadacre cropping including fallow | cotton defoliation | herbicide additive | high volume spraying | horticultural crop | inse - spreading agent | wetting agent (use as directed) | improve penetrating properties

Israel - English - Ministry of Health

baxter healthcare distribution ltd., israel - calcium chloride dihydrate; icodextrin; magnesium chloride hexahydrate; sodium (s) - lactate; sodium chloride - solution for peritoneal dialysis - icodextrin 75 g/l; magnesium chloride hexahydrate 0.051 g/l; calcium chloride dihydrate 0.257 g/l; sodium (s) - lactate 4.5 g/l; sodium chloride 5.4 g/l - dextran - dextran - once daily replacement of a single glucose exchange as part of continuous ambulatory peritoneal dialysis (capd) or automated peritoneal dialysis (apd) in the treatment of chronic renal failure.

European Union - English - EMA (European Medicines Agency)

chiesi farmaceutici s.p.a - mercaptamine bitartrate - cystinosis - other alimentary tract and metabolism products, - procysbi is indicated for the treatment of proven nephropathic cystinosis. cysteamine reduces cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis patients and, when treatment is started early, it delays the development of renal failure.

Australia - English - Department of Health (Therapeutic Goods Administration)

majac medical products pty ltd - 35450 - filter, steam, delivery line - container filter round / square with indicator for sterilisation

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

golden state medical supply, inc. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j) - tramadol hydrochloride 50 mg - tramadol hydrochloride tablets are indicated in adults 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 tramadol hydrochloride 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. tramadol hydrochloride tablets 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. tramadol hydrochloride tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions ( 5.6)] . - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions ( 5.6)] . tramadol hydrochloride tablets are also 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 ( 5.12)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.16)] . - hypersensitivity to tramadol, any other component of this product or opioids [see warnings and precautions ( 5.17)] . - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions ( 7)] . 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 tramadol hydrochloride tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, tramadol administration during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd). tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the mrhd [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome can present 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 and signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions ( 5.4)] . neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported during postmarketing. 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. tramadol hydrochloride tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including tramadol hydrochloride 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. tramadol has been shown to cross the placenta. the mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. the effect of tramadol hydrochloride tablets, if any, on the later growth, development, and functional maturation of the child is unknown. data animal data tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. these doses on a mg/m 2 basis are 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd) for mouse, rat and rabbit, respectively. no drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. embryo and fetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. the dosages listed for mouse, rat and rabbit are 1.7, 1.9 and 14.6 times the mrhd, respectively. tramadol was evaluated in pre- and post-natal studies in rats. progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (1.2 times the mrhd) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (1.9 times the mrhd). risk summary tramadol hydrochloride tablets are not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. tramadol and its metabolite, o -desmethyltramadol (m1), are present in human milk. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the m1 metabolite is more potent than tramadol in mu opioid receptor binding [see clinical pharmacology ( 12)] . published studies have reported tramadol and m1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of m1, potentially leading to higher levels of m1 in breast milk that can be dangerous in their breastfed infants. in women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. 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 tramadol hydrochloride tablets  [see warnings and precautions ( 5.6)] . clinical considerations if infants are exposed to tramadol hydrochloride through breast milk, they should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. data following a single iv 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of m1. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions ( 6.2)] . the safety and effectiveness of tramadol hydrochloride tablets in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions ( 5.6)] . in some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. because of the risk of life-threatening respiratory depression and death: - tramadol hydrochloride tablets are contraindicated for all children younger than 12 years of age [see contraindications ( 4)] . - tramadol hydrochloride tablets are contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see contraindications ( 4)] . avoid the use of tramadol hydrochloride tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. a total of 455 elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride tablets in controlled clinical trials. of those, 145 subjects were 75 years of age and older. in studies including geriatric patients, treatment-limiting adverse events were higher in subjects over 75 years of age compared to those under 65 years of age. specifically, 30% of those over 75 years of age had gastrointestinal treatment-limiting adverse events compared to 17% of those under 65 years of age. constipation resulted in discontinuation of treatment in 10% of those over 75. 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 tramadol hydrochloride tablets slowly in geriatric patients starting at the low end of the dosing range and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.12)] . tramadol 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. impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, m1. in patients with creatinine clearances of less than 30 ml/min, dosing reduction is recommended [see dosage and administration ( 2.3)] . metabolism of tramadol and m1 is reduced in patients with severe hepatic impairment based on a study in patients with advanced cirrhosis of the liver. in patients with severe hepatic impairment, dosing reduction is recommended [see dosage and administration ( 2.3)] . with the prolonged half-life in these conditions, achievement of steady-state is delayed, so that it may take several days for elevated plasma concentrations to develop. tramadol hydrochloride tablets contain tramadol, a schedule iv controlled substance. tramadol hydrochloride tablets contain tramadol, a substance with 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 tramadol hydrochloride tablets 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 tramadol hydrochloride tablets with alcohol and 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 tramadol hydrochloride tablets abuse include those with a history of prolonged use of any opioid, including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride tablets 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. tramadol hydrochloride 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 tramadol hydrochloride tablets abuse of tramadol hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of tramadol hydrochloride tablets with alcohol and/or other cns depressants. tramadol hydrochloride tablets are approved for oral use only. 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. do not abruptly discontinue tramadol hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride 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 tramadol hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride 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 an extended period of time 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 ( 2.5), warnings and precautions ( 5.18)] . 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)

teva pharmaceuticals usa, inc. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j) - tramadol hydrochloride 50 mg - tramadol hydrochloride tablets are indicated in adults 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 tramadol hydrochloride 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. tramadol hydrochloride tablets 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. tramadol hydrochloride tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.6)] . - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions (5.6)] . tramadol hydrochloride tablets are also 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 (5.12)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.16)] . - hypersensitivity to tramadol, any other component of this product or opioids [see warnings and precautions (5.17)] . - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions (7)] . 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 tramadol hydrochloride tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, tramadol administration during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd). tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the mrhd [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome can present 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 and signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported during postmarketing. 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. tramadol hydrochloride tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including tramadol hydrochloride 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. tramadol has been shown to cross the placenta. the mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. the effect of tramadol hydrochloride tablets, if any, on the later growth, development, and functional maturation of the child is unknown. data animal data tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. these doses on a mg/m2 basis are 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd) for mouse, rat and rabbit, respectively. no drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. embryo and fetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. the dosages listed for mouse, rat and rabbit are 1.7, 1.9 and 14.6 times the mrhd, respectively. tramadol was evaluated in pre- and post-natal studies in rats. progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (1.2 times the mrhd) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (1.9 times the mrhd). risk summary tramadol hydrochloride tablets are not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. tramadol and its metabolite, o -desmethyltramadol (m1), are present in human milk. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the m1 metabolite is more potent than tramadol in mu opioid receptor binding [see clinical pharmacology (12)] . published studies have reported tramadol and m1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of m1, potentially leading to higher levels of m1 in breast milk that can be dangerous in their breastfed infants. in women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. 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 tramadol hydrochloride tablets [see warnings and precautions (5.6)] . clinical considerations if infants are exposed to tramadol hydrochloride through breast milk, they should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. data following a single iv 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of m1. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2)] . the safety and effectiveness of tramadol hydrochloride tablets in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions (5.6)] . in some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. because of the risk of life-threatening respiratory depression and death: - tramadol hydrochloride tablets are contraindicated for all children younger than 12 years of age [see contraindications (4)] . - tramadol hydrochloride tablets are contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see contraindications (4)] . avoid the use of tramadol hydrochloride tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. a total of 455 elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride tablets in controlled clinical trials. of those, 145 subjects were 75 years of age and older. in studies including geriatric patients, treatment-limiting adverse events were higher in subjects over 75 years of age compared to those under 65 years of age. specifically, 30% of those over 75 years of age had gastrointestinal treatment-limiting adverse events compared to 17% of those under 65 years of age. constipation resulted in discontinuation of treatment in 10% of those over 75. 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 tramadol hydrochloride tablets slowly in geriatric patients starting at the low end of the dosing range and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.12)] . tramadol 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. impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, m1. in patients with creatinine clearances of less than 30 ml/min, dosing reduction is recommended [see dosage and administration (2.3)] . metabolism of tramadol and m1 is reduced in patients with severe hepatic impairment based on a study in patients with advanced cirrhosis of the liver. in patients with severe hepatic impairment, dosing reduction is recommended [see dosage and administration (2.3)] . with the prolonged half-life in these conditions, achievement of steady-state is delayed, so that it may take several days for elevated plasma concentrations to develop. tramadol hydrochloride tablets contain tramadol, a schedule iv controlled substance. tramadol hydrochloride tablets contain tramadol, a substance with 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 tramadol hydrochloride tablets 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 tramadol hydrochloride tablets with alcohol and 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 tramadol hydrochloride tablets abuse include those with a history of prolonged use of any opioid, including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride tablets 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. tramadol hydrochloride 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 tramadol hydrochloride tablets abuse of tramadol hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of tramadol hydrochloride tablets with alcohol and/or other cns depressants. tramadol hydrochloride tablets are approved for oral use only. 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. do not abruptly discontinue tramadol hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride 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 tramadol hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride 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 an extended period of time 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 (2.5), warnings and precautions (5.18)] . 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)

collegium pharmaceutical, inc. - oxycodone (unii: cd35pmg570) (oxycodone - unii:cd35pmg570) - oxycodone 9 mg - xtampza er is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations, [see warnings and precautions (5.1)], reserve xtampza er 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. - xtampza er is not indicated as an as-needed (prn) analgesic. xtampza er is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.8)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] - hypersensitivity (e.g., anaphylaxis) to oxycodone. 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)] . there are no available data with xtampza er in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, there was no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the period of organogenesis, at doses 1.3 to 40 times the adult human dose of 60 mg/day, respectively. in a pre- and postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup body weight during lactation and the early post-weaning period at the dose equivalent to an adult dose of 160 mg/day. in several published studies, treatment of pregnant rats with oxycodone hydrochloride at clinically relevant doses and below resulted in neurobehavioral effects in offspring [see data]. 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 of use, and severity of neonatal opioid withdrawal syndrome may 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. xtampza er is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including xtampza er, 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 dilatation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data studies with oral doses of oxycodone hydrochloride in rats up to 8 mg/kg/day and rabbits up to 125 mg/kg/day, equivalent to 1.3 and 40 times an adult human dose of 160 mg/day, respectively on a mg/m2 basis, did not reveal evidence of harm to the fetus due to oxycodone. in a pre- and postnatal toxicity study, female rats received oxycodone during gestation and lactation. there were no drug-related effects on reproductive performance in these females or any long-term developmental or reproductive effects in pups born to these rats. decreased body weight was found during lactation and the early post-weaning phase in pups nursed by dams given the highest dose used (6 mg/kg/day, equivalent to an adult human dose of 160 mg/day, on a mg/m2 basis). however, body weight of these pups recovered. in published studies, offspring of pregnant rats administered oxycodone hydrochloride during gestation have been reported to exhibit neurobehavioral effects including altered stress responses and increased anxiety-like behavior (2 mg/kg/day iv from gestation day 8 to 21 and postnatal day 1, 3, and 5; 0.3-times an adult human oral dose of 60 mg/day on a mg/m2 basis), and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human oral dose of 60 mg/day on a mg/m2 basis). risk summary oxycodone is present in breast milk. published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. the lactation studies did not assess breastfed infants for potential adverse reactions. lactation studies have not been conducted with extended–release oxycodone, including xtampza er, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with xtampza er. clinical considerations monitor infants exposed to xtampza er 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 (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. safety and effectiveness of xtampza er in pediatric patients below the age of 18 years have not been established. in controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see clinical pharmacology (12.3)] . of the total number of subjects entered into the titration phase of the phase 3 study for xtampza er (740), 88 (12%) were age 65 and older. in this clinical trial with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received xtampza er. thus, the usual doses and dosing intervals may be appropriate for elderly patients. 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, concomitant disease, and use of other drug therapy. respiratory depression is the chief risk in 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 xtampza er slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)] . a study in patients with hepatic impairment demonstrated greater plasma oxycodone concentrations than those seen at equivalent doses in persons with normal hepatic function. a similar effect on plasma oxycodone concentrations can be expected for patients with hepatic impairment taking xtampza er. therefore, in the setting of hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration. use of alternative analgesics is recommended for patients who require a dose of xtampza er less than 9 mg [see dosage and administration (2.4), clinical pharmacology (12.3)] . in patients with renal impairment, as evidenced by decreased creatinine clearance (<60 ml/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function. follow a conservative approach to dose initiation and adjust according to the clinical situation. use of alternative analgesics is recommended for patients who require a dose of xtampza er less than 9 mg [see clinical pharmacology (12.3)] . in pharmacokinetic studies with xtampza er, healthy female subjects demonstrate up to 20% higher oxycodone plasma exposures than males, even after considering differences in body weight or bmi. the clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages. in the phase 3 clinical trial there was a greater frequency of typical opioid adverse events for females than males; there was no male/female difference detected for efficacy. xtampza er contains oxycodone, a schedule ii controlled substance. xtampza er contains oxycodone, 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 xtampza er 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 xtampza er 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 xtampza er abuse include those with a history of prolonged use of any opioid, including products containing buprenorphine, those with a history of drug or alcohol abuse, or those who use xtampza er 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. xtampza er, 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 xtampza er abuse of xtampza er poses a risk of overdose and death. the risk is increased with concurrent use of xtampza er with alcohol and/or other cns depressants [see warnings and precautions (5.1, 5.3), drug interactions (7)] . xtampza er is approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. abuse deterrence studies xtampza er capsules contain microspheres formulated with inactive ingredients intended to make the formulation more difficult to manipulate for misuse and abuse. in vitro testing in vitro physical and chemical manipulation studies were performed to evaluate the success of different methods of defeating the extended-release formulation. results support that, relative to immediate-release oxycodone tablets, xtampza er is less susceptible to the effects of grinding, crushing, and extraction using a variety of tools and solvents. xtampza er resisted attempts to pass the melted capsule contents or the microspheres suspended in water through a hypodermic needle. pharmacokinetic studies the pharmacokinetic profile of manipulated xtampza er capsule contents (36 mg; [equivalent to 40 mg oxycodone hcl]) was characterized following oral (three studies) and intranasal (two studies) administration. the studies were conducted in a randomized, cross-over design. in studies assessing manipulation by crushing, the most effective crushing method identified in previous in vitro studies was applied to the product(s). oral pharmacokinetic studies, manipulated and intact xtampza er the effect of two types of product manipulation (crushing and chewing) on xtampza er pharmacokinetics was measured in three studies. in one oral pharmacokinetic study, xtampza er capsule contents were crushed or chewed prior to oral administration in healthy, naltrexone-blocked volunteers. the two comparators in this study were intact xtampza er capsules and an immediate-release solution of oxycodone at an equivalent dose. in two oral pharmacokinetic studies, xtampza er capsule contents were crushed prior to oral administration in healthy, naltrexone-blocked volunteers. the comparators in these studies included intact xtampza er capsules, intact and crushed reformulated oxycontin (oxycodone hydrochloride) extended-release tablets at an equivalent dose, and crushed immediate-release oxycodone tablets at an equivalent dose. the data displayed in table 3 illustrate the findings from the oral pharmacokinetic studies (data were similar for the two oral pharmacokinetic studies comparing xtampza er to oxycontin). collectively, the data demonstrated that crushing or chewing xtampza er prior to administration did not increase the maximum observed plasma concentration (cmax ) or total exposure (auc0-inf ) relative to dosing the intact product under fed conditions. relative to immediate-release oxycodone and crushed reformulated oxycontin (oxycodone hydrochloride) extended-release tablets, the cmax for all xtampza er treatments was lower and the tmax longer, consistent with an extended-release profile. nasal pharmacokinetic studies the pharmacokinetic profile following intranasal administration of crushed xtampza er capsule contents was characterized in two clinical studies. in nasal pharmacokinetic study 1, xtampza er capsule contents (36 mg) were crushed and intranasally administered by non-dependent, naltrexone-blocked subjects with a history of nasal abuse of opioids. the two comparators in this study were intact xtampza er capsules (oral) and oxycodone hcl powder (intranasal) at an equivalent dose. in nasal pharmacokinetic study 2, xtampza er capsule contents (36 mg) were crushed and intranasally administered by non-dependent subjects with a history of nasal abuse of opioids. the two comparators in this study were intact xtampza er capsules (oral) and crushed oxycodone immediate-release tablets (intranasal) at an equivalent dose. the results of nasal pharmacokinetic studies 1 and 2 are comparable and both studies demonstrated that intranasal administration of crushed xtampza er capsule contents did not result in higher peak plasma concentration (cmax ) or shorter time to peak concentration (tmax ) than taking xtampza er orally. the data from nasal pharmacokinetic study 2 are displayed in table 4 to represent these findings. clinical studies oral abuse potential studies: the oral abuse potential of chewed xtampza er was evaluated in two studies. in a randomized, double-blind, active- and placebo-controlled, single-dose, six-way crossover pharmacodynamic study, 52 non-dependent recreational opioid users received orally-administered active and placebo treatment. the six treatment arms were intact xtampza er (36 mg, fed and fasted); chewed xtampza er (36 mg, fed and fasted); crushed immediate-release (ir) oxycodone hcl in solution (40 mg, fasted, equivalent to 36 mg of xtampza er), and placebo. data for chewed and intact xtampza er and crushed ir oxycodone in the fasted state are described below. drug liking was measured on a bipolar 100-point visual analog scale (vas) where 50 represents a neutral response, 0 represents maximum disliking, and 100 represents maximum liking. response to whether the subject would take the study drug again was also measured on a bipolar 100-point vas where 50 represents a neutral response, 0 represents the strongest negative response (e.g., 'definitely would not take drug again'), and 100 represents the strongest positive response (e.g., 'definitely would take drug again'). fifty-two subjects completed the study, and the results are summarized in table 5. the oral administration of chewed and intact xtampza er in the fasted state was associated with statistically lower mean drug liking and take drug again vas scores compared with crushed immediate-release oxycodone. in addition, the drug liking and take drug again scores were similar for xtampza er taken in the intact and chewed states. a prior, similarly-designed study was also conducted to evaluate the oral abuse potential of chewed xtampza er. although the oral administration of chewed and intact xtampza er in the fasted state was associated with statistically lower mean drug liking scores compared with crushed immediate-release oxycodone, the results for take drug again showed small differences that were not statistically significant. nasal abuse potential study: in a randomized, double-blind, active- and placebo-controlled, single-dose, four-way crossover pharmacodynamic study, 39 recreational opioid users with a history of intranasal drug abuse received nasally administered active and placebo drug treatment. the four treatment arms were crushed xtampza er 36 mg dosed intranasally; intact xtampza er 36 mg dosed orally; crushed immediate-release oxycodone hcl 40 mg (equivalent to 36 mg of xtampza er) dosed intranasally; and placebo. data for intranasal xtampza er and crushed immediate-release oxycodone are described below. thirty-six subjects completed the study. intranasal administration of crushed xtampza er was associated with statistically lower mean drug liking and take drug again scores compared with crushed immediate-release oxycodone (summarized in table 6). figure 1 demonstrates a comparison of drug liking for intranasal administration of crushed xtampza er compared to crushed immediate-release oxycodone in subjects who received both treatments (n=36). the y-axis represents the percent of subjects attaining a percent reduction in drug liking for xtampza er vs. immediate-release oxycodone greater than or equal to the value on the x-axis. approximately 92% (n = 33) of subjects had some reduction in drug liking with xtampza er relative to crushed immediate-release oxycodone hcl. approximately 78% (n = 28) of subjects had a reduction of at least 30% in drug liking with xtampza er compared to crushed immediate-release oxycodone hcl, and approximately 58% (n = 21) of subjects had a reduction of at least 50% in drug liking with xtampza er compared to crushed immediate-release oxycodone hcl. figure 1: percent reduction profiles for emax of drug liking vas for crushed xtampza er vs. crushed immediate-release oxycodone, n=36 following intranasal administration summary the in vitro data demonstrate that xtampza er has physicochemical properties expected to make abuse by injection difficult. the data from pharmacokinetic and human abuse potential studies, along with support from the in vitro data, also indicate that xtampza er has physicochemical properties that are expected to reduce abuse via the oral and intranasal routes. the data from the oral pharmacokinetic studies of crushed or chewed xtampza er demonstrated a lack of dose dumping with no increase in oxycodone levels compared to intact xtampza er. however, abuse of xtampza er by injection and by the oral and nasal routes of administration is still possible. additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of xtampza er on the abuse liability of the drug. accordingly, this section may be updated in the future as appropriate. xtampza er contains oxycodone, an opioid agonist and schedule ii controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. xtampza er can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1) and drug abuse and dependence (9.3)] . 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. do not abruptly discontinue xtampza er in a patient physically dependent on opioids. rapid tapering of xtampza er 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 xtampza er, gradually taper the dosage using a patient-specific plan that considers the following: the dose of xtampza er 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 an extended period of time 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 (5.14) ]. 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) ]. always take xtampza er with approximately the same amount of food. if you cannot swallow xtampza er capsules, tell your healthcare provider. if your healthcare provider tells you that you can take xtampza er by sprinkling the capsule contents, follow these steps: xtampza er can be opened and the contents inside the capsule can be sprinkled onto soft foods (such as, applesauce, pudding, yogurt, ice cream, or jam) as follows: - open the xtampza er capsule and sprinkle the contents over about one tablespoon of the soft food listed above (see figure 1). - swallow all of the soft food and sprinkled capsule contents right away. do not save any of the soft food and capsule contents for another dose (see figure 2). - rinse your mouth to make sure you have swallowed all of the capsule contents. (see figure 3). - flush the empty capsule down the toilet right away (see figure 4). xtampza er capsule contents can also be sprinkled into a cup and then put directly into the mouth. giving xtampza er through a nasogastric or gastrostomy tube: use water, milk, or a liquid nutritional supplement to flush the tube when giving xtampza er. this instruction for use has been approved by the u.s. food and drug administration. issued: december 2023 collegium® pharmaceutical