Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - hydrocodone bitartrate (unii: no70w886kk) (hydrocodone - unii:6yks4y3wq7), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - hydrocodone bitartrate 5 mg - hydrocodone bitartrate and acetaminophen tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration (see warnings ), reserve hydrocodone bitartrate and acetaminophen tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): - have not been tolerated, or are not expected to be tolerated, have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia have not provided adequate analgesia, or are not expected to provide adequate analgesia hydrocodone bitartrate and acetaminophen 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. hydrocodone bitartrate and acetaminophen tablets are contraindicated in patients with: - significant respiratory depression (see warnings ) significant respiratory depression (see warnings ) - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see warnings ) acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see warnings ) - known or suspected gastrointestinal obstruction, including paralytic ileus (see warnings ) known or suspected gastrointestinal obstruction, including paralytic ileus (see warnings ) - hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) (see warnings  and adverse reactions ) hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) (see warnings  and adverse reactions ) hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, a schedule ii controlled substance. hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction (see warnings ). 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 hydrocodone bitartrate and acetaminophen 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 hydrocodone bitartrate and acetaminophen 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 hydrocodone bitartrate and acetaminophen tablets abuse include those with a history of prolonged use of any opioid, including products containing hydrocodone, those with a history of drug or alcohol abuse, or those who use hydrocodone bitartrate and acetaminophen 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. hydrocodone bitartrate and acetaminophen 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 hydrocodone bitartrate and acetaminophen tablets abuse of hydrocodone bitartrate and acetaminophen tablets poses a risk of overdose and death. the risk is increased with concurrent use of hydrocodone bitartrate and acetaminophen tablets with alcohol and/or other cns depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue hydrocodone bitartrate and acetaminophen tablets in a patient physically dependent on opioids. rapid tapering of hydrocodone bitartrate and acetaminophen tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing hydrocodone bitartrate and acetaminophen tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydrocodone bitartrate and acetaminophen tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for 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, and warnings ).   infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs (see pregnancy ).

Estados Unidos - inglês - NLM (National Library of Medicine)

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

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 7.5 mg - xartemis xr is indicated for the management of acute pain severe enough to require 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 [see warnings and precautions (5.1)] , reserve xartemis xr for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): - have not been tolerated or are not expected to be tolerated, - have not provided adequate analgesia or are not expected to provide adequate analgesia. xartemis xr tablets are contraindicated in patients with - significant respiratory depression [see warnings and precautions (5.2)] significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipmen

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - oxymorphone hydrochloride (unii: 5y2ei94nbc) (oxymorphone - unii:9vxa968e0c) - oxymorphone hydrochloride 5 mg - oxymorphone hydrochloride tablets are indicated for the management of acute 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 oxymorphone 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 oxymorphone hydrochloride 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)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see w

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 8 mg - exalgo is indicated for the management of pain in opioid-tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. patients considered opioid tolerant are those who are receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. 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 exalgo 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. because of the risks

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - temazepam (unii: chb1qd2qss) (temazepam - unii:chb1qd2qss) - temazepam 7.5 mg - restoril™ (temazepam) is indicated for the short-term treatment of insomnia (generally 7 to 10 days). for patients with short-term insomnia, instructions in the prescription should indicate that restoril™ (temazepam) should be used for short periods of time (7 to 10 days). the clinical trials performed in support of efficacy were 2 weeks in duration with the final formal assessment of sleep latency performed at the end of treatment. restoril contains temazepam, a schedule iv controlled substance. restoril is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. 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. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 20 mg in 1 ml - morphine sulfate oral solution 100 mg per 5 ml (20 mg/ml) is indicated for the relief of acute and chronic pain in opioid-tolerant adult patients . limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.2)] , reserve morphine sulfate oral solution 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 been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia. have not provided adequate analgesia, or are not expected to provide adequate analgesia. pediatric use information is approved for hikma pharmaceuticals usa inc.’s morphine sulfate oral solution. however, due to hikma pharmaceuticals usa inc.’s marketing exclusivity rights, this drug product is not labeled with that information. morphine

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 5 mg - oxycodone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve oxycodone 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. oxycodone hydrochloride 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 or hypercarbia [ see warnings and precautions (5.7) ] . - known or suspected gastrointestinal obstruction, including paralytic ileu

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - methadone hydrochloride (unii: 229809935b) (methadone - unii:uc6vbe7v1z) - methadone hydrochloride 5 mg - methadone hydrochloride tablets are indicated for the: 1.     management of severe and persistent pain that requires an extended treatment period with 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 [see warnings and precautions (5.1)] , reserve methadone hydrochloride tablets for use in patients for whom alternative analgesic treatment options (e.g., non-opioid analgesics or immediate-release opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. 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 methadone hydrochloride tablets for use in patients for whom alternative analgesic treatment options (e.g., non-opioid analgesics or immediate-release opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - methadone hydrochloride tablets are not indicated as an as-needed (prn) analgesic. methadone hydrochloride tablets are not indicated as an as-needed (prn) analgesic. 2.     detoxification treatment of opioid addiction (heroin or other morphine-like drugs). 3.     maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services. limitations of use methadone products used for the treatment of opioid addiction in detoxification or maintenance programs are subject to the conditions for distribution and use required under 42 cfr 8.12 [see dosage and administration (2.1)] . methadone hydrochloride 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 (5.10)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.14)] . - hypersensitivity (e.g., anaphylaxis) to methadone [see adverse reactions (6)] . risk summary the majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. pregnant women involved in methadone maintenance programs have been reported to have improved prenatal care leading to reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. several factors, including maternal use of illicit drugs, nutrition, infection and psychosocial circumstances, complicate the interpretation of investigations of the children of women who take methadone during pregnancy. information is limited regarding dose and duration of methadone use during pregnancy, and most maternal exposure in these studies appears to occur after the first trimester of pregnancy (see data ). neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of use of opioids for an extended period of time during pregnancy [see warnings and precautions (5.5)]. in published animal reproduction studies, methadone administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) in the hamster at doses 2 times the human daily oral dose of 120 mg/day on a mg/m2 basis (hdd) and in mice at doses equivalent to the hdd. administration of methadone to pregnant animals during organogenesis and through lactation resulted decreased litter size, increased pup mortality, decreased pup body weights, developmental delays, 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. administration of methadone to male rodents prior to mating with untreated females resulted in increased neonatal mortality and significant differences in behavioral tests in the offspring at exposures comparable to and less than the hdd (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% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and embryo-fetal risk : untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. dosage adjustment during pregnancy : dosage adjustment using higher doses or administering the daily dose in divided doses may be necessary in pregnant women treated with methadone hydrochloride tablets. pregnant women appear to have significantly lower trough plasma methadone concentrations, increased plasma methadone clearance, and shorter methadone half-life than after delivery [see dosage and administration (2.9) and clinical pharmacology (12.3)] . withdrawal signs and symptoms should be closely monitored and the dose adjusted as necessary. fetal/neonatal adverse reactions : neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with methadone hydrochloride tablets. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. signs of neonatal withdrawal usually occur in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)] . labor or delivery : opioid-dependent women on methadone maintenance therapy may require additional analgesia during labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data : the majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. findings regarding specific major malformations, decreased fetal growth, premature birth and sudden infant death syndrome have been inconsistent. children prenatally exposed to methadone have been reported to demonstrate mild but persistent deficits in performance on psychometric and behavioral tests and visual abnormalities. in a multicenter, double-blind, randomized, controlled trial [maternal opioid treatment: human experimental research (mother)] designed primarily to assess neonatal opioid withdrawal effects, opioid-dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. a total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. among women who remained in treatment until delivery, there was no difference between methadone-treated and buprenorphine-treated groups in the number of neonates requiring nows treatment or in the peak severity of nows. buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs. 10.4 mg), had shorter hospital stays (10.0 days vs. 17.5 days), and shorter duration of treatment for nows (4.1 days vs. 9.9 days) compared to the methadone-exposed group. there were no differences between groups in other primary outcomes (neonatal head circumference), or secondary outcomes (weight and length at birth, preterm birth, gestational age at delivery, and 1-minute and 5-minute apgar scores), or in the rates of maternal or neonatal adverse events. the outcomes among mothers who discontinued treatment before delivery and may have relapsed to illicit opioid use are not known. because of the imbalance in discontinuation rates between the methadone and buprenorphine groups, the study findings are difficult to interpret. animal data : formal reproductive and developmental toxicology studies for methadone have not been conducted. exposure margins for the following published study reports are based on a human daily dose (hdd) of 120 mg methadone using a body surface area comparison. in a published study in pregnant hamsters, a single subcutaneous dose of methadone ranging from 31 mg/kg (2 times the hdd) to 185 mg/kg on gestation day 8 resulted in a decrease in the number of fetuses per litter and an increase in the percentage of fetuses exhibiting neural tube defects including exencephaly, cranioschisis, and "various other lesions." the majority of the doses tested also resulted in maternal death. in a study in pregnant jbt/jd mice, a single subcutaneous dose of 22 to 24 mg/kg methadone (approximately equivalent to the hdd) administered on gestation day 9 produced exencephaly in 11% of the embryos. in another study in pregnant mice, subcutaneous doses up to 28 mg/kg/day methadone (equivalent to the hdd) administered from gestation day 6 to 15 resulted in no malformations, but there were increased postimplantation loss and decreased live fetuses at 10 mg/kg/day or greater (0.4 times the hdd) and decreased ossification and fetal body weight at 20 mg/kg/day or greater (0.8 times the hdd). in a second study of pregnant mice dosed with subcutaneous doses up to 28 mg/kg/day methadone from gestation day 6 to 15, there was decreased pup viability, delayed onset of development of negative phototaxis and eye opening, increased righting reflexes at 5 mg/kg/day or greater (0.2 times the hdd), and decreased number of live pups at birth and decreased pup weight gain at 20 mg/kg/day or greater (0.8 times the hdd). no effects were reported in a study of pregnant rats and rabbits at oral doses up to 40 mg/kg (3 and 6 times, respectively, the hdd) administered from gestation days 6 to 15 and 6 to 18, respectively. when pregnant rats were treated with intraperitoneal doses of 2.5, 5, or 7.5 mg/kg methadone from one week prior to mating, through gestation until the end of lactation period, 5 mg/kg or greater (0.4 times the hdd) methadone resulted in decreases in litter size and live pups born and 7.5 mg/kg (0.6 times the hdd) resulted in decreased birth weights. furthermore, decreased pup viability and pup body weight gain at 2.5 mg/kg or greater (0.2 times the hdd) were noted during the preweaning period. additional animal data demonstrate evidence for neurochemical changes in the brains of offspring from methadone-treated pregnant rats, including changes to the cholinergic, dopaminergic, noradrenergic and serotonergic systems at doses below the hdd. other animal studies have reported that prenatal and/or postnatal exposure to opioids including methadone alters neuronal development and behavior in the offspring including alterations in learning ability, motor activity, thermal regulation, nociceptive responses, and sensitivity to drugs at doses below the hdd. treatment of pregnant rats subcutaneously with 5 mg/kg methadone from gestation day 14 to 19 (0.4 times the hdd) reduced fetal blood testosterone and androstenedione in males. published animal data have reported increased neonatal mortality in the offspring of male rodents that were treated with methadone at doses comparable to and less than the hdd for 1 to 12 days before and/or during mating (with more pronounced effects in the first 4 days). in these studies, the female rodents were not treated with methadone, indicating paternally-mediated developmental toxicity. specifically, methadone administered to the male rat prior to mating with methadone-naïve females resulted in decreased weight gain in progeny after weaning. the male progeny demonstrated reduced thymus weights, whereas the female progeny demonstrated increased adrenal weights. behavioral testing of these male and female progeny revealed significant differences in behavioral tests compared to control animals, suggesting that paternal methadone exposure can produce physiological and behavioral changes in progeny in this model. examination of uterine contents of methadone-naïve female mice bred to methadone-treated male mice (once a day for three consecutive days) indicated that methadone treatment produced an increase in the rate of preimplantation deaths in all post-meiotic states at 1 mg/kg/day or greater (0.04 times the hdd). chromosome analysis revealed a dose-dependent increase in the frequency of chromosomal abnormalities at 1 mg/kg/day or greater. studies demonstrated that methadone treatment of male rats for 21 to 32 days prior to mating with methadone-naïve females did not produce any adverse effects, suggesting that prolonged methadone treatment of the male rat resulted in tolerance to the developmental toxicities noted in the progeny. mechanistic studies in this rat model suggest that the developmental effects of "paternal" methadone on the progeny appear to be due to decreased testosterone production. these animal data mirror the reported clinical findings of decreased testosterone levels in human males on methadone maintenance therapy for opioid addiction and in males receiving chronic intraspinal opioids. risk summary based on two small clinical studies, methadone was present in low levels in human milk, but the exposed infants in these studies did not show adverse reactions. based on an average milk consumption of 150 ml/kg/day, an infant would consume approximately 17.4 mcg/kg/day which is approximately 2% to 3% of the oral maternal dose. there have been rare case reports of sedation and respiratory depression in infants exposed to methadone through breast milk (see data ). monitor infants exposed to methadone hydrochloride tablets through breast milk for excess sedation and respiratory depression. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for methadone and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. data in a study of ten breastfeeding women maintained on oral methadone doses of 10 to 80 mg/day, methadone concentrations from 50 to 570 mcg/l in milk were reported, which, in the majority of samples, were lower than maternal serum drug concentrations at steady state. peak methadone levels in milk occur approximately 4 to 5 hours after an oral dose. in a study of twelve breastfeeding women maintained on oral methadone doses of 20 to 80 mg/day, methadone concentrations from 39 to 232 mcg/l in milk were reported. based on an average milk consumption of 150 ml/kg/day, an infant would consume approximately 17.4 mcg/kg/day, which is approximately 2% to 3% of the oral maternal dose. methadone has been detected in very low plasma concentrations in some infants whose mothers were taking methadone. infertility the effect of methadone hydrochloride tablets on fertility is unknown. use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6), clinical pharmacology (12.2), nonclinical pharmacology (13.1)] . reproductive function in human males may be decreased by methadone treatment. reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals. in addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported. in published animal studies, methadone produces a significant regression of sex accessory organs and testes of male mice and rats and administration of methadone to pregnant rats reduced fetal blood testosterone and androstenedione in male offspring [see nonclinical toxicology (13)] . the safety, effectiveness, and pharmacokinetics of methadone in pediatric patients below the age of 18 years have not been established. clinical studies of methadone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects. other reported clinical experience has not identified differences in responses between elderly and younger patients. elderly patients (aged 65 years or older) may have increased sensitivity to methadone. 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 methadone hydrochloride tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.10)] . methadone 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. methadone pharmacokinetics have not been extensively evaluated in patients with hepatic insufficiency. methadone is metabolized by hepatic pathways; therefore, patients with liver impairment may be at risk of increased systemic exposure to methadone after multiple dosing. start these patients on lower doses and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression. methadone pharmacokinetics have not been extensively evaluated in patients with renal insufficiency. since unmetabolized methadone and its metabolites are excreted in urine to a variable degree, start these patients on lower doses and with longer dosing intervals and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression. methadone hydrochloride tablets contain methadone, a schedule ii controlled substance. methadone hydrochloride tablets contain methadone, a substance with a 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 methadone 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 methadone 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 methadone hydrochloride tablets abuse include those with a history of prolonged use of any opioid, including products containing methadone, those with a history of drug or alcohol abuse, or those who use methadone 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. methadone 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 methadone hydrochloride tablets abuse of methadone hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of methadone hydrochloride tablets with alcohol and/or other cns depressants. methadone hydrochloride tablets are approved for oral use only. inappropriate intravenous, intramuscular, or subcutaneous use of methadone hydrochloride tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. 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 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 methadone hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of methadone 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 methadone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of methadone 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 (2.6), and warnings and precautions (5.16)] . 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)].

Estados Unidos - inglês - NLM (National Library of Medicine)

specgx llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 5 mg - roxicodone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions (5.1)] , reserve roxicodone 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. roxicodone 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. roxicodone is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] . 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 or hypercarbia [see warnings and precautions (5.8)] . acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment or hypercarbia [see warnings and precautions (5.8)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] . known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] . - known hypersensitivity (e.g., anaphylaxis) to oxycodone [see adverse reactions (6.2)]. known hypersensitivity (e.g., anaphylaxis) to oxycodone [see adverse reactions (6.2)]. 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 roxicodone in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. animal reproduction studies with oral administrations of oxycodone hcl in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. in several published studies, treatment of pregnant rats with oxycodone 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. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the 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 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 use, 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. roxicodone is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including roxicodone, can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data in embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone hcl administered during the period of organogenesis up to 16 mg/kg/day and up to 25 mg/kg/day, respectively. these studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. the highest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day, respectively, on a mg/m2 basis. in published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, 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 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 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 roxicodone, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for roxicodone and any potential adverse effects on the breastfed infant from roxicodone or from the underlying maternal condition. clinical considerations monitor infants exposed to roxicodone 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 breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2)] . the safety and efficacy of roxicodone in pediatric patients have not been evaluated. of the total number of subjects in clinical studies of roxicodone, 20.8% (112/538) were 65 and over, while 7.2% (39/538) were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. 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 roxicodone slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.2)] . oxycodone 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 regularly evaluate renal function. because oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. initiate therapy in these patients with a lower than usual dosage of roxicodone and titrate carefully. regularly evaluate for adverse events such as respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)] . because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with renal impairment. initiate therapy with a lower than usual dosage of roxicodone and titrate carefully. regularly evaluate  for adverse events such as respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)] . roxicodone contains oxycodone, a schedule ii controlled substance. roxicodone 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 roxicodone 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 roxicodone 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 roxicodone abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use roxicodone 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. roxicodone, 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 roxicodone abuse of roxicodone poses a risk of overdose and death. the risk is increased with concurrent use of roxicodone with alcohol and/or other cns depressants. roxicodone is 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 roxicodone in a patient physically dependent on opioids. rapid tapering of roxicodone 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 roxicodone, gradually taper the dosage using a patient-specific plan that considers the following: the dose of roxicodone 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 (2.4), and 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)] .