संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

general injectables & vaccines, inc. - naloxone hydrochloride (unii: f850569pqr) (naloxone - unii:36b82amq7n) - naloxone hydrochloride 1 mg in 1 ml - naloxone hydrochloride injection is indicated for the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone and certain narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. naloxone hydrochloride is also indicated for the diagnosis of suspected acute opioid overdosage. naloxone hydrochloride injection may be useful as an adjunctive agent to increase blood pressure in the management of septic shock. naloxone hydrochloride injection is contraindicated in patients known to be hypersensitive to it.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

tagi pharma, inc. - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 8 mg - hydromorphone hydrochloride tablets, usp 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 hydromorphone hydrochloride tablets, usp 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 hydromorphone hydrochloride tablets, usp are contraindicated in patients with: •  significant respiratory depression [see warnings and precautions (5.6)] • acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] • known or suspected gastrointestinal obstruction, including paralyti

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

par pharmaceutical - 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 war

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

unit dose services - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j) - tramadol hydrochloride 300 mg - tramadol hydrochloride extended-release tablets is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)], reserve tramadol hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - tramadol hydrochloride extended-release tablets is not indicated as an as-needed (prn) analgesic. tramadol hydrochloride extended-release tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.3)] - post-operat

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

teva pharmaceuticals usa, inc. - meperidine hydrochloride (unii: n8e7f7q170) (meperidine - unii:9e338qe28f) - meperidine hydrochloride 50 mg - meperidine 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 (5.2)] , reserve meperidine 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. meperidine hydrochloride tablets should not be used for treatment of chronic pain. prolonged meperidine hydrochloride tablets use may increase the risk of toxicity (e.g. seizures) from the accumulation of the meperidine metabolite, normeperidine. meperidine hydrochloride tablets are contraindicated in patients with: - significant respiratory depression [see warnings and preca

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

major pharmaceuticals - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 20 mg in 1 ml - oxycodone hydrochloride oral solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, [see warnings and precautions (5.2)], reserve oxycodone hydrochloride 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 provided adequate analgesia, or are not expected to provide adequate analgesia oxycodone hydrochloride oral solution is contraindicated in patients with: • significant respiratory depression [see warnings and precautions (5.3)] • acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.7)] • known or suspected gastrointestinal obstruction, including paralytic ileus [see wa

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - 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, which can occur at any dosage or duration, [see warnings and precautions (5.1)], reserve oxymorphone hydrochloride for use in patients for whom alternative treatment options continue to be inadequate (e.g., non-opioid analgesics or opioid combination products): oxymorphone hydrochloride 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. oxymorphone hydrochloride is contraindicated in patients with: risk summary: use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions(5.4) and clinical considerations]. data from randomized controlled trials with oxymorphone use in pregnant women during labor and delivery have been conducted. however, these studies were not designed to identify a drug-associated risk for major birth defects and miscarriage because oxymorphone exposure occurred after the first trimester. there are reports of respiratory depression in infants in some of these trials [see clinical considerations]. in animal reproduction studies, reduced postnatal survival of pups and an increased incidence of stillborn pups were observed following oral treatment of pregnant rats with oxymorphone during gestation and through lactation at doses 2.4 and 12 times the human daily dose of 20 mg/day (hdd), respectively. reduced fetal weights were observed with oral administration of oxymorphone to pregnant rats and rabbits during organogenesis at exposures up to 4.9 and 48.8 times the hdd, respectively [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations: fetal/neonatal adverse reactions: use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor or delivery: opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. oxymorphone hydrochloride is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including oxymorphone hydrochloride, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data: animal data: pregnant rats were treated with oxymorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 5, 10, or 25 mg/kg/day (2.4, 4.9, or 12.2 times the hdd based on body surface area, respectively). reduced mean fetal weights were observed at 4.9 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the high dose group). pregnant rabbits were treated with oxymorphone hydrochloride from gestation day 7 to 20 via oral gavage doses of 10, 25, or 50 mg/kg/day (9.8, 24.4, or 48.8 times the hdd based on body surface area, respectively). decreased mean fetal weights were noted at 48.8 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights). pregnant rats were treated with oxymorphone hydrochloride from gestation day 6 to lactation day 20 via oral gavage doses of 1, 5, 10, or 25 mg/kg/day (0.5, 2.4, 4.9, or 12.2 times the hdd based on body surface area, respectively). increased neonatal death (postnatal day 0-1) was noted at 2.4 times the hdd. decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain were noted at 4.9 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the 10 and 25 mg/kg/day groups). in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of 153 mg/kg oxymorphone hydrochloride (62.2 times the hdd) on gestation day 8 to pregnant hamsters. this dose also produced significant maternal toxicity (20% maternal deaths). risk summary: there is no information regarding the presence of oxymorphone in human or animal milk, the effects on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxymorphone hydrochloride and any potential adverse effects on the breastfed child from oxymorphone hydrochloride or from the underlying maternal condition. clinical considerations: monitor infants exposed to oxymorphone hydrochloride through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breast-fed 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 clinical pharmacology (12.2), nonclinical toxicology (13.1)] . safety and effectiveness for pediatric patients, 0 to 17 years, have not been established. an open-label study was conducted in 58 pediatric patients 12 years of age and older with postoperative pain using oxymorphone hydrochloride tablets. efficacy was not demonstrated in this population treated with doses expected to be comparable to effective starting doses in adults. in addition, pharmacokinetic results demonstrated that treatment with oxymorphone hydrochloride tablets resulted in substantially higher systemic exposures to oxymorphone in 2 out of 24 patients. oxymorphone hydrochloride tablets are not recommended for use in the pediatric population. oxymorphone hydrochloride should be used with caution in elderly patients [see clinical pharmacology (12.3)] . of the total number of subjects in clinical studies of oxymorphone hydrochloride, 31% were 65 and over, while 7% were 75 and over. no overall differences in effectiveness were observed between these subjects and younger subjects. there were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. these adverse events included dizziness, somnolence, confusion, and nausea. in general, dose selection for elderly patients should be cautious, 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 oxymorphone hydrochloride slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.3)] . this drug 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. in a study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability compared to the subjects with normal hepatic function. oxymorphone hydrochloride should be used with caution in patients with mild impairment. these patients should be started with the lowest dose (5 mg) and titrated slowly while carefully regularly evaluating for signs of respiratory and central nervous system depression. oxymorphone hydrochloride is contraindicated for patients with moderate and severe hepatic impairment [see dosage and administration (2.4), contraindications (4), warnings and precautions (5.16), and clinical pharmacology (12.3)] . in a study of extended-release oxymorphone tablets, patients with moderate to severe renal impairment were shown to have an increase in bioavailability compared to the subjects with normal renal function [see clinical pharmacology (12.3)] . such patients should be started with the lowest dose (5 mg) and titrated slowly while regularly evaluating for signs of respiratory and central nervous system depression [see dosage and administration (2.5) clinical pharmacology (12.3)] . oxymorphone hydrochloride tablets contain oxymorphone, a schedule ii controlled substance. oxymorphone hydrochloride contains oxymorphone, 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 oxymorphone hydrochloride 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 oxymorphone hydrochloride 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 oxymorphone hydrochloride abuse include those with a history of prolonged use of any opioid, including products containing oxymorphone, those with a history of drug or alcohol abuse, or those who use oxymorphone hydrochloride 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. oxymorphone hydrochloride, 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 oxymorphone hydrochloride: abuse of oxymorphone hydrochloride poses a risk of overdose and death. the risk is increased with concurrent use of oxymorphone hydrochloride 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 oxymorphone hydrochloride in a patient physically dependent on opioids. rapid tapering of oxymorphone hydrochloride 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 oxymorphone hydrochloride, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxymorphone hydrochloride 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 ( 2.9 ), 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)].

ऑस्ट्रेलिया - अंग्रेज़ी - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - naloxone hydrochloride dihydrate, quantity: 440 microgram/ml (equivalent: naloxone hydrochloride?, qty 400 microgram/ml) - injection, solution - excipient ingredients: water for injections; hydrochloric acid - naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by opioids including natural and synthetic opioids, propoxyphene, methadone and the narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. naloxone hydrochloride injection is also indicated for the diagnosis of suspected acute opioid overdosage.

ऑस्ट्रेलिया - अंग्रेज़ी - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - naloxone hydrochloride dihydrate, quantity: 22 microgram/ml (equivalent: naloxone hydrochloride?, qty 20 microgram/ml) - injection, solution - excipient ingredients: water for injections; hydrochloric acid - naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by opioids including natural and synthetic opioids, propoxyphene, methadone and the narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. naloxone hydrochloride injection is also indicated for the diagnosis of suspected acute opioid overdosage.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

american health packaging - 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, even at recommended doses [see warnings and precautions (5.1)] , reserve tramadol hydrochloride 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 provided adequate analgesia or are not expected to provide adequate analgesia. tramadol hydrochloride is contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.4)] . - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions (5.4)] . tramadol hydrochloride is also contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] . - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.12)] . - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings andprecautions (5.15)] . - hypersensitivity to tramadol, any other component of this product or opioids [see warnings andprecautions (5.16)] . - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions (7)] . risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. available data with tramadol hydrochloride 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% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in 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 (5.5)] . 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 is 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, 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, 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 is 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 [see warnings and precautions (5.4)] . 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 chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2)] . the safety and effectiveness of tramadol hydrochloride in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions (5.4)] . 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 is contraindicated for all children younger than 12 years of age [see contraindications (4)] . - tramadol hydrochloride is 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 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 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 slowly in geriatric patients starting at the low end of the dosing range and monitor closely 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 contains tramadol, a schedule iv controlled substance. tramadol hydrochloride tablets contains tramadol, a substance with a high potential for abuse similar to other opioids. tramadol hydrochloride can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)] . all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful, or potentially harmful, consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. tramadol hydrochloride, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of tramadol hydrochloride tramadol hydrochloride is intended for oral use only. abuse of tramadol hydrochloride poses a risk of overdose and death. the risk is increased with concurrent abuse of tramadol hydrochloride with alcohol and other central nervous system depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of drugs to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue tramadol hydrochloride in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride 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, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.5), warnings and precautions (5.17)] . 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)] .