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

rhodes pharmaceuticals l.p. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - buprenorphine 5 ug in 1 h - buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse and misuse with opioids, which can occur at any dosage or duration, and because of the greater risk of overdose and death with extended- release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve buprenorphine transdermal system 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. - buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic. buprenorphine transdermal system is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.10)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.15)] - hypersensitivity (e.g., anaphylaxis) to buprenorphine [see warnings and precautions (5.18), adverse reactions (6)] 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 buprenorphine transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, buprenorphine caused an increase in the number of stillborn offspring, reduced litter size, and reduced offspring growth in rats at maternal exposure levels that were approximately 10 times that of human subjects who received one buprenorphine transdermal system 20 mcg/hour, the maximum recommended human dose (mrhd) [see data]. based on animal data, advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, 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 and delivery opioids cross the placenta and may produce respiratory depression in neonates. an opioid antagonist such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. buprenorphine transdermal system is not recommended for use in women immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including buprenorphine transdermal system, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. data animal data studies in rats and rabbits demonstrated no evidence of teratogenicity following buprenorphine transdermal system or subcutaneous (sc) administration of buprenorphine during the period of organogenesis. rats were administered up to one buprenorphine transdermal system 20 mcg/hour every 3 days (gestation days 6, 9, 12, & 15) or received daily sc buprenorphine up to 5 mg/kg (gestation days 6 to 17). rabbits were administered four buprenorphine transdermal system 20 mcg/hour every 3 days (gestation days 6, 9, 12, 15, 18, and 19) or received daily sc buprenorphine up to 5 mg/kg (gestation days 6 to 19). no teratogenicity was observed at any dose. auc values for buprenorphine with buprenorphine transdermal system application and sc injection were approximately 110 and 140 times, respectively, that of human subjects who received the mrhd of one buprenorphine transdermal system 20 mcg/hour. in a pre- and post-natal study conducted in pregnant and lactating rats, administration of buprenorphine either as buprenorphine transdermal system or sc buprenorphine was associated with toxicity to offspring. buprenorphine was present in maternal milk. pregnant rats were administered 1/4 of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily sc buprenorphine at doses of 0.05, 0.5, or 5 mg/kg from gestation day 6 to lactation day 21 (weaning). administration of buprenorphine transdermal system or sc buprenorphine at 0.5 or 5 mg/kg caused maternal toxicity and an increase in the number of stillborns, reduced litter size, and reduced offspring growth at maternal exposure levels that were approximately 10 times that of human subjects who received the mrhd of one buprenorphine transdermal system 20 mcg/hour. maternal toxicity was also observed at the no observed adverse effect level (noael) for offspring. risk summary 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 buprenorphine transdermal system. clinical considerations monitor infants exposed to buprenorphine transdermal system through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of buprenorphine is stopped or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), preclinical pharmacology (12.2), nonclinical toxicology (13.1)] . the safety and efficacy of buprenorphine transdermal system in patients under 18 years of age has not been established. buprenorphine transdermal system has been evaluated in an open-label clinical trial in pediatric patients. however, definitive conclusions are not possible because of the small sample size. of the total number of subjects in the clinical trials (5,415), buprenorphine transdermal system was administered to 1,377 patients aged 65 years and older. of those, 457 patients were 75 years of age and older. in the clinical program, the incidences of selected buprenorphine transdermal system-related aes were higher in older subjects. the incidences of application site aes were slightly higher among subjects < 65 years of age than those ≥ 65 years of age for both buprenorphine transdermal system and placebo treatment groups. in a single-dose study of healthy elderly and healthy young subjects treated with buprenorphine transdermal system 10 mcg/hour, the pharmacokinetics were similar. in a separate dose-escalation safety study, the pharmacokinetics in the healthy elderly and hypertensive elderly subjects taking thiazide diuretics were similar to those in the healthy young adults. in the elderly groups evaluated, adverse event rates were similar to or lower than rates in healthy young adult subjects, except for constipation and urinary retention, which were more common in the elderly. although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use [see clinical pharmacology (12.3)] . 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 buprenorphine transdermal system slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.10)] . in a study utilizing intravenous buprenorphine, peak plasma levels (cmax ) and exposure (auc) of buprenorphine in patients with mild and moderate hepatic impairment did not increase as compared to those observed in subjects with normal hepatic function. buprenorphine transdermal system has not been evaluated in patients with severe hepatic impairment. as buprenorphine transdermal system is intended for 7-day dosing, consider the use of alternate analgesic therapy in patients with severe hepatic impairment [see dosage and administration (2.6), clinical pharmacology (12.3)]. buprenorphine transdermal system contains buprenorphine, a schedule iii controlled substance. buprenorphine transdermal system contains buprenorphine, 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 buprenorphine transdermal system 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 buprenorphine transdermal system 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 buprenorphine transdermal system abuse include those with a history of prolonged use of any opioid, including products containing buprenorphine, those with a history of drug or alcohol abuse, or those who use buprenorphine transdermal system 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. buprenorphine transdermal system, 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 buprenorphine transdermal system abuse of buprenorphine transdermal system poses a risk of overdose and death. this risk is increased with the concurrent use of buprenorphine transdermal system with alcohol and/or other substances including other opioids and benzodiazepines [see warnings and precautions (5.1, 5.3), drug interactions (7)] . buprenorphine transdermal system is approved for transdermal use only. intentional compromise of the transdermal delivery system will result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death [see warnings and precautions (5.1)] . abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by chewing, swallowing, snorting, or injecting buprenorphine extracted from the transdermal system. 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 buprenorphine transdermal system in a patient physically dependent on opioids. rapid tapering of buprenorphine transdermal system 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 buprenorphine transdermal system, gradually taper the dosage using a patient-specific plan that considers the following: the dose of buprenorphine transdermal system 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 (2.1), warnings and precautions (5.19)] . 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)] . be sure that you read, understand, and follow these instructions for use before you use buprenorphine transdermal system. talk to your healthcare provider or pharmacist if you have any questions. before applying buprenorphine transdermal system: - do not use soap, alcohol, lotions, oils, or other products to remove any leftover adhesive from a patch because this may cause more buprenorphine transdermal system to pass through the skin. - each patch is sealed in its own protective pouch. do not remove a patch from the pouch until you are ready to use it. - do not use a patch if the seal on the protective pouch is broken or if the patch is cut, damaged, or changed in any way. - buprenorphine transdermal system patches are available in different strengths and patch sizes. make sure you have the right strength patch that has been prescribed for you. where to apply buprenorphine transdermal system: - buprenorphine transdermal system should be applied to the upper outer arm, upper chest, upper back, or the side of the chest (see figure a ). these 4 sites (located on both sides of the body) provide 8 possible buprenorphine transdermal system application sites. - do not apply more than 1 patch at the same time unless your doctor tells you to. however, if your healthcare provider tells you to do so, you may use 2 patches as prescribed, applied at the same site (see figure a for application sites) right next to each other (see figure b for an example of patch position when applying 2 patches). always apply and remove the two patches together at the same time. - you should change the skin site where you apply buprenorphine transdermal system each week, making sure that at least 3 weeks (21 days) pass before you re-use the same skin site. - apply buprenorphine transdermal system to a hairless or nearly hairless skin site . if needed, you can clip the hair at the skin site (see figure c ). do not shave the area. the skin site should not be irritated. use only water to clean the application site. you should not use soaps, alcohol, oils, lotions, or abrasive devices. allow the skin to dry before you apply the patch. - the skin site should be free of cuts and irritation (rashes, swelling, redness, or other skin problems). when to apply a new patch: - when you apply a new patch, write down the date and time that the patch is applied. use this to remember when the patch should be removed. - change the patch at the same time of day, one week (exactly 7 days) after you apply it. - after removing and disposing of the patch, write down the time it was removed and how it was disposed. how to apply buprenorphine transdermal system: - if you are wearing a patch, remember to remove it before applying a new one. - each patch is sealed in its own protective pouch. - if you are using two patches, remember to apply them at the same site right next to each other. always apply and remove the two patches together at the same time. - use scissors to cut open the pouch along the dotted line (see figure d ) and remove the patch. do not remove the patch from the pouch until you are ready to use it. do not use patches that have been cut or damaged in any way. - hold the patch with the protective liner facing you. - gently bend the patch (see figures e and f ) along the faint line and slowly peel the larger portion of the liner, which covers the sticky surface of the patch. - do not touch the sticky side of the patch with your fingers. - using the smaller portion of the protective liner as a handle (see figure g ), apply the sticky side of the patch to one of the 8 body locations described above (see "where to apply buprenorphine transdermal system" ). - while still holding the sticky side down, gently fold back the smaller portion of the patch. grasp an edge of the remaining protective liner and slowly peel it off (see figure h ). - press the entire patch firmly into place with the palm (see figure i ) of your hand over the patch, for about 15 seconds. do not rub the patch. - make sure that the patch firmly sticks to the skin. - go over the edges with your fingers to assure good contact around the patch. - if you are using two patches, follow the steps in this section to apply them right next to each other. - always wash your hands after applying or handling a patch. - after the patch is applied, write down the date and time that the patch is applied. use this to remember when the patch should be removed. if the patch falls off right away after applying, throw it away and put a new one on at a different skin site (see "disposing of buprenorphine transdermal system patch") . if a patch falls off, do not touch the sticky side of the patch with your fingers. a new patch should be applied to a different site. patches that fall off should not be re-applied . they must be thrown away correctly. short-term exposure of the buprenorphine transdermal system patch to water, such as when bathing or showering, is permitted. if the edges of the buprenorphine transdermal system patch start to loosen: - apply first aid tape only to the edges of the patch. - if problems with the patch not sticking continue, cover the patch with special see-through adhesive dressings (for example bioclusive or tegaderm). remove the backing from the transparent adhesive dressing and place it carefully and completely over the buprenorphine transdermal system patch, smoothing it over the patch and your skin. - remove the backing from the transparent adhesive dressing and place it carefully and completely over the buprenorphine transdermal system patch, smoothing it over the patch and your skin. - never cover a buprenorphine transdermal system patch with any other bandage or tape. it should only be covered with a special see-through adhesive dressing. talk to your healthcare provider or pharmacist about the kinds of dressing that should be used. if your patch falls off later, but before 1 week (7 days) of use, throw it away properly (see "disposing of a buprenorphine transdermal system patch") and apply a new patch at a different skin site. be sure to let your healthcare provider know that this has happened. do not replace the new patch until 1 week (7 days) after you put it on (or as directed by your healthcare provider). disposing of buprenorphine transdermal system patch: buprenorphine transdermal system patches should be disposed of by using the patch-disposal unit. alternatively, the patches can be flushed down the toilet if a drug take-back option is not readily available. to dispose of buprenorphine transdermal system patches in household trash using the patch-disposal unit: remove your patch and follow the directions printed on the patch-disposal unit (see figure j ) or see complete instructions below. use one patch-disposal unit for each patch. 1. peel back the disposal unit liner to show the sticky surface (see figure k ). 2. place the sticky side of the used or unused patch to the indicated area on the disposal unit (see figure l ). 3. close the disposal unit by folding the sticky sides together (see figure m ). press firmly and smoothly over the entire disposal unit so that the patch is sealed within. 4. the closed disposal unit, with the patch sealed inside may be thrown away in the trash (see figure n ). do not put expired, unwanted, or unused patches in household trash without first sealing them in the patch-disposal unit. always remove the leftover patches from their protective pouch and remove the protective liner. the pouch and liner can be disposed of separately in the trash and should not be sealed in the patch-disposal unit. to flush your buprenorphine transdermal system patches down the toilet: remove your buprenorphine transdermal system patch, fold the sticky sides of a used patch together and flush it down the toilet right away (see figure o ). when disposing of unused buprenorphine transdermal system patches you no longer need, remove the leftover patches from their protective pouch and remove the protective liner. fold the patches in half with the sticky sides together, and flush the patches down the toilet. do not flush the pouch or the protective liner down the toilet. these items can be thrown away in the trash. if you prefer not to flush the used patch down the toilet , and if there is not a drug take-back option readily available, you must use the patch-disposal unit provided to you to discard the patch. never put used buprenorphine transdermal system patches in the trash without first sealing them in the patch-disposal unit. this "instructions for use" has been approved by the u.s. food and drug administration. marketed by: rhodes pharmaceuticals, wilson, nc 27893 revised: 2/2023 bioclusive is a trademark of systagenix wound management (us), inc. tegaderm is a trademark of 3m.

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

hikma pharmaceuticals usa inc. - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 4 mg - hydromorphone hydrochloride oral solution and hydromorphone 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, which can occur at any dosage or duration [see warnings and precautions (5.2)], reserve hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are contraindicated in patients with: risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)]. there are no available data with hydromorphone hydrochloride in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (hdd), respectively. in published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the hdd and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the hdd to pregnant mice. no malformations were noted at 4 or 40.5 times the hdd in pregnant rats or rabbits, respectively [see data]. based on animal data, advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions : use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)]. labor or delivery : opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data : pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). there was no evidence of malformations or embryotoxicity reported. pregnant rabbits were treated with hydromorphone hydrochloride from gestation day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). there was no evidence of malformations or embryotoxicity reported. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on gestation day 8 to pregnant hamsters (6.4 to 87.2 times the hdd of 24 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. no neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day). in a published study, cf-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (gestation days 7 to 10). soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. the findings cannot be clearly attributed to maternal toxicity. increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from gestation day 7 to lactation day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested. risk summary low levels of opioid analgesics have been detected in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets and any potential adverse effects on the breastfed infant from hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor infants exposed to hydromorphone hydrochloride through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of hydromorphone hydrochloride in pediatric patients have not been established. elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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 hydromorphone hydrochloride slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)]. hydromorphone 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. the pharmacokinetics of hydromorphone is affected by hepatic impairment. due to increased exposure of hydromorphone, patients with hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and regularly evaluated during dose titration. the pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. a further increase in cmax and auc of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see clinical pharmacology (12.3)]. the pharmacokinetics of hydromorphone is affected by renal impairment. in addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life. start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. patients with renal impairment should be regularly evaluated during dose titration [see clinical pharmacology (12.3)]. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a schedule ii controlled substance. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, 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 (5.2)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, 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 hydromorphone 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 hydromorphone hydrochloride 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 hydromorphone hydrochloride abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use hydromorphone 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. hydromorphone 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 hydromorphone hydrochloride abuse of hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of hydromorphone hydrochloride tablets with alcohol and/or other cns depressants. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of hydromorphone hydrochloride oral solution and hydromorphone 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 hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydromorphone hydrochloride oral solution and hydromorphone 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 ( 2.7 ), 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)] .

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aidarex pharmaceuticals llc - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride (unii: f850569pqr) (naloxone - unii:36b82amq7n) - buprenorphine 8 mg - buprenorphine and naloxone sublingual tablets are indicated for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support. under the drug addiction treatment act (data) codified at 21 u.s.c. 823(g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the secretary of health and human services (hhs) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription. buprenorphine and naloxone sublingual tablets should not be administered to patients who have been shown to be hypersensitive to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.8)] . pregnancy category c. risk summary there are no adequate and well-contr

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mylan pharmaceuticals inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz) - buprenorphine 2 mg - buprenorphine sublingual tablets are indicated for the treatment of opioid dependence and are preferred for induction. buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9) ]. the data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but w

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rhodes pharmaceuticals l.p. - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 2 mg - hydromorphone hydrochloride oral solution and hydromorphone 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, which can occur at any dosage or duration [see warnings and precautions (5.2)] , reserve hydromorphone hydrochloride oral solution and hydromorphone 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. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. hydromorphone hydrochloride oral solution and hydromorphone 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 [see warnings and precautions (5.8)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] - hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite-containing medications (e.g., anaphylaxis) [see warnings and precautions (5.16), adverse reactions (6.1)] risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)]. there are no available data with hydromorphone hydrochloride in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (hdd), respectively. in published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the hdd and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the hdd to pregnant mice. no malformations were noted at 4 or 40.5 times the hdd in pregnant rats or rabbits, respectively [see data]. based on animal data, advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). there was no evidence of malformations or embryotoxicity reported. pregnant rabbits were treated with hydromorphone hydrochloride from gestation day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). there was no evidence of malformations or embryotoxicity reported. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on gestation day 8 to pregnant hamsters (6.4 to 87.2 times the hdd of 24 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. no neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day). in a published study, cf-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (gestation days 7 to 10). soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. the findings cannot be clearly attributed to maternal toxicity. increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from gestation day 7 to lactation day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested. risk summary low levels of opioid analgesics have been detected in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets and any potential adverse effects on the breastfed infant from hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor infants exposed to hydromorphone hydrochloride through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of hydromorphone hydrochloride in pediatric patients have not been established. elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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 hydromorphone hydrochloride slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)] . hydromorphone 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. the pharmacokinetics of hydromorphone is affected by hepatic impairment. due to increased exposure of hydromorphone, patients with hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and regularly evaluated during dose titration. the pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. a further increase in cmax and auc of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see clinical pharmacology (12.3)]. the pharmacokinetics of hydromorphone is affected by renal impairment. in addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life. start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. patients with renal impairment should be regularly evaluated during dose titration [see clinical pharmacology (12.3)]. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a schedule ii controlled substance. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.2)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, 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 hydromorphone 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 hydromorphone hydrochloride 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 hydromorphone hydrochloride abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use hydromorphone 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. hydromorphone 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 hydromorphone hydrochloride abuse of hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of hydromorphone hydrochloride with alcohol and/or other cns depressants. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of hydromorphone hydrochloride oral solution and hydromorphone 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 hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydromorphone hydrochloride oral solution and hydromorphone 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 (2.7), 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)].

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

teva pharmaceuticals usa, inc. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - buprenorphine 5 ug in 1 h - buprenorphine transdermal system 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 risk of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve buprenorphine transdermal system 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. - buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic buprenorphine transdermal system is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the

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rhodes pharmaceuticals l.p. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz) - buprenorphine 2 mg - buprenorphine sublingual tablets are indicated for the treatment of opioid dependence and are preferred for induction. buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)]. risk summary the data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see data]. reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. pre- and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. no clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. however, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. in a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risks of major birth defects and miscarriage for the indicated population are 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. dose adjustment during pregnancy and the postpartum period dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. withdrawal signs and symptoms should be monitored closely 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 buprenorphine sublingual 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 buprenorphine maintenance therapy may require additional analgesia during labor. data human data studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. interpretation of data is complicated further by the lack of information on untreated opioid-dependent pregnant women, who would be the most appropriate group for comparison. rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. however, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. 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 buprenorphine-treated and methadone-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 buprenorphine and methadone groups, the study findings are difficult to interpret. animal data the exposure margins listed below are based on body surface area comparisons (mg/m2 ) to the human sublingual dose of 16 mg buprenorphine via buprenorphine sublingual tablets. no definitive drug-related teratogenic effects were observed in rats and rabbits at im doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the human sublingual dose of 16 mg). maternal toxicity resulting in mortality was noted in these studies in both rats and rabbits. acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. maternal toxicity was seen in the high-dose group but not at the lower doses where the findings were observed. following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the human sublingual dose of 16 mg). in the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. following im administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. buprenorphine was not teratogenic in rats or rabbits after im or subcutaneous (sc) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the human sublingual dose of 16 mg), after iv doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the human sublingual dose of 16 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the human sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after sc administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the human sublingual dose of 16 mg), but were not observed at oral doses up to 160 mg/kg/day. increases in skeletal abnormalities in rabbits after im administration of 5 mg/kg/day (estimated exposure was approximately 6 times the human sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the human sublingual dose of 16 mg) were not statistically significant. in rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at iv doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the human sublingual dose of 16 mg). no maternal toxicity was noted at doses causing post-implantation loss in this study. dystocia was noted in pregnant rats treated intramuscularly with buprenorphine from gestation day 14 through lactation day 21 at 5 mg/kg/day (approximately 3 times the human sublingual dose of 16 mg). fertility, and pre- and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the human sublingual dose of 16 mg), after im doses of 0.5 mg/kg/day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after sc doses of 0.1 mg/kg/day and up (approximately 0.06 times the human sublingual dose of 16 mg). an apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the human sublingual dose of 16 mg). risk summary based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine were present in low levels in human milk and available data have not shown adverse reactions in breastfed infants. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for buprenorphine sublingual tablets and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. clinical considerations advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 to 24 mg/day, showing that the infants were exposed to less than 1% of the maternal daily dose. in a study of six lactating women who were taking a median sublingual buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equal to 0.2% and 0.12%, respectively, of the maternal weight-adjusted dose (relative dose/kg (%) of norbuprenorphine was calculated from the assumption that buprenorphine and norbuprenorphine are equipotent). data from a study of seven lactating women who were taking a median sublingual buprenorphine dose of 7 mg/day an average of 1.12 months after delivery indicated that the mean milk concentrations (cavg ) of buprenorphine and norbuprenorphine were 3.65 mcg/l and 1.94 mcg/l, respectively. based on the study data, and assuming milk consumption of 150 ml/kg/day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight-adjusted dose. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of buprenorphine sublingual tablets have not been established in pediatric patients. clinical studies of buprenorphine sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine and naloxone sublingual tablet did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine sublingual tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose. the effects of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a pharmacokinetic study. buprenorphine is extensively metabolized in the liver and buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. for patients with severe hepatic impairment, a dose adjustment is recommended, and patients with moderate or severe hepatic impairment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine [see dosage and administration (2.7), warnings and precautions (5.12), clinical pharmacology (12.3)] . no differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following iv administration of 0.3 mg buprenorphine. buprenorphine sublingual tablets contain buprenorphine, a schedule iii controlled substance under the controlled substances act. buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. this should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. healthcare professionals should contact their state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. patients who continue to misuse, abuse, or divert, buprenorphine products or other opioids should be provided or referred for more intensive and structured treatment. abuse of buprenorphine poses a risk of overdose and death. this risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. the healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs. buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. the withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see warnings and precautions (5.7) ]. neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.5)] . this "instructions for use" contains information on how to correctly take buprenorphine sublingual tablets. important information you need to know before taking buprenorphine sublingual tablets: - your healthcare provider should show you how to take buprenorphine sublingual tablets the right way. preparing to take buprenorphine sublingual tablets: - put the tablets under your tongue. let them dissolve completely. - while buprenorphine sublingual tablets are dissolving, do not chew or swallow the tablet because the medicine will not work as well. - talking while the tablet is dissolving can affect how well the medicine in buprenorphine sublingual tablets is absorbed. - after buprenorphine sublingual tablet is completely dissolved, rinse your mouth with water and swallow. wait for at least one hour before brushing teeth. - if you miss a dose of buprenorphine sublingual tablets, take your medicine when you remember. if it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. do not take 2 doses at the same time unless your healthcare provider tells you to. if you are not sure about your dosing, call your healthcare provider. - do not stop taking buprenorphine sublingual tablets suddenly. you could become sick and have withdrawal symptoms because your body has become used to the medicine. physical dependence is not the same as drug addiction. your healthcare provider can tell you more about the differences between physical dependence and drug addiction. to have fewer withdrawal symptoms, ask your healthcare provider how to stop using buprenorphine sublingual tablets the right way. if you take too much buprenorphine sublingual tablets or overdose, call poison control or get emergency medical help right away. storing buprenorphine sublingual tablets: - store buprenorphine sublingual tablets at room temperature between 68°f to 77°f (20°c to 25°c). - keep buprenorphine sublingual tablets in a safe place, out of the sight and reach of children. disposing of buprenorphine sublingual tablets: - dispose of unused buprenorphine sublingual tablets as soon as you no longer need them. - dispose of expired, unwanted or unused buprenorphine sublingual tablets by promptly flushing down the toilet (if a drug take-back option is not readily available). visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. if you need help with disposal of buprenorphine sublingual tablets, call rhodes pharmaceuticals at 1-888-827-0616. this "instructions for use" has been approved by the u.s. food and drug administration . revised 4/2023

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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)].

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remedyrepack inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz) - buprenorphine 2 mg - buprenorphine sublingual tablets are indicated for the treatment of opioid dependence and are preferred for induction. buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9) ]. the data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but

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

hikma pharmaceuticals usa inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz) - buprenorphine 2 mg - buprenorphine sublingual tablets are indicated for the treatment of opioid dependence and are preferred for induction. buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)] . risk summary: the data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data]. observational studies have reported on congenital malformations among buprenorphine-exposed pregn