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

alvogen inc. - ketorolac tromethamine (unii: 4eve5946bq) (ketorolac - unii:yzi5105v0l) - ketorolac tromethamine 15 mg in 1 ml - carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). ketorolac tromethamine is indicated for the short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. therapy should always be initiated with iv or im dosing of ketorolac tromethamine, and oral ketorolac tromethamine is to be used only as continuation treatment, if necessary. the total combined duration of use of ketorolac tromethamine injection, and oral ketorolac tromethamine is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see warnings, precautions, dosage and administration , and adverse reactions ). patients should be switched to alternative analgesics a

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

alvogen inc. - methylphenidate hydrochloride (unii: 4b3sc438hi) (methylphenidate - unii:207zz9qz49) - methylphenidate hydrochloride 20 mg - attention deficit disorders (previously known as minimal brain dysfunction in children). other terms being used to describe the behavioral syndrome below include: hyperkinetic child syndrome, minimal brain damage, minimal cerebral dysfunction, minor cerebral dysfunction. methylphenidate hydrochloride extended-release tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. the diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. nonlocalizing (soft) neurological signs, learning disability, and abnormal eeg may or may not be present, and a diagnosis of central nervous system dysfunction may or m

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

alvogen inc. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - 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 ¼ of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily sc buprenorphine at doses of 0.05 mg/kg, 0.5 mg/kg, or 5 mg/kg from gestation day 6 to lactation day 21 (weaning). administration of buprenorphine transdermal system or sc buprenorphine at 0.5 mg/kg 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 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)]. instructions for use buprenorphine (bue” pre nor’ feen) transdermal system ciii 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. figure j 1. peel back the disposal unit liner to show the sticky surface (see figure k ). figure k 2. place the sticky side of the used or unused patch to the indicated area on the disposal unit (see figure l ). 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. figure m 4. the closed disposal unit, with the patch sealed inside may be thrown away in the trash (see figure n ). 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 ). 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. made in usa distributed by: alvogen, inc. pine brook, nj 07058 usa revised: 04/2021 ifu406-00 bioclusive is a trademark of systagenix wound management (us), inc. tegaderm is a trademark of 3m.

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

alvogen inc. - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate 400 mg - felbamate tablets, usp are not indicated as a first line antiepileptic treatment (see warnings). felbamate tablets are recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgment, felbamate tablets can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate tablets are contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a history of any blood dyscras

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

alvogen inc. - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate tablets, usp are not indicated as a first line antiepileptic treatment (see warnings). felbamate tablets are recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgment, felbamate tablets can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate tablets are contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a history of any blood dyscras

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

alvogen, inc. - teriparatide (unii: 10t9csu89i) (teriparatide - unii:10t9csu89i) - teriparatide injection is indicated: - for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. in postmenopausal women with osteoporosis, teriparatide injection reduces the risk of vertebral and nonvertebral fractures. - to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. - for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. teriparatide injection is contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients. hypersensitivity reactio

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

alvogen inc. - lisdexamfetamine dimesylate (unii: sjt761gegs) (lisdexamfetamine - unii:h645gul8kj) - lisdexamfetamine dimesylate capsules are  indicated for the treatment of: - attention deficit hyperactivity disorder (adhd) in adults and pediatric patients 6 years and older [see clinical studies (14.1)] . - moderate to severe binge eating disorder (bed) in adults [see clinical studies (14.2)] . limitations of use: - pediatric patients with adhd younger than 6 years of age experienced more long-term weight loss than patients 6 years and older [see use in specific populations (8.4)] . - lisdexamfetamine dimesylate capsules are not indicated or recommended for weight loss. use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. the safety and effectiveness of lisdexamfetamine dimesylate capsules for the treatment of obesity have not been established [see warnings and precautions (5.2)] . lisdexamfetamine dimesylate capsules are contraindicated in patients with: - known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate capsules. anaphylactic reactions, stevens-johnson syndrome, angioedema, and urticaria have been observed in postmarketing reports [see adverse reactions (6.2)] . - patients taking monoamine oxidase inhibitors (maois), or within 14 days of stopping maois (including maois such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see warnings and precautions (5.7) and drug interactions (7.1)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/adhdmedications/. risk summary the limited available data from published literature and postmarketing reports on use of lisdexamfetamine dimesylate in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines [see clinical considerations] . in animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis. pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate. however, amphetamine (d- to l- ratio of 3:1) administration to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. in addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine [see data] . 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 amphetamines, such as lisdexamfetamine dimesylate, cause vasoconstriction and thereby may decrease placental perfusion. in addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight. monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. data animal data lisdexamfetamine dimesylate had no apparent effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 40 mg/kg/day and 120 mg/kg/day, respectively. these doses are approximately 5.5 and 33 times, respectively, the maximum recommended human dose (mrhd) of 70 mg/day given to adults, on a mg/m2 body surface area basis. a study was conducted with amphetamine (d- to l- enantiomer ratio of 3:1) in which pregnant rats received daily oral doses of 2 mg/kg, 6 mg/kg, and 10 mg/kg from gestation day 6 to lactation day 20. all doses caused hyperactivity and decreased weight gain in the dams. a decrease in pup survival was seen at all doses. a decrease in pup body weight was seen at 6 mg/kg and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. when pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg. a number of studies from the literature in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d, l-) at doses similar to those used clinically can result in long-term neurochemical and behavioral alterations. reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. risk summary lisdexamfetamine is a pro-drug of dextroamphetamine. based on limited case reports in published literature, amphetamine (d-or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. there are no reports of adverse effects on the breastfed infant. long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. it is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. because of the potential for serious adverse reactions in nursing infants, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breastfeeding is not recommended during treatment with lisdexamfetamine dimesylate capsules. adhd safety and effectiveness of lisdexamfetamine dimesylate capsules have been established in pediatric patients with adhd ages 6 to 17 years [see dosage and administration (2.3), adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.1)] . safety and effectiveness of lisdexamfetamine dimesylate capsules have not been established in pediatric patients below the age of 6 years. safety and efficacy of lisdexamfetamine dimesylate capsules were evaluated in a double-blind, randomized, parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages 4 to 5 years with adhd, followed by a 1-year open-label extension study. in these studies, patients experienced elevated rates of adverse reactions, including weight loss, decreased bmi, decreased appetite, insomnia, infections (upper respiratory and nasopharyngitis), irritability, and affect lability. with the same lisdexamfetamine dimesylate capsules dose, mean steady state exposure of dextroamphetamine was approximately 44% higher in pediatric patients ages 4 to 5 years compared to the pediatric patients ages 6 to 11 years. bed safety and effectiveness of lisdexamfetamine dimesylate capsules have not been established in pediatric patients with bed less than 18 years of age. growth suppression growth should be monitored during treatment with stimulants, including lisdexamfetamine dimesylate capsules, and pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions (5.5) and adverse reactions (6.1)] . juvenile animal data studies conducted in juvenile rats and dogs at clinically relevant doses showed growth suppression that partially or fully reversed in dogs and female rats but not in male rats after a four-week drug-free recovery period. a study was conducted in which juvenile rats received oral doses of 4 mg/kg/day, 10 mg/kg/day, or 40 mg/kg/day of lisdexamfetamine dimesylate from day 7 to day 63 of age. these doses are approximately 0.3, 0.7, and 3 times the maximum recommended human daily dose of 70 mg on a mg/m2 basis for a child. dose-related decreases in food consumption, bodyweight gain, and crown-rump length were seen; after a four-week drug-free recovery period, bodyweights and crown-rump lengths had significantly recovered in females but were still substantially reduced in males. time to vaginal opening was delayed in females at the highest dose, but there were no drug effects on fertility when the animals were mated beginning on day 85 of age. in a study in which juvenile dogs received lisdexamfetamine dimesylate for 6 months beginning at 10 weeks of age, decreased bodyweight gain was seen at all doses tested (2 mg/kg/day, 5 mg/kg/day, and 12 mg/kg/day, which are approximately 0.5, 1, and 3 times the maximum recommended human daily dose on a mg/m2 basis for a child). this effect partially or fully reversed during a four-week drug-free recovery period. clinical studies of lisdexamfetamine dimesylate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience and pharmacokinetic data [see clinical pharmacology (12.3)] have not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should start 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. due to reduced clearance in patients with severe renal impairment (gfr 15 to < 30 ml/min/1.73 m2 ), the maximum dose should not exceed 50 mg/day. the maximum recommended dose in esrd (gfr < 15 ml/min/1.73 m2 ) patients is 30 mg/day [see clinical pharmacology (12.3)] . lisdexamfetamine and d-amphetamine are not dialyzable. lisdexamfetamine dimesylate capsule contains lisdexamfetamine, a prodrug of amphetamine, a schedule ii controlled substance. lisdexamfetamine dimesylate capsules have a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see warnings and precautions (5.1)] . lisdexamfetamine dimesylate capsules can be diverted for non-medical use into illicit channels or distribution.  abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the 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 lisdexamfetamine, a prodrug of amphetamine, may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with cns stimulants abuse and/or misuse. misuse and abuse of cns stimulants, including lisdexamfetamine dimesylate capsules, can result in overdose and death [see overdosage (10)] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.  studies of lisdexamfetamine dimesylate in drug abusers a randomized, double-blind, placebo-control, cross-over, abuse liability study in 38 patients with a history of drug abuse was conducted with single-doses of 50 mg, 100 mg, or 150 mg of lisdexamfetamine dimesylate, 40 mg of immediate-release d-amphetamine sulphate (a controlled ii substance), and 200 mg of diethylpropion hydrochloride (a controlled iv substance). lisdexamfetamine dimesylate 100 mg produced significantly less “drug liking effects” as measured by the drug rating questionnaire-subject score, compared to d-amphetamine 40 mg; and 150 mg of lisdexamfetamine dimesylate demonstrated similar “drug-liking effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion. intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring “drug liking”, “euphoria”, “amphetamine effects”, and “benzedrine effects” that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous d-amphetamine. physical dependence lisdexamfetamine dimesylate capsules may produce physical dependence. physical dependence is a state that develops as a result of 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 signs and symptoms after abrupt discontinuation or dose reduction followingprolonged use of cns stimulants including lisdexamfetamine dimesylate capsules include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance lisdexamfetamine dimesylate capsules may produce tolerance. 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).

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

alvogen, inc. - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions (5.1)] , reserve oxycodone hydrochloride tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): • have not been tolerated or are not expected to be tolerated, • have not provided adequate analgesia or are not expected to provide adequate analgesia. oxycodone hydrochloride tablets 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. oxycodone hydrochloride tablets are contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)]. - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment or hypercarbia [see warnings and precautions (5.8)]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] . - known hypersensitivity (e.g., anaphylaxis) to oxycodone [see adverse reactions (6.2)] . 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 oxycodone hydrochloride tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. animal reproduction studies with oral administrations of oxycodone hydrochloride in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. in several published studies, treatment of pregnant rats with oxycodone at clinically relevant doses and below, resulted in neurobehavioral effects in offspring [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents irritability, hyperactivity, and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid use, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. oxycodone hydrochloride tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including oxycodone 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 in embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone hydrochloride administered during the period of organogenesis up to 16 mg/kg/day and up to 25 mg/kg/day, respectively. these studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. the highest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day, respectively, on a mg/m2 basis. in published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior (2 mg/kg/day iv from gestation day 8 to 21 and postnatal day 1, 3, and 5; 0.3 times an adult human dose of 60 mg/day, on a mg/m2 basis) and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m2 basis). risk summary oxycodone is present in breast milk. published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. the lactation studies did not assess breastfed infants for potential adverse reactions. lactation studies have not been conducted with oxycodone hydrochloride tablets, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxycodone hydrochloride tablets and any potential adverse effects on the breastfed infant from oxycodone hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor infants exposed to oxycodone hydrochloride through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2)] . the safety and efficacy of oxycodone hydrochloride tablets in pediatric patients have not been evaluated. of the total number of subjects in clinical studies of oxycodone hydrochloride tablets, 20.8% (112/538) were 65 and over, while 7.2% (39/538) were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of oxycodone hydrochloride tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.2)] . oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. because oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. initiate therapy in these patients with a lower than usual dosage of oxycodone hydrochloride tablets and titrate carefully. regularly evaluate for adverse events such as respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)] . because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with renal impairment. initiate therapy with a lower than usual dosage of oxycodone hydrochloride tablets and titrate carefully. regularly evaluate for adverse events such as respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)] . oxycodone hydrochloride tablets contain oxycodone, a schedule ii controlled substance. oxycodone hydrochloride tablets contain oxycodone, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of oxycodone hydrochloride tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of oxycodone hydrochloride tablets 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 oxycodone hydrochloride tablets abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use oxycodone hydrochloride tablets in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. oxycodone hydrochloride tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of oxycodone hydrochloride tablets abuse of oxycodone hydrochloride tablets pose a risk of overdose and death. the risk is increased with concurrent use of oxycodone hydrochloride tablets with alcohol and/or other cns depressants. oxycodone 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 oxycodone hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of oxycodone 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 oxycodone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone 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 (2.4), and warnings and precautions (5.14)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] .

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

alvogen inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride dihydrate (unii: 5q187997ee) (naloxone - unii:36b82amq7n) - buprenorphine and naloxone sublingual film is indicated for treatment of opioid dependence. buprenorphine and naloxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support. buprenorphine and naloxone sublingual film is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9) ] . the data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual film, 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] . the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug-associated risk. 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‐times and 0.3‐times, respectively, the human sublingual dose of 16 mg per day of buprenorphine. pre‐and postnatal 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 per 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 per 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 per 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 risk 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. untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. dosage 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. neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual film. 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)] . opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data on malformations 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 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. 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 and naloxone sublingual tablets. effects on embryo‐fetal development were studied in sprague‐dawley rats and russian white rabbits following oral (1:1) and intramuscular (im) (3:2) administration of mixtures of buprenorphine and naloxone during the period of organogenesis. following oral administration to rats, no teratogenic effects were observed at buprenorphine doses up to 250 mg/kg per day (estimated exposure approximately 150 times the human sublingual dose of 16 mg) in the presence of maternal toxicity (mortality). following oral administration to rabbits, no teratogenic effects were observed at buprenorphine doses up to 40 mg/kg per day (estimated exposure approximately 50 times the human sublingual dose of 16 mg) in the absence of clear maternal toxicity. no definitive drug‐related teratogenic effects were observed in rats and rabbits at intramuscular doses up to 30 mg/kg per 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 per 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 per day. following intramuscular 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 per day. buprenorphine was not teratogenic in rats or rabbits after intramuscular or subcutaneous doses up to 5 mg/kg per day (estimated exposure was approximately 3 times and 6 times, respectively, the human sublingual dose of 16 mg), after intravenous doses up to 0.8 mg/kg per 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 per day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg per day in rabbits (estimated exposure was approximately 30 times the human daily sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco‐lumbar ribs) were noted in rats after subcutaneous administration of 1 mg/kg per 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 per day. increases in skeletal abnormalities in rabbits after intramuscular administration of 5 mg/kg per day (estimated exposure was approximately 6 times the human daily sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg per 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 per day or greater and post‐implantation losses that were statistically significant at intravenous doses of 0.2 mg/kg per day or greater (estimated exposure approximately 0.3 times the human daily 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 per day (approximately 3 times the human sublingual dose of 16 mg). fertility, pre‐, and post‐natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg per day and up (approximately 0.5 times the human daily sublingual dose of 16 mg), after intramuscular doses of 0.5 mg/kg per day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after subcutaneous doses of 0.1 mg/kg per 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 per day (approximately 50 times the human sublingual dose of 16 mg). 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 infant urine. available data have not shown adverse reactions in breastfed infants. there are no data on the combination product buprenorphine and naloxone in breastfeeding, however oral absorption of naloxone is limited. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for buprenorphine and naloxone sublingual film and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 mg per day to 24 mg per 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 per day 5 days to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg per day of buprenorphine and 0.33 mcg/kg per 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 per 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 per day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg per day of buprenorphine and 0.29 mcg/kg per day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight‐adjusted dose. 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 and naloxone sublingual film have not been established in pediatric patients. this product is not appropriate for the treatment of neonatal abstinence syndrome in neonates, because it contains naloxone, an opioid antagonist. clinical studies of buprenorphine and naloxone sublingual film, buprenorphine and naloxone sublingual tablets, or buprenorphine sublingual tablets 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 and naloxone sublingual film 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 effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone has been evaluated in a pharmacokinetic study. both drugs are extensively metabolized in the liver. while no clinically significant changes have been observed in subjects with mild hepatic impairment; the plasma levels have been shown to be higher and half-life values have been shown to be longer for both buprenorphine and naloxone in subjects with moderate and severe hepatic impairment. the magnitude of the effects on naloxone are greater than that on buprenorphine in both moderately and severely impaired subjects. the difference in magnitude of the effects on naloxone and buprenorphine are greater in subjects with severe hepatic impairment than in subjects with moderate hepatic impairment, and therefore the clinical impact of these effects is likely to be greater in patients with severe hepatic impairment than in patients with moderate hepatic impairment. buprenorphine and naloxone products should be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment [see 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 intravenous administration of 0.3 mg buprenorphine. the effects of renal failure on naloxone pharmacokinetics are unknown. buprenorphine and naloxone sublingual film contains 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 with 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)] .

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

alvogen inc. - naproxen sodium (unii: 9tn87s3a3c) (naproxen - unii:57y76r9atq) - naproxen 375 mg - naproxen sodium controlled-release tablets are indicated for the treatment of: - rheumatoid arthritis (ra) - osteoarthritis (oa) - ankylosing spondylitis (as) - tendinitis, bursitis - acute gout - primary dysmenorrhea (pd) - the relief of mild to moderate pain  [see warnings and precautions (5) ]. naproxen sodium controlled-release tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see warnings and precautions (5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1) ] risk summary use of nsaids, including naproxen sodium controlled-release tablets, can cause premature closure o