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amneal pharmaceuticals ny llc - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus oral solution is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus oral solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus oral solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3)  and clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdr

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amneal pharmaceuticals ny llc - pregabalin (unii: 55jg375s6m) (pregabalin - unii:55jg375s6m) - pregabalin capsules are indicated for: - management of neuropathic pain associated with diabetic peripheral neuropathy - management of postherpetic neuralgia - adjunctive therapy for the treatment of partial-onset seizures in patients 17 years of age and older -   management of fibromyalgia - management of neuropathic pain associated with spinal cord injury pediatric use information is approved for pfizer’s lyrica (pregabalin) capsules. however, due to pfizer’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. pregabalin capsules are contraindicated in patients with known hypersensitivity to pregabalin or any of its components. angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin during pregnancy. to provide information regarding the effects of in utero exposure to pregabalin, physicians are advised to recommend that pregnant patients taking pregabalin enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. risk summary there are no adequate and well-controlled studies with pregabalin in pregnant women. however, in animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (auc) greater than or equal to 16 times human exposure at the maximum recommended dose (mrd) of 600 mg/day [see data] . in an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. the no-effect dose for developmental toxicity was approximately twice the human exposure at mrd. the background risk of major birth defects and miscarriage for the indicated populations are unknown. however, the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. advise pregnant women of the potential risk to a fetus. data animal data when pregnant rats were given pregabalin (500, 1,250, or 2,500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1,250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. fetal body weights were decreased at the highest dose. the low dose in this study was associated with a plasma exposure (auc) approximately 17 times human exposure at the mrd of 600 mg/day. a no-effect dose for rat embryo-fetal developmental toxicity was not established. when pregnant rabbits were given pregabalin (250, 500, or 1,250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. the no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the mrd. in a study in which female rats were dosed with pregabalin (50, 100, 250, 1,250, or 2,500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. the effect on offspring survival was pronounced at doses greater than or equal to 1,250 mg/kg, with 100% mortality in high-dose litters. when offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1,250 mg/kg. the no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the mrd. in the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (auc(0 to 24) of 123 mcg•hr/ml) at the mrd. risk summary small amounts of pregabalin have been detected in the milk of lactating women. a pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. the estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 ml/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose [see data] . the study did not evaluate the effects of pregabalin on milk production or the effects of pregabalin on the breastfed infant. based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant [see nonclinical toxicology (13.1)] . available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin [see warnings and precautions (5.9)] . because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with pregabalin. data a pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. pregabalin 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of four doses. pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. the estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 ml/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. the study did not evaluate the effects of pregabalin on milk production. infants did not receive breast milk obtained during the dosing period, therefore, the effects of pregabalin on the breast fed infant were not evaluated. infertility male effects on spermatogenesis in a randomized, double-blind, placebo-controlled non-inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (one complete sperm cycle) followed by a 13-week washout period (off-drug). a total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (pp) population. these subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at week 26 (the primary endpoint). the difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. there were no adverse effects of pregabalin on sperm morphology, sperm motility, serum fsh or serum testosterone levels as compared to placebo. in subjects in the pp population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off-drug. in one subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off-drug. the clinical relevance of these data is unknown. in the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see nonclinical toxicology (13.1)]. neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and neuropathic pain associated with spinal cord injury safety and effectiveness in pediatric patients have not been established. fibromyalgia safety and effectiveness in pediatric patients have not been established. a 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at pregabalin total daily doses of 75 to 450 mg per day. the primary efficacy endpoint of change from baseline to week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. the most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. the overall safety profile in adolescents was similar to that observed in adults with fibromyalgia. adjunctive therapy for partial-onset seizures safety and effectiveness in pediatric patients below the age of 1 month have not been established. juvenile animal data in studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (postnatal day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. the neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. the low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (auc) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. a no-effect dose was not established. information describing a clinical study in which efficacy was not demonstrated in patients is approved for pfizer inc.’s lyrica® (pregabalin) products. additional pediatric use information is approved for pfizer’s lyrica (pregabalin) capsules. however, due to pfizer’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. in controlled clinical studies of pregabalin in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older. in controlled clinical studies of pregabalin in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older. in controlled clinical studies of pregabalin in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older. no overall differences in safety and efficacy were observed between these patients and younger patients. in controlled clinical studies of pregabalin in fibromyalgia, 106 patients were 65 years of age or older. although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy. pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function. because pregabalin is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see dosage and administration (2.7)] . pregabalin is eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment [see dosage and administration (2.7) and clinical pharmacology (12.3)]. the use of pregabalin in pediatric patients with compromised renal function has not been studied. pregabalin is a schedule v controlled substance. pregabalin is not known to be active at receptor sites associated with drugs of abuse. as with any cns active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior). in a study of recreational users (n=15) of sedative/hypnotic drugs, including alcohol, pregabalin (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose). in controlled clinical studies in over 5,500 patients, 4% of pregabalin-treated patients and 1 % of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1% to 12%. in clinical studies, following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see warnings and precautions (5.6)] , consistent with physical dependence. in the postmarketing experience, in addition to these reported symptoms there have also been reported cases of anxiety and hyperhidrosis.

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amneal pharmaceuticals ny llc - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - arthritis pain reliever  for the temporary relief of arthritis pain only in the following areas  head, wrist, elbow (upper body areas)  foot, ankle, knee (lower body areas)  this product may take up to 7 days to work for arthritis pain; it is not for immediate relief. if no pain relief in 7 days, stop use.

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

amneal pharmaceuticals ny llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hcl extended-release tablets are 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 in: - adults; and - opioid-tolerant pediatric patients 11 years of age and older who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve oxycodone hcl extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - oxycodone hcl extended-release tablets are not indicated as an as-needed (prn) analgesic. oxycodone hcl extended-release 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 (5.7)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] - hypersensitivity (e.g., anaphylaxis) to oxycodone [see  adverse reactions (6.2)] risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] .  there are no available data with oxycodone hcl extended-release tablets in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.  in animal reproduction studies, there was no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the period of organogenesis, at doses 1.3 to 40 times the adult human dose of 60 mg/day, respectively.  in a pre- and postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup body weight during lactation and the early post-weaning period at the dose equivalent to an adult dose of 60 mg/day.  in several published studies, treatment of pregnant rats with oxycodone hydrochloride at clinically relevant doses and below resulted in neurobehavioral effects in offspring [see data].  based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown.  all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.   clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics 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.  oxycodone hcl extended-release tablets is not recommended for use in women immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including oxycodone hcl extended-release 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 dilatation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data pregnant rats were treated with 0.5, 2, 4, and 8 mg/kg oxycodone hydrochloride (0.08, 0.3, 0.7, and 1.3 times the human daily dose of 60 mg/day, respectively based on a mg/m2 basis) during the period of organogenesis.  oxycodone did not cause adverse effects to the fetus at exposures up to 1.3 times the human dose of 60 mg/day.  the high dose produced maternal toxicity characterized by excessive gnawing on forelimbs and decreased body weight gain. pregnant rabbits were treated with 1, 5, 25, and 125 mg/kg oxycodone hydrochloride (0.3, 2, 8, and 40 times the human daily dose of 60 mg/day, respectively, based on a mg/m2 basis) during the period of organogenesis.  oxycodone did not cause adverse effects to the fetus at exposures up to 40 times the human dose of 60 mg/day.  the 25 mg/kg and 125 mg/kg doses high doses produced maternal toxicity characterized by decreased food consumption and body weight gain. pregnant rats were treated with 0.5, 2, and 6 mg/kg oxycodone hydrochloride (0.08, 0.32, and 1 times the human daily dose of 60 mg/kg, respective, based on a mg/m2 basis, during the period of organogenesis through lactation.  decreased body weight was found during lactation and the early post-weaning phase in pups nursed by mothers given the highest dose used (6 mg/kg/day, equivalent to an adult human dose of 60 mg/day, on a mg/m2 basis).  however, body weight of these pups recovered.  in published studies, offspring of pregnant rats administered oxycodone hydrochloride during gestation have been reported to exhibit neurobehavioral effects including altered stress responses and increased anxiety-like behavior (2 mg/kg/day iv from gestation day 8 to 21 and postnatal day 1, 3, and 5; 0.3 times an adult human oral dose of 60 mg/day on a mg/m2 basis), and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human oral dose of 60 mg/day on a mg/m2 basis). oxycodone is present in breast milk. published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. the lactation studies did not assess breastfed infants for potential adverse reactions. lactation studies have not been conducted with extended–release oxycodone, including oxycodone hcl extended-release 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.  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 oxycodone hcl extended-release tablets. clinical considerations infants exposed to oxycodone hcl extended-release tablets through breast milk should be monitored 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 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)] . the safety and efficacy of oxycodone hcl extended-release tablets have been established in pediatric patients ages 11 to 16 years.  use of oxycodone hcl extended-release tablets are supported by evidence from adequate and well-controlled trials with oxycodone hcl extended-release tablets in adults as well as an open-label study in pediatric patients ages 6 to 16 years. however, there were insufficient numbers of patients less than 11 years of age enrolled in this study to establish the safety of the product in this age group.  the safety of oxycodone hcl extended-release tablets in pediatric patients was evaluated in 155 patients previously receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent on the two days immediately preceding dosing with oxycodone hcl extended-release tablets.  patients were started on a total daily dose ranging between 20 mg and 100 mg depending on prior opioid dose. the most frequent adverse events observed in pediatric patients were vomiting, nausea, headache, pyrexia, and constipation [see dosage and administration (2.5), adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)] . in controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced.  compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see clinical pharmacology (12.3)] .  of the total number of subjects (445) in clinical studies of oxycodone hydrochloride controlled-release tablets, 148 (33.3%) were age 65 and older (including those age 75 and older) while 40 (9.0%) were age 75 and older.  in clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received oxycodone hydrochloride controlled-release tablets.  thus, the usual doses and dosing intervals may be appropriate for elderly patients. however, a dosage reduction in debilitated, non-opioid-tolerant patients is recommended [see dosage and administration (2.8)] .  respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who are not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of oxycodone hcl extended-release tablets slowly in these patients and monitor closely for signs of central nervous system and respiratory depression. [see warnings and precautions (5.7)] . 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 monitor renal function. a study of oxycodone hcl extended-release tablets in patients with hepatic impairment demonstrated greater plasma concentrations than those seen at equivalent doses in persons with normal hepatic function [see clinical pharmacology (12.3)] .  therefore, a dosage reduction is recommended for these patients [see dosage and administration (2..9)]. monitor closely for signs of respiratory depression, sedation, and hypotension.   in patients with renal impairment, as evidenced by decreased creatinine clearance (<60 ml/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function [see clinical pharmacology (12.3)] .  follow a conservative approach to dose initiation and adjust according to the clinical situation. in pharmacokinetic studies with oxycodone hcl extended-release tablets, opioid-naïve females demonstrate up to 25% higher average plasma concentrations and greater frequency of typical opioid adverse events than males, even after adjustment for body weight.  the clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages, and there was no male/female difference detected for efficacy or adverse events in clinical trials. oxycodone hcl extended-release tablets contains oxycodone, a schedule ii controlled substance. oxycodone hcl extended-release tablets contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol.  oxycodone hcl extended-release tablets can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)]. the high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse. all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.  drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. "drug-seeking" behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction.  preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. oxycodone hcl extended release tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic 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 hcl extended-release tablets oxycodone hcl extended-release tablets are for oral use only. abuse of oxycodone hcl extended-release tablets poses a risk of overdose and death. the risk is increased with concurrent use of oxycodone hcl extended-release tablets with alcohol and other central nervous system depressants.  taking cut, broken, chewed, crushed, or dissolved oxycodone hcl extended-release tablets enhances drug release and increases the risk of overdose and death. with parenteral abuse, the inactive ingredients in oxycodone hcl extended-release tablets can be expected to result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, valvular heart injury, embolism, and death. cases of thrombotic microangiopathy (a condition characterized clinically by thrombocytopenia and microangiopathic hemolytic anemia) associated with parenteral abuse have been reported. parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and hiv. abuse deterrence studies oxycodone hcl extended-release tablets are formulated with inactive ingredients intended to make the tablet more difficult to manipulate for misuse and abuse. for the purposes of describing the results of studies of the abuse-deterrent characteristics of oxycodone hcl extended-release tablets resulting from a change in formulation, in this section, the original formulation of oxycodone hcl extended-release tablets, which is no longer marketed, will be referred to as “original oxycodone hcl extended-release tablets” and the reformulated, currently marketed product will be referred to as “oxycodone hcl extended-release tablets ".  in vitro testing in vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation.  results support that, relative to original oxycodone hcl extended-release tablets, there is an increase in the ability of oxycodone hcl extended-release tablets to resist crushing, breaking, and dissolution using a variety of tools and solvents.  the results of these studies also support this finding for oxycodone hcl extended-release tablets relative to an immediate-release oxycodone. when subjected to an aqueous environment, oxycodone hcl extended-release tablets gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a needle.  clinical studies in a randomized, double-blind, placebo-controlled 5-period crossover pharmacodynamic study, 30 recreational opioid users with a history of intranasal drug abuse received intranasally administered active and placebo drug treatments.  the five treatment arms were finely crushed oxycodone hcl extended-release tablets 30 mg tablets, coarsely crushed oxycodone hcl extended-release tablets 30 mg tablets, finely crushed original oxycodone hcl extended-release tablets 30 mg tablets, powdered oxycodone hcl 30 mg, and placebo. data for finely crushed oxycodone hcl extended-release tablets, finely crushed original oxycodone hcl extended-release tablets, and powdered oxycodone hcl are described below. drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking and 100 represents maximum liking.  response to whether the subject would take the study drug again was also measured on a bipolar scale of 0 to 100 where 50 represents a neutral response, 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”).  twenty-seven of the subjects completed the study.  incomplete dosing due to granules falling from the subjects’ nostrils occurred in 34% (n = 10) of subjects with finely crushed oxycodone hcl extended-release tablets, compared with 7% (n = 2) of subjects with finely crushed original oxycodone hcl extended-release tablets and no subjects with powdered oxycodone hcl. the intranasal administration of finely crushed oxycodone hcl extended-release tablets was associated with a numerically lower mean and median drug liking score and a lower mean and median score for take drug again, compared to finely crushed original oxycodone hcl extended-release tablets or powdered oxycodone hcl as summarized in table 5.   table 5:  summary of maximum drug liking (emax ) data following intranasal administration vas scale (100 mm)* oxycodone hcl extended-release tablets (finely crushed) original oxycodone hcl extended-release tablets (finely crushed) oxycodone hcl (powdered) drug liking mean (se) 80.4 (3.9) 94.0 (2.7) 89.3 (3.1) median (range) 88 (36-100) 100 (51-100) 100 (50-100) take drug again mean (se) 64.0 (7.1) 89.6 (3.9) 86.6 (4.4) median (range) 78 (0-100) 100 (20-100) 100 (0-100) * bipolar scales (0 = maximum negative response, 50 = neutral response, 100 = maximum positive response)   figure 1 demonstrates a comparison of drug liking for finely crushed oxycodone hcl extended-release tablets compared to powdered oxycodone hcl in subjects who received both treatments.  the y-axis represents the percent of subjects attaining a percent reduction in drug liking for oxycodone hcl extended-release tablets vs. oxycodone hcl powder greater than or equal to the value on the x-axis.  approximately 44% (n = 12) had no reduction in liking with oxycodone hcl extended-release tablets relative to oxycodone hcl.  approximately 56% (n = 15) of subjects had some reduction in drug liking with oxycodone hcl extended-release tablets relative to oxycodone hcl. thirty-three percent (n = 9) of subjects had a reduction of at least 30% in drug liking with oxycodone hcl extended-release tablets compared to oxycodone hcl, and approximately 22% (n = 6) of subjects had a reduction of at least 50% in drug liking with oxycodone hcl extended-release tablets compared to oxycodone hcl. figure 1: percent reduction profiles for emax of drug liking vas for oxycodone hcl extended-release tablets vs. oxycodone hcl, n=27 following intranasal administration the results of a similar analysis of drug liking for finely crushed oxycodone hcl extended-release tablets relative to finely crushed original oxycodone hcl extended-release tablets were comparable to the results of finely crushed oxycodone hcl extended-release tablets relative to powdered oxycodone hcl.  approximately 43% (n = 12) of subjects had no reduction in liking with oxycodone hcl extended-release tablets relative to original oxycodone hcl extended-release tablets.  approximately 57% (n = 16) of subjects had some reduction in drug liking, 36% (n = 10) of subjects had a reduction of at least 30% in drug liking, and approximately 29% (n = 8) of subjects had a reduction of at least 50% in drug liking with oxycodone hcl extended-release tablets compared to original oxycodone hcl extended-release tablets. summary the in vitro data demonstrate that oxycodone hcl extended-release tablets have physicochemical properties expected to make abuse via injection difficult. the data from the clinical study, along with support from the in vitro data, also indicate that oxycodone hcl extended-release tablets has physicochemical properties that are expected to reduce abuse via the intranasal route. however, abuse of oxycodone hcl extended-release tablets by these routes, as well as by the oral route, is still possible. additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of oxycodone hcl extended-release tablets on the abuse liability of the drug. accordingly, this section may be updated in the future as appropriate. oxycodone hcl extended-release tablets contains oxycodone, an opioid agonist and schedule ii controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. oxycodone hcl extended-release tablets can be abused and is subject to misuse, addiction, and criminal diversion [ see warnings and precautions (5.1) and drug abuse and dependence (9.1)].   both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors).  tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (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 opioid usage. do not abruptly discontinue oxycodone hcl extended-release tablets in a patient physically dependent on opioids. rapid tapering of oxycodone hcl extended-release 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 hcl extended-release tablets, gradually taper the dosage using a patient specific plan that considers the following: the dose of oxycodone hcl extended-release 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 a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.6), warnings and precautions (5.14)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] .  

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amneal pharmaceuticals ny llc - vigabatrin (unii: gr120krt6k) (vigabatrin - unii:gr120krt6k) - vigabatrin tablets are indicated as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see warnings and precautions (5.1)] . vigabatrin tablets are not indicated as a first line agent for complex partial seizures. vigabatrin is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see warnings and precautions (5.1)] . none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including vigabatrin, during pregnancy. encourage women who are taking vigabatrin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll-free number 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/. this must be done by the patient herself. risk summary there are no adequate data on the developmental risk associated with the use of vigabatrin in pregnant women. limited available data from case reports and cohort studies pertaining to vigabatrin use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, based on animal data, vigabatrin use in pregnant women may result in fetal harm. when administered to pregnant animals, vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral and neurohistopathological effects, at clinically relevant doses. in addition, developmental neurotoxicity was observed in rats treated with vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy (see data) . 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. animal data administration of vigabatrin (oral doses of 50 to 200 mg/kg/day) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryo-fetal death; these findings were observed in two separate studies. the no-effect dose for adverse effects on embryo-fetal development in rabbits (100 mg/kg/day) is approximately 1/2 the maximum recommended human dose (mrhd) of 3 g/day on a body surface area (mg/m2 ) basis. in rats, oral administration of vigabatrin (50, 100, or 150 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. the no-effect dose for adverse effects on embryo-fetal development in rats (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2  basis. oral administration of vigabatrin (50, 100, 150 mg/kg/day) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. a no-effect dose for developmental neurotoxicity in rats was not established; the low-effect dose (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2  basis. in a published study, vigabatrin (300 or 450 mg/kg) was administered by intraperitoneal injection to a mutant mouse strain on a single day during organogenesis (day 7, 8, 9, 10, 11, or 12). an increase in fetal malformations (including cleft palate) was observed at both doses. oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain vacuolation, decreased myelination, and retinal dysplasia) abnormalities in treated animals. the early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. the no-effect dose for developmental neurotoxicity in juvenile rats (5 mg/kg/day) was associated with plasma vigabatrin exposures (auc) less than 1/30 of those measured in pediatric patients receiving an oral dose of 50 mg/kg. risk summary vigabatrin is excreted in human milk. the effects of vigabatrin on the breastfed infant and on milk production are unknown. because of the potential for serious adverse reactions from vigabatrin in nursing infants, breastfeeding is not recommended. if exposing a breastfed infant to vigabatrin, observe for any potential adverse effects [see warnings and precautions (5.1, 5.3, 5.4, 5.8)] . the safety and effectiveness of vigabatrin as adjunctive treatment of refractory complex partial seizures in pediatric patients 2 to 16 years of age have been established and is supported by three double-blind, placebo-controlled studies in patients 3 to 16 years of age, adequate and well-controlled studies in adult patients, pharmacokinetic data from patients 2 years of age and older, and additional safety information in patients 2 years of age [see clinical pharmacology (12.3)  and clinical studies (14.1)] . the dosing recommendation in this population varies according to age group and is weight-based [see dosage and administration (2.2)] . adverse reactions in this pediatric population are similar to those observed in the adult population [see adverse reactions (6.1)] . the safety and effectiveness of vigabatrin as monotherapy for pediatric patients with infantile spasms (1 month to 2 years of age) have been established [see dosage and administration (2.3)  and clinical studies (14.2)] . safety and effectiveness as adjunctive treatment of refractory complex partial seizures in pediatric patients below the age of 2 and as monotherapy for the treatment of infantile spasms in pediatric patients below the age of 1 month have not been established. duration of therapy for infantile spasms was evaluated in a post hoc analysis of a canadian pediatric epilepsy network (cpen) study of developmental outcomes in infantile spasms patients. this analysis suggests that a total duration of 6 months of vigabatrin therapy is adequate for the treatment of infantile spasms. however, prescribers must use their clinical judgment as to the most appropriate duration of use [see clinical studies (14.2)] . abnormal mri signal changes and intramyelinic edema (ime) in infants and young children being treated with vigabatrin have been observed [see warnings and precautions (5.3, 5.4)] . juvenile animal toxicity data oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain gray matter vacuolation, decreased myelination, and retinal dysplasia) abnormalities. the no-effect dose for developmental neurotoxicity in juvenile rats (the lowest dose tested) was associated with plasma vigabatrin exposures (auc) substantially less than those measured in pediatric patients at recommended doses. in dogs, oral administration of vigabatrin (30 or 100 mg/kg/day) during selected periods of juvenile development (postnatal days 22 to 112) produced neurohistopathological abnormalities (brain gray matter vacuolation). neurobehavioral effects of vigabatrin were not assessed in the juvenile dog. a no-effect dose for neurohistopathology was not established in juvenile dogs; the lowest effect dose (30 mg/kg/day) was associated with plasma vigabatrin exposures lower than those measured in pediatric patients at recommended doses [see warnings and precautions (5.4)] . clinical studies of vigabatrin did not include sufficient numbers of patients aged 65 and over to determine whether they responded differently from younger patients. vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. oral administration of a single dose of 1.5 g of vigabatrin to elderly (≥65 years) patients with reduced creatinine clearance (<50 ml/min) was associated with moderate to severe sedation and confusion in 4 of 5 patients, lasting up to 5 days. the renal clearance of vigabatrin was 36% lower in healthy elderly subjects (≥65 years) than in young healthy males. adjustment of dose or frequency of administration should be considered. such patients may respond to a lower maintenance dose [see dosage and administration (2.4)  and clinical pharmacology (12.3)] . other reported clinical experience has not identified differences in responses between the elderly and younger patients. dose adjustment, including initiating treatment with a lower dose, is necessary in pediatric patients 2 years of age and older and adults with mild (creatinine clearance >50 to 80 ml/min), moderate (creatinine clearance >30 to 50 ml/min) and severe (creatinine clearance >10 to 30 ml/min) renal impairment [see dosage and administration (2.4)  and clinical pharmacology (12.3)] . vigabatrin is not a controlled substance. vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. it is not possible to predict the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior). following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation. however, as with all aeds, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see warnings and precautions (5.6)] .

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amneal pharmaceuticals ny llc - brexpiprazole (unii: 2j3ybm1k8c) (brexpiprazole - unii:2j3ybm1k8c) - brexpiprazole tablets are indicated for: - adjunctive treatment of major depressive disorder (mdd) in adults. - treatment of schizophrenia in adults. brexpiprazole tablets are contraindicated in patients with a known hypersensitivity to brexpiprazole or any of its components. reactions have included rash, facial swelling, urticaria, and anaphylaxis. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to brexpiprazole during pregnancy. for more information contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary adequate and well-controlled studies have not been conducted with brexpiprazole in pregnant women to inform drug-associated risks. however, neonates whose mothers are exposed to antipsychotic drugs, like brexpiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal sy

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amneal pharmaceuticals ny llc - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq) - naproxen oral suspension is indicated for: the relief of the signs and symptoms of: - rheumatoid arthritis - osteoarthritis - ankylosing spondylitis - polyarticular juvenile idiopathic arthritis - tendonitis - bursitis - acute gout the management of: - pain - primary dysmenorrhea naproxen oral suspension is 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 oral suspension, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leadin

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amneal pharmaceuticals ny llc - sodium oxybate (unii: 7g33012534) (4-hydroxybutanoic acid - unii:30iw36w5b2) - sodium oxybate oral solution is indicated for the treatment of cataplexy or excessive daytime sleepiness (eds) in patients 7 years of age and older with narcolepsy. sodium oxybate oral solution is contraindicated for use in: risk summary there are no adequate data on the developmental risk associated with the use of sodium oxybate in pregnant women. oral administration of sodium oxybate to pregnant rats (150, 350, or 1,000 mg/kg/day) or rabbits (300, 600, or 1,200 mg/kg/day) throughout organogenesis produced no clear evidence of developmental toxicity; however, oral administration to rats throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and growth, at a clinically relevant dose [see data] . in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. the background risk of major birth defects and miscarriage for the indicated population

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amneal pharmaceuticals ny llc - emtricitabine (unii: g70b4etf4s) (emtricitabine - unii:g70b4etf4s), tenofovir disoproxil fumarate (unii: ott9j7900i) (tenofovir anhydrous - unii:w4hfe001u5) - emtricitabine and tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 17 kg [see clinical studies (14)] . emtricitabine and tenofovir disoproxil fumarate tablets are indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection. individuals must have a negative hiv-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate tablets for hiv-1 prep [see dosage and administration (2.2), warnings and precautions (5.2)] .  emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep is contraindicated in individuals with unknown or positive hiv-1 status [see warnings and precautions (5.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil fumarate

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amneal pharmaceuticals ny llc - ticagrelor (unii: glh0314rvc) (ticagrelor - unii:glh0314rvc) - ticagrelor tablets are indicated to reduce the risk of cardiovascular death, myocardial infarction (mi), and stroke in patients with acute coronary syndrome (acs) or a history of mi. for at least the first 12 months following acs, it is superior to clopidogrel. ticagrelor tablets also reduce the risk of stent thrombosis in patients who have been stented for treatment of acs [see clinical studies (14.1)] . ticagrelor tablets are indicated to reduce the risk of a first mi or stroke in patients with coronary artery disease (cad) at high risk for such events [see clinical studies (14.2)]. while use is not limited to this setting, the efficacy of ticagrelor tablets were established in a population with type 2 diabetes mellitus (t2dm). ticagrelor tablets are contraindicated in patients with a history of intracranial hemorrhage (ich) because of a high risk of recurrent ich in this population [see clinical studies (14.1), (14.2)] . ticagrelor tablets are contraindicated in patients with active pathological bleeding