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amneal pharmaceuticals llc - alosetron hydrochloride (unii: 2f5r1a46yw) (alosetron - unii:13z9hth115) - alosetron 0.5 mg - alosetron tablets are indicated only for women with severe diarrhea-predominant irritable bowel syndrome (ibs) who have: - chronic ibs symptoms (generally lasting 6 months or longer), - had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and - not responded adequately to conventional therapy. diarrhea-predominant ibs is severe if it includes diarrhea and one or more of the following: - frequent and severe abdominal pain/discomfort, - frequent bowel urgency or fecal incontinence, - disability or restriction of daily activities due to ibs. because of infrequent but serious gastrointestinal adverse reactions associated withalosetron tablets, the indication is restricted to those patients for whom the benefit-to-risk balance is most favorable. clinical studies have not been performed to adequately confirm the benefits of alosetron tablets in men. alosetron hydrochloride should not be initiated in patients with constipation [see warnings and precautions (5.1)] . alosetron hydrochlori

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amneal pharmaceuticals of new york llc - alendronate sodium (unii: 2uy4m2u3ra) (alendronic acid - unii:x1j18r4w8p) - alendronic acid 5 mg - alendronate sodium tablets are indicated for the treatment of osteoporosis in postmenopausal women. in postmenopausal women, alendronate sodium tablets increase bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures) [see clinical studies (14.1) ]. alendronate sodium tablets are indicated for the prevention of postmenopausal osteoporosis [see clinical studies (14.2) ]. alendronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies (14.3) ]. alendronate sodium tablets are indicated for the treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density [see clinical studies (14.4) ]. alendronate sodium tablets are indicated for the treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget's disease of bone who have alkaline phosphatase at least two times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease [see clinical studies (14.5) ]. the optimal duration of use has not been determined. the safety and effectiveness of alendronate sodium tablets for the treatment of osteoporosis are based on clinical data of four years duration. all patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. patients who discontinue therapy should have their risk for fracture re-evaluated periodically. alendronate sodium tablets are contraindicated in patients with the following conditions: - abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia [see warnings and precautions (5.1) ] - inability to stand or sit upright for at least 30 minutes [see dosage and administration (2.6); warnings and precautions (5.1) ] - hypocalcemia [see warnings and precautions (5.2) ] - hypersensitivity to any component of this product. hypersensitivity reactions including urticaria and angioedema have been reported [see adverse reactions (6.2) ]. risk summary available data on the use of alendronate sodium in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. discontinue alendronate sodium when pregnancy is recognized. in animal reproduction studies, daily oral administration of alendronate to rats from before mating through the end of gestation or lactation showed decreased postimplantation survival and decreased pup body weight gain starting at doses equivalent to less than half of the highest recommended 40 mg clinical daily dose (based on body surface area, mg/m2 ). oral administration of alendronate to rats during organogenesis resulted in reduced fetal ossification starting at doses 3 times the 40 mg clinical daily dose. no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at doses equivalent to approximately 10 times the 40 mg clinical daily dose. delayed or failed delivery of offspring, protracted parturition, and late pregnancy maternal and fetal deaths due to maternal hypocalcemia occurred in rats at oral doses as low as one tenth the 40 mg clinical daily dose (see data) . bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. the amount of bisphosphonate incorporated into adult bone and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. the impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data reproduction studies in rats dosed orally from before mating to the end of gestation or lactation showed decreased postimplantation survival starting at 2 mg/kg/day and decreased body weight gain starting at 1 mg/kg/day, doses equivalent to less than half the 40 mg clinical daily dose based on body surface area, mg/m2 . incidence of incomplete fetal ossification in vertebral, skull, and sternebral bones were increased in rats dosed orally during organogenesis starting at 10 mg/kg/day (approximately 3 times the 40 mg clinical daily dose). no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at up to 35 mg/kg/day (equivalent to approximately 10 times the 40 mg clinical daily dose). both total and ionized calcium decreased in pregnant rats dosed orally with 15 mg/kg/day alendronate (approximately 4 times the 40 mg clinical daily dose) resulting in delays and failures of delivery. protracted parturition due to maternal hypocalcemia was observed when rats were treated from before mating through gestation starting at 0.5 mg/kg/day (approximately one tenth the 40 mg clinical daily dose). maternotoxicity (late pregnancy deaths) also occurred in female rats treated orally with 15 mg/kg/day (approximately 4 times the 40 mg clinical daily dose) for varying gestational time periods. these maternal deaths were lessened but not eliminated by cessation of treatment. calcium supplementation in the drinking water or by subcutaneous minipump to rats dosed orally with 15 mg/kg/day alendronate could not ameliorate the hypocalcemia or prevent the dystocia-related maternal and neonatal deaths. however, intravenous calcium supplementation prevented maternal, but not neonatal deaths. risk summary it is not known whether alendronate sodium is present in human breast milk, affects human milk production, or has effects on the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for alendronate sodium and any potential adverse effects on the breastfed child from alendronate or from the underlying maternal condition. alendronate sodium is not indicated for use in pediatric patients. the safety and efficacy of alendronate sodium were examined in a randomized, double-blind, placebo-controlled two-year study of 139 pediatric patients, aged 4 to 18 years, with severe osteogenesis imperfect (oi). one-hundred-and-nine patients were randomized to 5 mg alendronate, the free acid daily (weight less than 40 kg) or 10 mg alendronate, the free acid daily (weight greater than or equal to 40 kg) and 30 patients to placebo. the mean baseline lumbar spine bmd z-score of the patients was -4.5. the mean change in lumbar spine bmd z-score from baseline to month 24 was 1.3 in the alendronate sodium-treated patients and 0.1 in the placebo-treated patients. treatment with alendronate sodium did not reduce the risk of fracture. sixteen percent of the alendronate sodium patients who sustained a radiologically-confirmed fracture by month 12 of the study had delayed fracture healing (callus remodeling) or fracture non-union when assessed radiographically at month 24 compared with 9% of the placebo-treated patients. in alendronate sodium-treated patients, bone histomorphometry data obtained at month 24 demonstrated decreased bone turnover and delayed mineralization time; however, there were no mineralization defects. there were no statistically significant differences between the alendronate sodium and placebo groups in reduction of bone pain. the oral bioavailability in children was similar to that observed in adults. the overall safety profile of alendronate sodium in osteogenesis imperfecta patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with alendronate sodium. however, there was an increased occurrence of vomiting in osteogenesis imperfecta patients treated with alendronate sodium compared to placebo. during the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with alendronate sodium and 3 of 30 (10%) patients treated with placebo. in a pharmacokinetic study, 6 of 24 pediatric osteogenesis imperfecta patients who received a single oral dose of alendronate, the free acid 35 or 70 mg developed fever, flu-like symptoms, and/or mild lymphocytopenia within 24 to 48 hours after administration. these events, lasting no more than 2 to 3 days and responding to acetaminophen, are consistent with an acute-phase response that has been reported in patients receiving bisphosphonates, including alendronate sodium [see adverse reactions (6.2) ]. of the patients receiving alendronate sodium in the fracture intervention trial (fit), 71% (n = 2302) were greater than or equal to 65 years of age and 17% (n = 550) were greater than or equal to 75 years of age. of the patients receiving alendronate sodium in the united states and multinational osteoporosis treatment studies in women, osteoporosis studies in men, glucocorticoid-induced osteoporosis studies, and paget's disease studies [see clinical studies (14.1), (14.3), (14.4), (14.5) ], 45%, 54%, 37%, and 70%, respectively, were 65 years of age or over. no overall differences in efficacy or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. alendronate sodium is not recommended for patients with creatinine clearance less than 35 ml/min. no dosage adjustment is necessary in patients with creatinine clearance values between 35 to 60 ml/min [see clinical pharmacology (12.3) ]. as there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. no dosage adjustment is necessary [see clinical pharmacology (12.3) ].

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amneal pharmaceuticals of new york llc - nabumetone (unii: lw0tiw155z) (nabumetone - unii:lw0tiw155z) - nabumetone 500 mg - carefully consider the potential benefits and risks of nabumetone tablets usp and other treatment options before deciding to use nabumetone tablets usp. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). nabumetone tablets usp are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. nabumetone tablets are contraindicated in patients with known hypersensitivity to nabumetone or product excipients. nabumetone tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings , anaphylactoid reactions and precautions , general , preexisting asthma ). nabumetone tablets are contraindicated in the setting of coronary artery bypass graft (cabg) surgery (see warnings ).

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amneal pharmaceuticals of new york llc - oxymorphone hydrochloride (unii: 5y2ei94nbc) (oxymorphone - unii:9vxa968e0c) - oxymorphone hydrochloride 5 mg - oxymorphone hydrochloride extended-release tablets are 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 usage: - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve oxymorphone hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain. - oxymorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic. oxymorphone hydrochloride 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 (5.6)] - hypersensitivity (e.g. anaphylaxis) to oxymorphone, any other ingredients in oxymorphone hydrochloride extended-release tablets [see warnings and precautions (5.7), adverse reactions (6)]. - moderate and severe hepatic impairment [see warnings and precautions (5.9),  clinical pharmacology (12.3)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] 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 oxymorphone hydrochloride extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, reduced postnatal survival of pups and an increased incidence of stillborn pups were observed following oral treatment of pregnant rats with oxymorphone during gestation and through lactation at doses 2.4 and 12 times the human daily dose of 20 mg/day (hdd), respectively. reduced fetal weights were observed with oral administration of oxymorphone to pregnant rats and rabbits during organogenesis at exposures up to 4.9 and 48.8 times the hdd, respectively [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2% to 4% and 14% 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 may cause fetal-neonatal physical dependence and neonatal withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome, and manage accordingly [see warnings and precautions (5.4)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. oxymorphone hydrochloride extended-release tablets are not recommended for use in women during and immediately prior to labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including oxymorphone hydrochloride 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 oxymorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 5 mg/kg/day, 10 mg/kg/day or 25 mg/kg/day (2.4, 4.9, or 12.2 times the hdd based on body surface area, respectively). reduced mean fetal weights were observed at 4.9 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the high dose group). pregnant rabbits were treated with oxymorphone hydrochloride from gestation day 7 to 20 via oral gavage doses of 10 mg/kg/day, 25 mg/kg/day or 50 mg/kg/day (9.8, 24.4, or 48.8 times the hdd based on body surface area, respectively). decreased mean fetal weights were noted at 48.8 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights). pregnant rats were treated with oxymorphone hydrochloride from gestation day 6 to lactation day 20 via oral gavage doses of 1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day or 25 mg/kg/day (0.5, 2.4, 4.9, or 12.2 times the hdd based on body surface area, respectively). increased neonatal death (postnatal day 0 to 1) was noted at 2.4 times the hdd. decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain were noted at 4.9 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the 10 mg/kg/day and 25 mg/kg/day groups). in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of 153 mg/kg oxymorphone hydrochloride (62.2 times the hdd) on gestation day 8 to pregnant hamsters. this dose also produced significant maternal toxicity (20% maternal deaths). risk summary there is no information regarding the presence of oxymorphone in human milk, the effects on the breastfed infant, or the effects 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 oxymorphone hydrochloride extended-release tablets. clinical considerations monitor infants exposed to oxymorphone 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 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 [clinical pharmacology (12.2) and nonclinical toxicology (13.1)] . the safety and effectiveness of oxymorphone hydrochloride extended-release tablets in patients below the age of 18 years have not been established. two open-label studies were conducted in a total of 42 pediatric patients between the ages of 7 to 17 years requiring continuous, around the clock opioid treatment. the available safety and efficacy data were inconclusive for chronic use of oxymorphone hydrochloride extended-release tablets. limited data from one of the studies suggested that oxymorphone hydrochloride extended-release tablets is not recommended for post-surgical pain. of the total number of subjects in clinical studies of oxymorphone hydrochloride extended-release tablets, 27% were 65 and over, while 9% were 75 and over. no overall differences in effectiveness were observed between these subjects and younger subjects. there were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. these adverse events included dizziness, somnolence, confusion and nausea. on average, age greater than 65 years was associated with an increase in oxymorphone auc and cmax . initiate dosing with oxymorphone hydrochloride extended-release tablets in patients 65 years of age and over using the 5 mg dose and frequently reevaluate the patient for signs of respiratory and central nervous system depression when initiating and titrating oxymorphone hydrochloride extended-release tablets [see warnings and precautions (5.2)] . for patients on prior opioid therapy, start at 50% of the starting dose for a younger patient on prior opioids and titrate slowly. oxymorphone 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 the 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. patients with mild hepatic impairment have an increase in oxymorphone bioavailability compared to the subjects with normal hepatic function. in opioid-naïve patients with mild hepatic impairment, initiate oxymorphone hydrochloride extended-release tablets using the 5 mg dose and regularly evaluate closely for respiratory and central nervous system depression. oxymorphone hydrochloride extended-release tablets are contraindicated for patients with moderate and severe hepatic impairment [see dosage and administration (2.6), contraindications (4) , warnings and precautions (5.9)  and clinical pharmacology (12.3)] . for patients on prior opioid therapy, start at the 50% of the dose for that a patient with normal hepatic function on prior opioids and titrate slowly. patients with moderate to severe renal impairment were shown to have an increase in oxymorphone bioavailability compared to the subjects with normal renal function [see clinical pharmacology (12.3)] . start opioid-naïve patients with the 5 mg dose of oxymorphone hydrochloride extended-release tablets and titrate slowly while closely regularly evaluate for respiratory and central nervous system depression [see dosage and administration (2.6)] . for patients on prior opioid therapy, start at 50% of the dose for a patient with normal renal function on prior opioids and titrate slowly. oxymorphone hydrochloride extended-release tablets contain oxymorphone, a schedule ii controlled substance. oxymorphone hydrochloride extended-release tablets contain oxymorphone, 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 intentinal 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 to other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of oxymorphone hydrochloride extended-release 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 oxymorphone hydrochloride extended-release tablets with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of oxymorphone hydrochloride extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing oxymorphone, those with a history of drug or alcohol abuse, or those who use oxymorphone hydrochloride extended-release 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. pre-occupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. oxymorphone hydrochloride extended-release 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 oxymorphone hydrochloride extended-release tablets abuse of oxymorphone hydrochloride extended-release tablets poses a risk of overdose and death. this risk is increased with concurrent use of oxymorphone hydrochloride extended-release tablets with alcohol and/or other cns depressants. taking cut, broken, chewed, crushed or dissolved oxymorphone hydrochloride extended-release tablets enhance drug release and increases the risk of overdose and death. oxymorphone hydrochloride extended-release tablets is approved for oral use only. inappropriate intravenous, intramuscular, or subcutaneous use of oxymorphone hydrochloride extended-release tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e. a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue oxymorphone hydrochloride extended-release tablets in a patient physically dependent on opioids. rapid tapering of oxymorphone hydrochloride 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 oxymorphone hydrochloride extended-release tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxymorphone hydrochloride 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 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 (2.5)  and warnings and precautions (5.15)] . 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 of new york llc - metoclopramide hydrochloride (unii: w1792a2rvd) (metoclopramide - unii:l4yeb44i46) - metoclopramide 5 mg - the use of metoclopramide  tablets, usp is recommended for adults only. therapy should not exceed 12 weeks in duration. symptomatic gastroesophageal reflux:  metoclopramide tablets, usp are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy. the principal effect of metoclopramide is on symptoms of postprandial and daytime heartburn with less observed effect on nocturnal symptoms. if symptoms are confined to particular situations, such as following the evening meal, use of metoclopramide as single doses prior to the provocative situation should be considered, rather than using the drug throughout the day. healing of esophageal ulcers and erosions has been endoscopically demonstrated at the end of a 12-week trial using doses of 15 mg q.i.d. as there is no documented correlation between symptoms and healing of esophageal lesions, patients with documented lesions should be monitored endoscopically. diabeti

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amneal pharmaceuticals of new york llc - teriflunomide (unii: 1c058ikg3b) (teriflunomide - unii:1c058ikg3b) - teriflunomide tablets are indicated for the treatment of relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. teriflunomide tablets are contraindicated in/with: - patients with severe hepatic impairment [see warnings and precautions (5.1)] . - pregnant women and females of reproductive potential not using effective contraception. teriflunomide tablets may cause fetal harm [see warnings and precautions (5.2, 5.3) and use in specific populations (8.1)]. - patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablets. reactions have included anaphylaxis, angioedema, and serious skin reactions [see warnings and precautions (5.5)] . - co-administration with leflunomide [see clinical pharmacology (12.3)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women expos

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amneal pharmaceuticals llc - baclofen (unii: h789n3fke8) (baclofen - unii:h789n3fke8) - lioresal intrathecal (baclofen injection) is indicated for use in the management of severe spasticity. patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. for spasticity of spinal cord origin, chronic infusion of lioresal intrathecal via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable cns side effects at effective doses. patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy. lioresal intrathecal is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the fda specifically for the administration of lioresal intrathecal into the intrathecal space. spasticity of spinal cord origin: evidence supporting the efficacy of lioresal intrathecal was obtained in randomized, controlled investigations that compared the effects of either a single intrathecal dose or a three day intrathecal infusion of lioresal intrathecal to placebo in patients with severe spasticity and spasms due to either spinal cord trauma or multiple sclerosis. lioresal intrathecal was superior to placebo on both principal outcome measures employed: change from baseline in the ashworth rating of spasticity and the frequency of spasms. spasticity of cerebral origin: the efficacy of lioresal intrathecal was investigated in three controlled clinical trials; two enrolled patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. the first study, a randomized controlled cross-over trial of 51 patients with cerebral palsy, provided strong, statistically significant results; lioresal intrathecal was superior to placebo in reducing spasticity as measured by the ashworth scale. a second cross-over study was conducted in 11 patients with spasticity arising from brain injury. despite the small sample size, the study yielded a nearly significant test statistic (p= 0.066) and provided directionally favorable results. the last study, however, did not provide data that could be reliably analyzed. lioresal intrathecal therapy may be considered an alternative to destructive neurosurgical procedures. prior to implantation of a device for chronic intrathecal infusion of lioresal intrathecal, patients must show a response to lioresal intrathecal in a screening trial (see dosage and administration). hypersensitivity to baclofen. lioresal intrathecal is not recommended for intravenous, intramuscular, subcutaneous or epidural administration. drug preparation kit for use with medtronic ® synchromed implantable programmable infusion pumps instructions for use the lioresal® intrathecal (baclofen injection) drug preparation kit is used for kit models 8561, 8562, 8564, 8565 and 8566 to draw the drug from the ampule(s). the appropriate ampule(s) is/are placed within the corresponding kit. in addition, each kit contains: -syringe cap(s) -filter straw® tube(s) -ampule opener(s) -syringe label(s) -plastic bag -four gauze pads -20 ml syringe -lioresal® intrathecal (baclofen injection) prescribing information -drug preparation kit instructions for use indications the lioresal® intrathecal (baclofen injection) drug preparation kit is intended for use with medtronic synchromed implantable programmable infusion pumps. it is not for use with the medtronic minimed® infusion pumps. refer to the lioresal® lntrathecal (baclofen injection) drug prescribing information for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures.  contraindications refer to the contraindications listed in the appropriate pump technical manual, 856x refill kit instructions for use, and drug labeling. precautions if dilution of the drug is required, refer to the drug labeling for proper diluent and procedures. for emergency procedures, refer to the refill kit 856x instructions for use that are packaged with the refill kit. sterilization all components of the drug preparation kit are sterile. do not resterilize. should sterility be in question, discard and use a new kit. the outside of the ampule is sterile. if sterile technique is broken, the contents of the ampule are still sterile. instructions for use use sterile technique throughout the procedure to prevent contamination of the components and drug. note: the drug ampule is not sterile. 1. remove the drug ampule from the box. confirm drug ampule concentration prior to drug administration. 2. open the ampule as follows: note: the entire neck of the ampule is scored. an ampule opener has been provided to ease the opening of the ampule; always exercise caution when opening a glass ampule note: if the ampule opener is not used, use gauze pads to hold the top of the ampule when opening. figure 1.   a. hold the ampule in one hand and place opener (fins first) over the neck until it rests on the base portion of the ampule. grasp opener with forefinger and thumb while holding the ampule base. hold ampule upright and snap. dispose of opener and ampule top to prevent potential contamination (figure 1).  3. assemble the syringe and filter straw® tube (figure 2), making sure the syringe connection is snug to avoid leakage. figure 2. assemble syringe and filter straw® tube 4.withdraw the drug from the ampule(s) (figure 3). figure 3. withdraw drug from ampule 5.remove the filter straw® tube from the syringe. appropriately discard filter straw® tube. 6.purge the air from the syringe. 7. if drug syringe is to be transferred prior to procedure a syringe cap has been provided. attach the syringe cap, making sure the cap is snug to avoid leakage. 8. for convenience, a syringe label has been provided to capture patient's name, drug name, drug concentration, and date. 9. peel the backing from the label and attach the label to the syringe, making sure not to cover the volume indicators on the syringe (figure 4). figure 4. syringe with cap and label 10.  if the drug needs to be transported, place the syringe(s) in the plastic bag. 11.  if applicable, repeat steps 1 – 10 with the second syringe, filter straw® tube, syringe cap, and syringe label supplied in the model 8562, 8565 and 8566 kits. 12. refer to the 856x refill kit instructions for use for pump refill instructions. note: purge air from syringe prior to drug administration. rx only medtronic® and minimed® are trademarks of medtronic® and are registered in the u.s. and possibly other countries. lioresal® is a registered trademark of amneal filter straw® is a registered trademark of b.braun medical inc. amneal pharmaceuticals llc bridgewater, nj  08807 rev. 03-2023-00 amneal refill kit 856x for use with medtronic synchromed® implantable programmable infusion pumps instructions for use rx only explanation of symbols on product or package labeling refer to the appropriate product for symbols that apply. open here table of contents   introduction 7 package contents 7 indications 7 contraindications 7 warnings 7 precautions 11 adverse events 12 instructions for use 12 sterilization 12 preliminary procedures 12 emptying the synchromed pump 13 refilling the synchromed pump 16 programming the synchromed pump 19 after the refill procedure 19 reservoir rinse procedure 19 performing a reservoir rinse 19 technical support 20 emergency procedures 20 lioresal intrathecal (baclofen injection) overdose 20 lioresal intrathecal (baclofen injection) underdose/withdrawal 21 emergency procedure to empty pump reservoir 22 special notice 23 limited warranty 24 amneal model 856x refill kit limited warranty 24 refer to the indications, drug stability, and emergency procedures reference manual1 for indications and related information. refer to the appropriate information for prescribers booklet for contraindications, warnings, precautions, adverse events summary, individualization of treatment, patient selection, use in specific populations, and component disposal. refer to the lioresal intrathecal (baclofen injection) drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures. 1 the referenced manual is available from the medtronic website. to view, download, print, or order the manual, go to www.medtronic.com/manual or contact your medtronic representative. introduction these instructions include only the procedure for refilling the pump reservoir with lioresal intrathecal (baclofen injection). refer to the appropriate technical manuals, provided by the manufacturer for instructions on implanting and/or programming of the pump. package contents the model 856x refill kit contains the following sterile components that are not made with natural rubber latex: - two 22-gauge noncoring needles - extension set with a clamp - 0.2-micron filter - 20-ml syringe - template - fenestrated drape with adhesive strips - accessories (adhesive bandage, sharps plug, four gauze pads, two alcohol wipes, gloves, povidone iodine swab sticks) - refill kit instructions for use - sterile drape indications the model 856x refill kit is intended for use in refilling medtronic synchromed implantable programmable infusion pumps. it is not for use with the medtronic minimed infusion pumps. contraindications amneal refill kits are contraindicated for all catheter access port procedures. warnings withdrawal - abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death. prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. special attention should be given to patients at apparent risk (e.g. spinal cord injuries at t-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen). consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information. user instructions - comply with all product instructions for initial preparation and filling, implantation, programming, refilling, and accessing the catheter access port (if present) of the pump. failure to comply with all instructions can lead to technical errors or improper use of implanted infusion pumps and result in additional surgical procedures, a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose. implantation and system management - implantation and ongoing system management must be performed by individuals trained in the operation and handling of the infusion system and must be in compliance with procedures described in the appropriate technical instructions. inadequate training or failure to follow instructions can require surgical revision or replacement, and result in a clinically significant or fatal drug underdose or overdose. overinfusion – overinfusion is defined as the delivery of more drug volume than the programmed rate, exceeding the pump’s flow rate accuracy specification. pump reservoir contents aspirated during a refill procedure that are less than expected may indicate that the pump has overinfused. overinfusion may or may not be associated with clinically relevant symptoms. when the pump delivers more drug volume than the programmed rate, patients may experience overdose symptoms, and the pump reservoir will deplete more quickly than expected. patients may experience underdose or withdrawal symptoms if the drug is depleted prior to the scheduled refill date from an overinfusing pump. at each refill visit, question and examine the patient for signs and symptoms of overdose, underdose, and withdrawal. the low reservoir alarm of an overinfusing pump will not sound if the pump reservoir is prematurely depleted. the low reservoir alarm is calculated from the pump’s programmed delivery rate and is not a direct measurement of the actual drug volume in the pump reservoir. multiple factors may increase the likelihood of overinfusion, including: nonindicated drug formulations, overfilling of the pump reservoir, operation of the pump with no fluid in the reservoir, catheter occlusion, and pump stops or motor stalls lasting more than 48 hours. refer to the appropriate drug labeling for specific drug underdose or overdose symptoms and methods of management. if overinfusion is strongly suspected, contact medtronic. reducing the dose and/or concentration is not recommended as a solution for overinfusion. if immediate discontinuation of therapy is clinically appropriate for the patient, program the pump to minimum rate mode, and aspirate any remaining drug from the reservoir. five occurrences of overinfusion have been identified in medtronic’s prospective, long-term multi-center registry study (product surveillance registry) as of january 2016, resulting in a rate estimate of less than 0.14% (approximately 1 in 700). calculating catheter volume - use the catheter length recorded at implant or catheter revision when calculating catheter volume. the actual implanted catheter length and catheter model number are required to accurately calculate catheter volume. a universal value does not exist that can be used as a substitute for this knowledge. an inaccurate catheter volume calculation can result in a clinically significant or fatal drug underdose or overdose. contrast medium (pumps with a catheter access port) - do not inject any contrast medium into the pump reservoir. injecting contrast medium into the pump reservoir can impair pump operation. refill - patients must return to the clinic for refills at the prescribed times. failure to return to the clinic for refills at the prescribed times can result in the actual flow rate of the pump being less than expected, resulting in a loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose. failure to return at the prescribed times can also damage the pump, requiring surgical replacement. refill kit components - use the appropriate amneal refill kit during all lioresal refill procedures using medtronic implantable infusion pumps. using components other than amneal components or a kit other than the appropriate refill kit can damage medtronic pump components, requiring surgical revision or replacement, and allow drug leakage into surrounding tissue, resulting in loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose. injection error during a pump refill procedure - be certain you are accessing the reservoir fill port when injecting fluids into an implanted pump. always: - identify the pump model and reservoir volume. - identify the location of the reservoir fill port. – avoid pocket fill, ie, improper injection of medication into the subcutaneous tissue (see below). – avoid inadvertent injection into the catheter access port (see below). - use the instructions, noncoring needles, appropriate template edge, and other accessories provided in the appropriate kit. - verify the location of the reservoir fill port during needle insertion according to the instructions provided and using other medical procedures as appropriate. - refer to the drug labeling for indications, contraindications, warnings, precautions, adverse events, and dosage and administration information. pocket fill is the improper injection of refill medication into the subcutaneous tissue, which includes the pump pocket. the injection of drug into the subcutaneous tissue can lead to an acute systemic overdose, which can be fatal. after a pocket fill, the pump reservoir will become empty sooner than anticipated, and this may cause underdose symptoms and/or baclofen withdrawal syndrome, which can be fatal. if it is suspected or known that all or part of the drug was injected into the pocket during the refill procedure, monitor the patient closely for signs and symptoms of overdose in an appropriate facility for a sufficient amount of time or until the symptoms have resolved. refer to the refill kit manual or the indications, drug stability, and emergency procedures reference manual1 for emergency procedures associated with drug underdose and overdose. refer to the drug product information label for specific drug underdose and overdose symptoms and methods of management. inadvertent injection into the catheter access port may result in a clinically significant or fatal drug overdose. if it is suspected or known that all or part of the drug was injected into the catheter access port during the refill procedure, monitor the patient closely for signs and symptoms of overdose in an appropriate facility for a sufficient amount of time or until the symptoms have resolved. refer to the catheter access port kit manual or the indications, drug stability, and emergency procedures reference manual1 for emergency procedures associated with drug overdose. refer to the drug labeling for specific drug overdose symptoms and methods of management. changing drug or decreasing drug concentrations - rinse the reservoir twice between solutions when changing drug or decreasing drug concentrations in the pump reservoir. a significant amount of drug may be present in the pump reservoir after emptying the pump. this residual volume cannot be removed by emptying the pump. rinsing the reservoir between solutions minimizes the amount of drug in this residual volume but does not eliminate it. failure to account for residual drug in the pump reservoir can result in a concentration that is different than intended and a clinically significant or fatal drug underdose or overdose. program a bridge bolus after rinsing the reservoir twice.the bridge bolus advances the remaining old drug (the drug left in the pump tubing, catheter access port, and catheter after emptying and refilling the pump) to the catheter tip at the specified flow rate. refer to "performing a reservoir rinse" on page 18 of this manual. refer to the programming guide for bridge bolus procedures. connections - firmly secure all connections. failure to secure connections can allow drug to leak onto the surrounding skin and may result in inadequate therapy or infection. reservoir fill port injections - do not use excessive force when accessing the reservoir fill port. excessive force can result in damage to the needle or pump requiring surgical revision or replacement, and leakage into surrounding tissue, resulting in loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose. intrathecal therapy - for intrathecal therapy, use only a preservative-free sterile solution indicated for intrathecal use. nonindicated fluids containing preservatives or endotoxins can be neurotoxic in intrathecal applications. using nonindicated fluids can result in adverse events including, but not limited to, extreme pain, cramps, seizures, and death. drug information - refer to the drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures. refer to the drug labeling for specific drug underdose or overdose symptoms and methods of management. failure to refer to the drug labeling can result in inappropriate patient selection and management, inadequate therapy, intolerable side effects, or a clinically significant or fatal drug underdose or overdose. consider the possibility of a drug error if the patient experiences unusual side effects. failure to do so can result in misdiagnosis of patient symptoms. mixing drugs - the effects that drug mixtures have on pump operation are unknown. drugs can precipitate when mixed. these precipitates can inhibit pump flow or block the catheter, resulting in loss of therapy or a clinically significant or fatal drug underdose. drug interaction and side effects - inform patients of the appropriate warnings and precautions regarding drug interactions, potential side effects, and signs and symptoms that require medical attention, including prodromal signs and symptoms of inflammatory mass. failure to recognize the signs and symptoms and to seek appropriate medical intervention can result in serious patient injury or death. drug overdose symptoms and management - refer to the emergency procedures included at the end of this manual and the drug labeling for specific drug overdose symptoms and methods of management. drug underdose/overdose - inform patients and caregivers of the signs and symptoms of a drug underdose and overdose. inform patients and caregivers: - to be aware and report any unusual signs or symptoms at anytime during or after a refill or catheter access port procedure. - to be alert for any burning sensations in the area of the pump pocket during their refill or catheter access port procedure. - to especially watch for signs of underdose and overdose. - to stay alert for signs or symptoms that may indicate changes to their prescribed drug concentration or programmed dose. - to seek emergency assistance as necessary. refer to the refill kit or catheter access port kit manual or the indications, drug stability and emergency procedures reference manual1 for emergency procedures associated with drug underdose and overdose. failure to recognize these signs and symptoms and to seek appropriate medical intervention can result in serious patient injury or death. patient travel – patients should notify their clinicians of any travel plans. clinicians need this information to coordinate patient care and pump refills and help prevent a loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose. precautions compatibility, all components - follow these guidelines when selecting system components: - amneal components: for proper therapy, use only components that are compatible with the appropriate indication. - non-amneal components: no claims of safety, efficacy, or compatibility are made with regard to the use of non-amneal components. refer to the non-amneal component documentation for information. component packaging - before shipment the components in the sterile package were sterilized by the process indicated on the package label. do not use or implant a component if the following circumstances have occurred: - the storage package or sterile seal has been pierced or altered because component sterility cannot be guaranteed and infection may occur. - the component shows signs of damage because the component may not function properly. - the use-by date has expired because component sterility cannot be guaranteed and infection may occur; also, device battery longevity may be reduced and may require early replacement. storage temperature: kits and accessories - do not store or transport the kit device components or accessories above 57 °c (135 °f) or below –34 °c (–30 °f). temperatures outside this range can damage device components. aseptic technique - use strict aseptic technique when accessing the reservoir fill port or the catheter access port of an implanted pump. failure to use aseptic technique can contaminate fluids or tissues and result in local or systemic infection. infection - use extreme caution when accessing the reservoir fill port or catheter access port of the implanted pump if local or systemic infection is suspected. avoid contaminating the system or further spreading the infection. local or systemic infection may require pump revision or removal. therapy discontinuance - if therapy is discontinued for an extended period, fill the pump reservoir with preservative-free saline. program the pump to infuse at the minimum flow rate. refill the pump as needed to ensure the pump always contains fluid in the reservoir and fluid pathway. stopping the pump for extended periods or allowing the pump reservoir to empty completely can damage the system and require surgical replacement. single use only - do not reuse any component. components are intended for single use only. reusing components can result in inadequate therapy and an increased risk of infection. reservoir valve activation - do not prematurely activate the pump reservoir valve. activation of the pump reservoir valve seals the pump reservoir valve closed. unusual resistance or the inability to inject the entire fill volume may indicate activation of the pump reservoir valve. if the valve closes, a portion of the reservoir contents must be delivered or removed before filling can be completed, and procedural delays can occur. activation of the pump reservoir valve before the pump is filled can be resolved by the following actions: - completely aspirating all contents of the pump reservoir before filling - not allowing air into the pump reservoir through an open needle in the septum or an unclamped extension - not exceeding the maximum reservoir volume indicated in the pump labeling - if the patient has a fever, waiting for the patient’s fever to reduce to 38°c or below adverse events the adverse events associated with the use of this device may include, but may not be limited to, the following: - meningitis - infection - reservoir contamination - overpressurization of the reservoir - injection into pocket or subcutaneous tissue - activation of reservoir valve instructions for use become thoroughly familiar with all product literature before using this refill kit. sterilization all components of the kit are sterile. do not resterilize. should sterility of the kit be in question, discard and use a new kit. note: the outside of the ampule is sterile. if sterile technique is broken, the contents of the ampule are still sterile. preliminary procedures - open the lioresal refill kit - prepare the sterile field. the sterile drape can be used to prepare the sterile field. - gather the following sterile equipment: - drug prep kit containing correct concentration and volume of lioresal intrathecal (baclofen injections) - sterile drape from the refill kit: - 20-ml empty syringe - extension set with a clamp - template - 0.2-micron filter - two 22-gauge noncoring needle (2", 1.5") - fenestrated drape with adhesive strips - two alcohol wipes -  latex-free sterile gloves - adhesive bandage, optional - *note: the sharps plug should remain in the kit tray to receive the used sharps, if desired 4. refer to the drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures. 5. prepare the programmer for use. refer to the appropriate programming guide for instructions. 6. confirm the: - pump model - reservoir volume (i.e., expected volume) - location of the pump note: the model and reservoir volume can be confirmed by the programmer. alternatively, a radiopaque identifier in the pump shows the pump model and identifies medtronic as the pump manufacturer on a standard x-ray (figure 1). a three-letter code designates the pump model. figure 1. a radiopaque identifier on a synchromed ii pump.     5. confirm that the volume of the prescribed fluid does not exceed the reservoir volume of the pump. emptying the synchromed pump - prepare the injection site by cleansing the area. - open the kit. put on sterile gloves. - place the drape, exposing the pump site. - using sterile procedures, assemble the needle, extension set, and empty syringe as follows: a. connect the empty syringe to the extension set. b. connect the needle to the extension set. 5. palpate the pump and identify the location of the catheter access port and the edges of pump. factors that may make it difficult to locate the pump include, but are not limited to: - deep implant - patient position (eg, a seated patient) - scar tissue at the pump implant site - seroma - the pump is tilted in the pocket - ·obesity - pump movement within the pocket - weight gain after implant - weight loss after implant if you have difficulty identifying the pump features, you may seek assistance from another clinician. if deemed necessary by the clinician, x-ray and fluoroscopy can be used to assist in locating or determining the orientation of the pump. 6. place the template on the skin over the pump, and align the refill template. align the right edge of the template with the right edge of the pump (figure 2). use the center circle of the template to insert the needle into the reservoir fill port. figure 2. aligning the refill template. 7. close the clamp. 8. gently insert the 22-gauge needle perpendicular to the surface of the pump through the center of the template and into the center of the reservoir fill port until the needle touches the bottom of the reservoir fill port (figures: 3 – 4). note: the pump may be tilted within the pocket and therefore the needle angle may not be perpendicular to the patient's body. during proper needle insertion, you will feel the needle: - pass through the patient's skin and subcutaneous tissue, - hit the silicone septum, (scar tissue, if present, can feel similar to the septum.) - pass through the septum, and - hit the metal bottom of the reservoir fill port. (the top of the pump is metal and hitting the top of the pump can feel similar to hitting the bottom of the reservoir fill port.) if excessive resistance is encountered during needle insertion, reassess placement. do not force the needle. the feel of abnormal resistance during the procedure may be an indication that the needle is not in the center of the reservoir fill port. figure 3. view inside of a synchromed programmable pump while the needle is fully and properly inserted. figure 4. close the clamp and insert the needle into the reservoir fill port.   note: at any point during the procedure, if in doubt about the needle location, reassess its position. factors that may contribute to difficulty inserting the needle into the reservoir fill port include, but are not limited to: - the pump is flipped in the pocket - deep implant - patient position (eg, a seated patient) - patient movement (eg, spasticity, difficulty hold still) - localized muscle spasms at the pump implant site - scar tissue at the pump implant site - seroma - the pump is tilted in the pocket - obesity - pump movement within the pocket - weight gain after implant - weight loss after implant 9. open the clamp and slowly withdraw the fluid from the reservoir into the empty syringe. note: if the withdrawn fluid has an unexpected appearance (eg, evidence of blood), this may indicate that the needle is not properly inserted into the pump. 10. if the syringe maximum capacity is reached before the reservoir is completely empty, more than one syringe will be needed to empty the pump. a. close the clamp. b. remove the full syringe. c. attach an empty syringe. d. verify that the needle is in the pump reservoir fill port. e. repeat step 9, then continue to step 11. 11. completely empty the pump. when the pump is empty, the bubbles will stop forming, and negative pressure in the syringe can be felt. 12. close the clamp and remove the syringe from the extension set. note: keep the needle in the reservoir fill port and the clamp closed for the pump refill procedure that follows. 13. note the amount withdrawn from the pump for entry in the patient's record. 14. compare the amount withdrawn from the pump to the expected volume. see the pump programmer for the expected volume. the amount withdrawn should approximately equal the expected volume. if a less than expected volume is observed, potential causes of the volume discrepancy could include: inaccurate volume measurements, incomplete pump aspiration, incorrect volume entry into clinician programmer at refills, unrecognized partial pocket fill, aspiration of pump medication by patient or caregiver, or overinfusion. note: immediately following the refill procedure: − record the amount withdrawn and the expected volume in the patient’s record − record any volume discrepancy and compare volume discrepancies from visit to visit. 15. discard the fluid and syringe as appropriate for the fluid content in accordance with institutional policies and applicable regulations. refilling the synchromed pump warning: overinfusion is defined as the delivery of more drug volume than the programmed rate, exceeding the pump’s flow rate accuracy specification. pump reservoir contents aspirated during a refill procedure that are less than expected may indicate that the pump has overinfused. overinfusion may or may not be associated with clinically relevant symptoms. when the pump delivers more drug volume than the programmed rate, patients may experience overdose symptoms, and the pump reservoir will deplete more quickly than expected. patients may experience underdose or withdrawal symptoms if the drug is depleted prior to the scheduled refill date from an overinfusing pump. at each refill visit, question and examine the patient for signs and symptoms of overdose, underdose, and withdrawal. the low reservoir alarm of an overinfusing pump will not sound if the pump reservoir is prematurely depleted. the low reservoir alarm is calculated from the pump’s programmed delivery rate and is not a direct measurement of the actual drug volume in the pump reservoir. multiple factors may increase the likelihood of overinfusion, including: nonindicated drug formulations, overfilling of the pump reservoir, operation of the pump with no fluid in the reservoir, catheter occlusion, and pump stops or motor stalls lasting more than 48 hours. refer to the appropriate drug labeling for specific drug underdose or overdose symptoms and methods of management. if overinfusion is strongly suspected, contact medtronic. reducing the dose and/or concentration is not recommended as a solution for overinfusion. if immediate discontinuation of therapy is clinically appropriate for the patient, program the pump to minimum rate mode, and aspirate any remaining drug from the reservoir. five occurrences of overinfusion have been identified in medtronic’s prospective, long-term multi-center registry study (product surveillance registry) as of january 2016, resulting in a rate estimate of less than 0.14% (approximately 1 in 700). warning: pocket fill is the improper injection into the subcutaneous tissue, which includes the pump pocket. pocket fill can result in a loss of or change in symptom control, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose. observe the patient after the pump refill procedure for any signs or symptoms that could indicate a pocket fill or any other drug-related adverse event due to the refill procedure. inadvertent injection into the catheter access port may result in a clinically significant or fatal drug overdose. observe the patient after the pump refill procedure for any signs or symptoms that could indicate a drug-related adverse event due to the pump refill procedure. warning: if it is suspected or known that all or part of the drug was inadvertently injected into the pocket or the catheter access port during the refill procedure, monitor the patient closely for signs and symptoms of overdose in an appropriate facility for a sufficient amount of time or until the symptoms have resolved. refer to the kit manual or the indications, drug stability, and emergency procedures reference manual1 for emergency procedures associated with drug underdose and overdose. refer to the drug product information label for specific drug underdose and overdose symptoms and methods of management. warning: swelling at the injection site may indicate that the needle tip is not properly located within the pump reservoir, and the result could be pocket fill. pocket fill can result in a loss of or change in symptom control, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose. absence of swelling does not in all cases demonstrate that the needle tip is properly located. if swelling is present, stop injecting and observe the patient for any signs or symptoms that could indicate a pocket fill or any other drug-related adverse event. - if changing drug or drug concentrations, refer to "performing a reservoir rinse" on page 18. otherwise, proceed to the next step. - confirm that the refill volume of the prescribed fluid does not exceed the reservoir volume of the pump. - purge the air from the syringe containing the prescribed fluid. - attach the filter to the syringe with the prescribed fluid. - purge all air from the filter. - attach the syringe with the prescribed fluid and filter to the extension set (figure 5). - before and during injection, verify that the needle remains fully inserted to the bottom of the reservoir fill port. do not apply tension to the extension tubing because the needle may be pulled out from the reservoir. - open the clamp and as the clamp is opened, observe the following indications that the needle continues to be properly positioned: the bubbles in the extension set are immediately drawn into the pump. the plunger may move slightly when the drug is initially drawn into the pump. - the bubbles in the extension set are immediately drawn into the pump. - the plunger may move slightly when the drug is initially drawn into the pump. - slowly depress the plunger on the syringe to inject the prescribed fluid into the pump reservoir. while injecting the prescribed fluid, verify that the needle remains properly located within the reservoir (figure 5). a. periodically withdraw and observe a portion of the drug to confirm that the drug has the expected appearance. b. after confirming that the needle remains in the reservoir, resume injecting fluid. figure 5. open the clamp and inject into the pump reservoir.   caution: if you encounter unusual resistance before the maximum reservoir volume is injected or you are unable to inject fluid, the reservoir valve may have been activated. activation of the pump reservoir valve seals the pump reservoir valve closed. if the valve closes, a portion of the reservoir contents must be delivered or removed before filling can be completed, and procedural delays can occur. to prevent activation of the pump reservoir valve during emptying and filling procedures: - completely aspirate all contents of the pump reservoir before filling; - do not allow air into the pump reservoir through an open needle in the septum or an unclamped extension; and - do not exceed the maximum reservoir volume indicated in the pump labeling. 10. if you have activated the reservoir valve, complete steps a – g below. otherwise, proceed to step 11. a. discontinue injection. b. close the clamp. c. remove the syringe with prescribed fluid and attached filter. d. attach an empty 20-ml syringe to the extension set. e. open the clamp, and aspirate until all fluid/air is removed. f. close the clamp and remove the syringe containing the aspirate from the extension set and discard the syringe. g. repeat steps 2 – 10. note:  for pumps with a reservoir valve, the amount of time before the valve will release is dependent on the duration and the amount of pressure applied after the valve is first activated. the more pressure exerted, the longer it may take to release the valve. 11. if more than one syringe of prescribed fluid is needed to fill the pump reservoir, complete steps a – d below. otherwise, proceed to step 12. a. close the clamp. b. keep the filter from the extension set in place, and remove the first syringe from the filter. caution: do not remove the filter from the extension set. removal of the filter could compromise the sterile barrier, which could result in an infection for the patient. c. purge the air from the second syringe, and attach the second syringe to the filter (figure 5). d. with the second syringe in a vertical position, open the clamp and slowly depress the plunger on the syringe to inject the prescribed fluid into the pump reservoir. 12. when filling is complete, close the clamp and carefully remove the needle from the reservoir fill port. note: if you are unsure whether drug was injected correctly into the pump, completely aspirate the pump to verify that all of the injected drug can be removed. 13. remove the cleansing agent from the patient’s skin using an alcohol pad. 14. apply an adhesive bandage, if desired. 15. discard all components of the kit. programming the synchromed pump - if the drug concentration or drug has been changed, program a bridge bolus. refer to the programming guide for the pump software. - if any prescription information has changed, enter the changed information into the clinician programmer: for example drug name, drug concentration, infusion information, or volume of prescribed fluid in the pump reservoir. - update the pump. after the refill procedure - record the amount withdrawn and the expected volume in the patient’s record. - record any volume discrepancy and compare volume discrepancies from visit to visit. - print out the desired refill-related reports, and place the final pump settings in the patient file. - determine the refill date from the printout, and schedule a refill appointment reservoir rinse procedure   performing a reservoir rinse to prevent drug overdose or underdose when changing concentrations or changing solutions in the pump reservoir, always rinse the reservoir twice between solutions to remove the drug that remains in the reservoir after emptying the pump. this remaining volume is known as the residual volume. the procedure for performing a reservoir rinse is outlined below. use the components of the appropriate refill kit to perform the rinse and follow the applicable empty and refill procedures for that kit. - empty the pump completely. - fill the pump with 10 ml of sterile preservative-free sodium chloride injection, usp. - empty the pump completely. - repeat steps 2 and 3. - fill the pump to capacity with the prescribed fluid. - program a bridge bolus. refer to the programming guide for the pump software. technical support   a toll-free technical support service is available 24 hours a day for clinicians managing patients with medtronic implantable infusion pumps. telephone customer service at: 1-800-707-0933. emergency procedures lioresal intrathecal (baclofen injection) overdose consult the patient's medical record or with the patient's physician to confirm the drug or drug concentration within the pump reservoir. symptoms drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, hypothermia, seizures, rostral progression of hypotonia, and loss of consciousness progressing to coma. there is no specific antidote for treating overdoses of intrathecal baclofen injection.   actions   see table 1. table 1. lioresal intrathecal (baclofen injection) overdose emergency procedures   maintain airway/breathing/circulation. intubation and respiratory support may be necessary. ↓ empty pump reservoir to stop drug flow. record amount withdrawn. ↓ ↓ ↓ if not contraindicated, withdraw 30 – 40 ml csf by lumbar puncture or through the catheter access port to reduce the concentration of baclofen in the csf. use only a 24-gauge or smaller, 1.5- or 2.0-inch (3.8- or 5.1-cm), needle for withdrawal from the catheter access port.a proceed immediately to the next step. ↓ ↓ notify patient's physician managing intrathecal baclofen injection therapy. ↓ continue to monitor closely for symptom recurrence. ↓ report incident to amneal a use a 24- or 25-gauge needle for withdrawal from a synchromed ii catheter access port. lioresal intrathecal (baclofen injection) underdose/ withdrawal   consult the patient's medical record or with the patient's physician to confirm the drug or drug concentration within the pump reservoir. symptoms of underdose pruritus without rash, hypotension, paresthesia, fever, and altered mental state. priapism may develop or recur if treatment with intrathecal baclofen is interrupted. symptoms of withdrawal exaggerated rebound spasticity and muscle rigidity, rhabdomyolysis, and multiple organ failure. the condition may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, and neuroleptic- malignant syndrome. actions see table 2. table 2. lioresal intrathecal (baclofen injection) underdose/withdrawal emergency procedures initiate life-sustaining measures if indicated. ↓ if a patient receiving intrathecal baclofen injection presents with the signs and symptoms suggestive of withdrawal, the following is consistent with that suggested by a panel of therapy-experienced clinicians convened to explore this issue. a,b - immediately contact a physician experienced in intrathecal baclofen injection, preferably the physician managing the therapy for the patient in question; follow the recommendations of this physician. this step is important even if the patient’s signs and symptoms seem mild. - if a physician experienced in intrathecal baclofen injection is unavailable, consider instituting one or more of the following options, unless otherwise contraindicated: - high-dose oral* or enteral baclofen - restoration of intrathecal baclofen injection infusion - intravenous benzodiazepines by continuous or intermittent infusion, titrating the dosage until the desired therapeutic effect is achieved * note: oral baclofen should not be relied upon as the sole treatment for intrathecal baclofen injection withdrawal syndrome. ↓ report incident to amneal a refer to the drug manufacturer’s package insert for a complete list of indications, contraindications, warnings, precautions, adverse events, and dosage and administration information. b coffey rj, edgar ts, francisco ge, et al. abrupt withdrawal from the intrathecal baclofen: recognition and management of a potentially life- threatening syndrome. arch phys med rehabil. 2002;83:735-741. emergency procedure to empty pump reservoir   equipment   - 22-gauge noncoring needle - 20-ml syringe - 3-way stopcock or extension set with clamp - antiseptic agent - assemble the needle, syringe, and stopcock or extension set. - locate the pump by palpation. the reservoir fill port is located in the center of the pump. if you have difficulty identifying the pump features, you may seek assistance from another clinician. if deemed necessary by the clinician, x-ray and fluoroscopy can be used to assist in locating or determining the orientation of the pump. 3. prepare the injection site by cleansing the area using an antiseptic agent. 4. gently insert the 22-gauge noncoring needle into the center of the reservoir fill port until the needle touches the bottom of the reservoir fill port (figure 6). during proper needle insertion, you will feel the needle: - pass through the patient's skin and subcutaneous tissue, - hit the silicone septum, (scar tissue, if present, can feel similar to the septum.) (scar tissue, if present, can feel similar to the septum.) - pass through the septum, and - hit the metal bottom of the reservoir fill port. (the top of the pump is metal and hitting the top of the pump can feel similar to hitting the bottom of the reservoir fill port.) if excessive resistance is encountered during needle insertion, reassess placement. do not force the needle. the feel of abnormal resistance during the procedure may be an indication that the needle is not in the center of the reservoir fill port. figure 6. view inside of a synchromed programmable pump while the needle is fully and properly inserted. 5. open the clamp or stopcock and slowly withdraw the fluid from the reservoir into the empty syringe. 6. depending on pump reservoir volume, more than one syringe may be needed to empty the pump. close the clamp or stopcock when changing syringes. 7. completely empty the pump. when the pump is empty, the bubbles will stop forming, and negative pressure in the syringe can be felt. 8. remove the needle from the reservoir fill port. 9. record in patient chart the amount of fluid emptied from the pump reservoir. special notice the amneal model 856x refill kit is designed to be used for refilling medtronic implantable programmable infusion pumps with the exception of medtronic minimed infusion pumps. amneal cannot warrant or guarantee the refill kit because, despite the exercise of all due care in design, component selection, manufacture, and testing prior to sale, the components of the refill kit may be easily damaged before or during use by improper handling or other intervening acts. amneal model 856x refill kit limited warranty1 a. this limited warranty provides the following assurance to the purchaser of the amneal model 856x packaged herein, hereafter referred to as the “product”: - should the product fail to function within normal tolerances due to a defect in materials or workmanship prior to its "use by" date, amneal will at its option: (a) issue a credit to the purchaser equal to the purchase price, as defined in subsection a(2), against the purchase of the replacement product or provide a functionally comparable replacement product at no charge. - as used herein, purchase price shall mean the lesser of the net invoiced price of the original, or current functionally comparable, or replacement product. b. to qualify for the limited warranty set forth in section a(1), the following conditions must be met: - the product must be used prior to its "use by" date. - the unused portion of the product must be returned to amneal within thirty (30) days after discovery of the defect and shall be the property of amneal. - the product must not have been altered or subjected to misuse, abuse or accident. - the product must be used in accordance with the labeling and instructions for use provided with the product. c. this limited warranty is limited to its express terms. in particular: - except as expressly provided by this limited warranty, amneal is not responsible for any direct, incidental or consequential damages based on any defect, failure or malfunction of the product, whether the claim is based on warranty, contract, tort or otherwise. - this limited warranty is made only to the purchaser who uses the product. as to all others, amneal makes no warranty, express or implied, including, but not limited to, any implied warranty of merchantability or fitness for a particular purposewhether arising from statute, common law, custom or otherwise. no express or impliedwarranty to the patient shall extend beyond the period specified in a(1) above. this limitedwarranty shall be the exclusive remedy available to any person. - the exclusions and limitations set out above are not intended to, and should not be construed so as to contravene mandatory provisions of applicable law. if any part or term of this limited warranty is held to be illegal, unenforceable or in conflict with applicable law by a court of competent jurisdiction, the validity of the remaining portions of the limited warranty shall not be affected, and all rights and obligations shall be construed and enforced as if this limited warranty did not contain the particular part or term held to be invalid. this limited warranty gives the patient specific legal rights. the patient may also have other rights which vary from state to state. - no person has any authority to bind amneal to any representation, condition or warranty except this limited warranty. 1 this limited warranty is provided by amneal. it applies only in the united states. medtronic® , isomed® , synchromed® , and medtronic logo are trademarks of medtronic. minimed® is a registered trademark of medtronic minimed, inc. lioresal® is a registered trademark of amneal amneal pharmaceuticals llc bridgewater, nj  08807 rev. 03-2023-00

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

amneal pharmaceuticals llc - carboprost tromethamine (unii: u4526f86fj) (carboprost - unii:7b5032xt6o) - carboprost tromethamine injection is indicated for aborting pregnancy between the 13th and 20th weeks of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: 1.   failure of expulsion of the fetus during the course of treatment by another method; 2.   premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; 3.   requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; 4.   inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion. carboprost tromethamine injection is indicated for the treatment of postpartum hemorrhage due to uterine atony which has not responded to conventional methods of management. prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations. studies have shown that in such cases, the use of carboprost tromethamine injection has resulted in satisfactory control of hemorrhage, although it is unclear whether or not ongoing or delayed effects of previously administered ecbolic agents have contributed to the outcome. in a high proportion of cases, carboprost tromethamine injection used in this manner has resulted in the cessation of life threatening bleeding and the avoidance of emergency surgical intervention. 1.   hypersensitivity (including anaphylaxis and angioedema) to carboprost tromethamine injection [see adverse reactions, post-marketing experience ]. 2.   acute pelvic inflammatory disease. 3.   patients with active cardiac, pulmonary, renal or hepatic disease. warnings carboprost tromethamine, like other potent oxytocic agents, should be used only with strict adherence to recommended dosages. carboprost tromethamine should be used by medically trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities. carboprost tromethamine does not appear to directly affect the fetoplacental unit. therefore, the possibility does exist that the previable fetus aborted by carboprost tromethamine could exhibit transient life signs. carboprost tromethamine is not indicated if the fetus in utero has reached the stage of viability. carboprost tromethamine should not be considered a feticidal agent. evidence from animal studies has suggested that certain other prostaglandins have some teratogenic potential. although these studies do not indicate that carboprost tromethamine is teratogenic, any pregnancy termination with carboprost tromethamine that fails should be completed by some other means. this product contains benzyl alcohol. benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in premature infants.

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

amneal pharmaceuticals ny llc - doxepin hydrochloride (unii: 3u9a0fe9n5) (doxepin - unii:5asj6huz7d) - doxepin 10 mg - doxepin hcl capsules are recommended for the treatment of: - psychoneurotic patients with depression and/or anxiety. - depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol). - depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly). - psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. the target symptoms of psychoneurosis that respond particularly well to doxepin hcl capsules include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry. clinical experience has shown that doxepin hcl capsules is safe and well tolerated even in the elderly patient. owing to lack of clinical experience in the pediatric population, doxepin is not recommended for use in children under 12 years of age. doxepin is contraindicated in individuals who have shown hypersensitivity to the drug. possibility of cross sensitivity with other dibenzoxepines should be kept in mind. doxepin is contraindicated in patients with glaucoma or a tendency to urinary retention. these disorders should be ruled out, particularly in older patients.

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

amneal pharmaceuticals llc - phenazopyridine hydrochloride (unii: 0ewg668w17) (phenazopyridine - unii:k2j09emj52) - phenazopyridine hydrochloride 100 mg - pyridium is indicated for the symptomatic relief of pain, burning, urgency, frequency, and other discomforts arising from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or the passage of sounds or catheters. the use of phenazopyridine hcl for relief of symptoms should not delay definitive diagnosis and treatment of causative conditions. because it provides only symptomatic relief, prompt appropriate treatment of the cause of pain must be instituted and phenazopyridine hcl should be discontinued when symptoms are controlled. the analgesic action may reduce or eliminate the need for systemic analgesics or narcotics. it is, however, compatible with antibacterial therapy and can help to relieve pain and discomfort during the interval before antibacterial therapy controls the infection. treatment of a urinary tract infection with phenazopyridine hcl should not exceed two days because there is a lack of evidence that the combined administration of phenazopyridine hcl and an antibacterial provides greater benefit than administration of the antibacterial alone after two days. (see dosage and administration  section.) phenazopyridine hcl should not be used in patients who have previously exhibited hypersensitivity to it. the use of phenazopyridine hcl is contraindicated in patients with renal insufficiency.