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

micro labs limited - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - tramadol hydrochloride 37.5 mg - tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions ( 5.1)] , reserve tramadol hydrochloride and acetaminophen for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: - have not been tolerated or are not expected to be tolerated, - have not provided adequate analgesia or are not expected to provide adequate analgesia. tramadol hydrochloride and acetaminophen should not be used for an extended period of time. tramadol hydrochloride and acetaminophen is contraindicated for:   - all children younger than 12 years of age [see warnings and precautions ( 5.6)] - post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions ( 5.6)] . tramadol hydrochloride and acetaminophen is also contraindicated in patients with:   - significant respiratory depression [see warnings and precautions ( 5.2)] . - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.14)] . - patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.18)] . - previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see warnings and precautions ( 5.19)]. - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions ( 7)]. 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 tramadol hydrochloride and acetaminophen in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, the combination of tramadol and acetaminophen decreased fetal weights and increased supernumerary ribs at 1.6 times the maximum recommended human daily dosage (mrhd). in separate animal reproduction studies, tramadol administration alone during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd). tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the mrhd. reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen. treatment of pregnant rats with doses of acetaminophen approximately 1.3 times the maximum human daily dose (mrhd) showed evidence of fetotoxicity and increases in bone variations in the fetuses. in another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately 1.9 times the mhdd. in mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study. a reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in respiratory depression and 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 and signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions ( 5.4)] . neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during postmarketing. labor or delivery tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate. tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including tramadol hydrochloride and acetaminophen, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. tramadol has been shown to cross the placenta. the mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. the effect of tramadol hydrochloride and acetaminophen, if any, on the later growth, development, and functional maturation of the child is unknown. data animal data no drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and acetaminophen. the tramadol/acetaminophen combination product was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/434 mg/kg tramadol/acetaminophen (1.6 times the maximum daily human tramadol/acetaminophen dosage), but was not teratogenic at this dose level. embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs. tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. these doses on a mg/m 2 basis are 1.9, 0.8, and 4.9 times the maximum recommended human daily dosage (mrhd) for mouse, rat and rabbit, respectively. no drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. the dosages listed for mouse, rat and rabbit are 2.3, 2.6, and 19 times the mrhd, respectively. tramadol alone was evaluated in peri- and post-natal studies in rats. progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m 2 or 1.6 times the maximum daily human tramadol dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/m 2 or 2.6 times the maximum daily human tramadol dosage). studies in pregnant rats that received oral acetaminophen during organogenesis at doses up to 1.3 times the maximum human daily dose (mhdd = 2.6 grams/day, based on a body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose- related increase in bone variations (reduced ossification and rudimentary rib changes). offspring had no evidence of external, visceral, or skeletal malformations. when pregnant rats received oral acetaminophen throughout gestation at doses of 1.9-times the mhdd (based on a body surface area comparison), areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses. these effects did not occur in animals that received oral acetaminophen at doses 0.5-times the mhdd, based on a body surface area comparison. in a continuous breeding study, pregnant mice received 0.25, 0.5, or 1% acetaminophen via the diet (357, 715, or 1430 mg/kg/day). these doses are approximately 0.7, 1.3, and 2.7 times the mhdd, respectively, based on a body surface area comparison. a dose-related reduction in body weights of fourth and fifth litter offspring of the treated mating pair occurred during lactation and post-weaning at all doses. animals in the high dose group had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next generation pups. risk summary tramadol hydrochloride and acetaminophen is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. tramadol and its metabolite, o -desmethyl tramadol (m1), are present in human milk. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the m1 metabolite is more potent than tramadol in mu opioid receptor binding [see clinical pharmacology ( 12.1)]. published studies have reported tramadol and m1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of m1, potentially leading to higher levels of m1 in breast milk that can be dangerous in their breastfed infants. in women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with tramadol hydrochloride and acetaminophen. clinical considerations if infants are exposed to tramadol hydrochloride and acetaminophen through breast milk, they should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. data following a single iv 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of m1. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions ( 6.2), clinical pharmacology ( 12.2), nonclinical toxicology ( 13.1)] . the safety and effectiveness of tramadol hydrochloride and acetaminophen in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions ( 5.6)] . in some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. because of the risk of life-threatening respiratory depression and death: - tramadol hydrochloride and acetaminophen is contraindicated for all children younger than age 12 years of age [see contraindications ( 4)] . - tramadol hydrochloride and acetaminophen is contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see contraindications ( 4)] . - avoid the use of tramadol hydrochloride and acetaminophen in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. elderly patients (65 years of age or older) may have increased sensitivity to tramadol. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of tramadol hydrochloride and acetaminophen slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.2)]. tramadol and acetaminophen are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. the pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen in patients with impaired hepatic function have not been studied. based on information using tramadol immediate-release tablets in subjects with advanced cirrhosis of the liver, tramadol exposure was higher and half-lives of tramadol and active metabolite m1 were longer than in subjects with normal hepatic function [see clinical pharmacology ( 12.3)]. as tramadol and acetaminophen are both extensively metabolized by the liver, the use of tramadol hydrochloride and acetaminophen in patients with hepatic impairment is not recommended [see warnings and precautions ( 5.9)] . the pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen in patients with renal impairment has not been studied. based on studies using tramadol extended-release tablets, the excretion of tramadol and metabolite m1 is reduced in patients with creatinine clearance of less than 30 ml/min. in patients with creatinine clearances of less than 30 ml/min, it is recommended that the dosage of tramadol hydrochloride and acetaminophen not exceed 2 tablets every 12 hours. [see dosage and administration ( 2.3)] . the total amount of tramadol and m1 removed during a 4 hour dialysis period is less than 7% of the administered dose based on studies using tramadol alone. regularly evaluate closely for signs of respiratory depression, sedation, and hypotension. tramadol clearance was 20% higher in female subjects compared to males in four phase 1 studies of tramadol hydrochloride and acetaminophen in 50 male and 34 female healthy subjects. the clinical significance of this difference is unknown. tramadol hydrochloride and acetaminophen tablets contains tramadol, a schedule iv controlled substance. tramadol hydrochloride and acetaminophen tablets contains tramadol, a substance with potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions ( 5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of tramadol hydrochloride and acetaminophen 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 tramadol hydrochloride and acetaminophen 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 tramadol hydrochloride and acetaminophen tablets abuse include those with a history of prolonged use of any opioid including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride and acetaminophen tablets in combination with other abused drugs. “drug seeking” behavior is very common in persons with substance use disorders. drug seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. tramadol hydrochloride and acetaminophen, 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   tramadol hydrochloride and acetaminophen tablets abuse of tramadol hydrochloride and acetaminophen tablets poses a risk of overdose and death. the risk is increased with concurrent use of tramadol hydrochloride and acetaminophen tablets with alcohol and/or other cns depressants. tramadol hydrochloride and acetaminophen tablets is approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dosage 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 tramadol hydrochloride and acetaminophen tablets in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride and acetaminophen 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 tramadol hydrochloride and acetaminophen tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of the tramadol hydrochloride and acetaminophen 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), warnings and precautions ( 5.21)].   infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations ( 8.1)] .

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

stat rx usa llc - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline hydrochloride 25 mg - major depressive disorder – sertraline hydrochloride is indicated for the treatment of major depressive disorder in adults. the efficacy of sertraline hydrochloride in the treatment of a major depressive episode was established in six to eight week controlled trials of adult outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical trials under clinical pharmacology). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the antidepressant action of sertraline hydrochloride in hos

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

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

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

hikma pharmaceuticals usa inc. - methadone hydrochloride (unii: 229809935b) (methadone - unii:uc6vbe7v1z) - methadone hydrochloride 5 mg - methadone hydrochloride tablets are indicated for the: methadone hydrochloride tablets are contraindicated in patients with: risk summary: neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.5)] . pregnant women in methadone maintenance programs may have reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes and risk of continued or relapsing illicit opioid use. these risks should be considered in women treated with methadone hydrochloride tablets for maintenance treatment of opioid addiction. for women treated with methadone hydrochloride tablets for pain severe enough to require daily, around-the-clock, long-term opioid treatment, methadone hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the

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hikma pharmaceuticals usa inc. - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 4 mg - hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions (5.2)], reserve hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are contraindicated in patients with: risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)]. there are no available data with hydromorphone hydrochloride in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (hdd), respectively. in published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the hdd and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the hdd to pregnant mice. no malformations were noted at 4 or 40.5 times the hdd in pregnant rats or rabbits, respectively [see data]. based on animal data, advise pregnant women of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions : use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)]. labor or delivery : opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data : pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). there was no evidence of malformations or embryotoxicity reported. pregnant rabbits were treated with hydromorphone hydrochloride from gestation day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). there was no evidence of malformations or embryotoxicity reported. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on gestation day 8 to pregnant hamsters (6.4 to 87.2 times the hdd of 24 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. no neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day). in a published study, cf-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (gestation days 7 to 10). soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. the findings cannot be clearly attributed to maternal toxicity. increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from gestation day 7 to lactation day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the hdd of 24 mg based on body surface area, respectively). maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested. risk summary low levels of opioid analgesics have been detected in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets and any potential adverse effects on the breastfed infant from hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor infants exposed to hydromorphone hydrochloride through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of hydromorphone hydrochloride in pediatric patients have not been established. elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of hydromorphone hydrochloride slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)]. hydromorphone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. the pharmacokinetics of hydromorphone is affected by hepatic impairment. due to increased exposure of hydromorphone, patients with hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and regularly evaluated during dose titration. the pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. a further increase in cmax and auc of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see clinical pharmacology (12.3)]. the pharmacokinetics of hydromorphone is affected by renal impairment. in addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life. start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. patients with renal impairment should be regularly evaluated during dose titration [see clinical pharmacology (12.3)]. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a schedule ii controlled substance. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.2)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of hydromorphone hydrochloride increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of hydromorphone hydrochloride with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of hydromorphone hydrochloride abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use hydromorphone hydrochloride in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. hydromorphone hydrochloride, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of hydromorphone hydrochloride abuse of hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets poses a risk of overdose and death. the risk is increased with concurrent use of hydromorphone hydrochloride tablets with alcohol and/or other cns depressants. hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids. rapid tapering of hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration ( 2.7 ), warnings and precautions (5.14)]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations ( 8.1)] .

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hikma pharmaceuticals usa inc. - meperidine hydrochloride (unii: n8e7f7q170) (meperidine - unii:9e338qe28f) - meperidine hydrochloride 50 mg - meperidine hydrochloride tablets and oral solution are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions (5.2)] , reserve meperidine hydrochloride tablets and oral solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products] : meperidine hydrochloride tablets or oral solution should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. meperidine hydrochloride tablets or oral solution should not be used for the treatment of chronic pain. use of meperidine hydrochloride tablets or oral solution for an extended period of time may increase the risk of toxicity (e.g. seizures) from the accumulation of the meperidine metabolite, normeperidine . meperidine hydrochloride tablets and oral solution are contraindicated in patients with: risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)]. available data with meperidine is insufficient to inform a drug-associated risk for major birth defects and miscarriage. formal animal reproduction studies have not been conducted with meperidine. neural tube defects (exencephaly and cranioschisis) have been reported in hamsters administered a single bolus dose of meperidine during a critical period of organogenesis at 0.85 and 1.5 times the total human daily dose of 1,200 mg [see data]. adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions : use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)]. labor and delivery : opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. resuscitation may be required [see overdose (10)]. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. meperidine is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including meperidine, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data animal data : formal reproductive and developmental toxicology studies for meperidine have not been completed. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of meperidine hydrochloride (127 and 218 mg/kg, respectively) on gestation day 8 to pregnant hamsters (0.85 and 1.5 times the total daily dose of 1,200 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. risk summary meperidine appears in the milk of nursing mothers receiving the drug. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for meperidine and any potential adverse effects on the breastfed infant from meperidine hydrochloride tablets or oral solution or from the underlying maternal condition. clinical considerations monitor infants exposed to meperidine 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 [see adverse reactions (6), clinical pharmacology (12.2)], nonclinical toxicology (13.1)]. the safety and effectiveness of meperidine in pediatric patients has not been established. literature reports indicate that meperidine has a slower elimination rate in neonates and young infants compared to older children and adults. neonates and young infants may also be more susceptible to the effects, especially the respiratory depressant effects. if meperidine use is contemplated in neonates or young infants, any potential benefits of the drug need to be weighed against the relative risk of the patient. clinical studies of meperidine during product development did not include sufficient numbers of subjects aged 65 and over to evaluate age-related differences in safety or efficacy. literature reports indicate that geriatric patients have a slower elimination rate compared to young patients and they may be more susceptible to the effects of meperidine. reducing the total daily dose of meperidine is recommended in elderly patients, and the potential benefits of the drug should be weighed against the relative risk to a geriatric patient. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of meperidine hydrochloride tablets or oral solution slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.4, 5.11)]. meperidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. accumulation of meperidine and/or its active metabolite, normeperidine, can occur in patients with hepatic impairment. elevated serum levels have been reported to cause central nervous system excitatory effects. meperidine should therefore be used with caution in patients with hepatic impairment. titrate the dosage of meperidine hydrochloride tablets or oral solution slowly in patients with hepatic impairment and regularly evaluate for signs of central nervous system and respiratory depression. accumulation of meperidine and/or its active metabolite, normeperidine, can also occur in patients with renal impairment. meperidine should therefore be used with caution in patients with renal impairment. titrate the dosage of meperidine hydrochloride tablets or oral solution slowly in patients with renal impairment and regularly evaluate for signs of central nervous system and respiratory depression. meperidine hydrochloride tablets and oral solution contain meperidine, a schedule ii controlled substance. meperidine hydrochloride tablets and oral solution contain meperidine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.2)]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of meperidine hydrochloride tablets and oral solution 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 meperidine hydrochloride tablets and/or oral solution 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 meperidine hydrochloride tablets and oral solution abuse include those with a history of prolonged use of any opioid, including products containing meperidine, those with a history of drug or alcohol abuse, or those who use meperidine hydrochloride tablets and oral solution in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. meperidine hydrochloride tablets and oral solution, 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 meperidine hydrochloride tablets and oral solution abuse of meperidine hydrochloride tablets and oral solution poses a risk of overdose and death. the risk is increased with concurrent use of meperidine hydrochloride tablets and oral solution with alcohol and/or other cns depressants. meperidine hydrochloride tablets and oral solution are approved for oral use only. meperidine hydrochloride tablets have been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. inappropriate intravenous, intramuscular, or subcutaneous use of meperidine hydrochloride tablets and oral solution 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 meperidine hydrochloride tablets and oral solution in a patient physically dependent on opioids. rapid tapering of meperidine hydrochloride tablets and oral solution 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, gradually taper the dosage using a patient-specific plan that considers the following: the dose of meperidine hydrochloride tablets and oral solution 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 (2.6), and warnings and precautions (5.17)]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)].

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keltman pharmaceuticals inc. - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline hydrochloride 50 mg - major depressive disorder – sertraline hydrochloride is indicated for the treatment of major depressive disorder in adults. the efficacy of sertraline hydrochloride in the treatment of a major depressive episode was established in six to eight week controlled trials of adult outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical trials under clinical pharmacology). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the antidepressant action of sertraline hydrochloride in hos

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accord healthcare, inc. - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline 25 mg - sertraline hydrochloride tablets are indicated for the treatment of the following [see clinical studies (14)] : - major depressive disorder (mdd) - obsessive-compulsive disorder (ocd) - panic disorder (pd) - posttraumatic stress disorder (ptsd) - social anxiety disorder (sad) - premenstrual dysphoric disorder (pmdd) sertraline hydrochloride tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois, (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)] . - taking pimozide [see drug interactions (7.1)] . - with known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [see adverse reactions (6.1, 6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers should encourage patients to enroll by calling the national pregnancy registry for antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.3) and clinical considerations]. overall, available published epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. some studies have reported increases for specific major birth defects; however, these study results are inconclusive [see data] . there are clinical considerations regarding neonates exposed to ssris and snris, including sertraline hydrochloride, during the third trimester of pregnancy [see clinical considerations]. although no teratogenicity was observed in animal reproduction studies, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (mrhd) in rats and doses 3.1 times the mrhd in rabbits on a mg/m 2 basis in adolescents. when sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first four days after birth at the mrhd [see data] . the background risk of major birth defects and miscarriage for the indicated population are unknown. 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. advise a pregnant woman of possible risks to the fetus when prescribing sertraline hydrochloride tablets. clinical considerations disease-associated maternal and/or embryo/fetal risk a prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of sertraline hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.3)]. fetal/neonatal adverse reactions exposure to ssris and snris, including sertraline hydrochloride in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (pphn). when treating a pregnant woman with sertraline hydrochloride during the third trimester, carefully consider both the potential risks and benefits of treatment. monitor neonates who were exposed to sertraline hydrochloride in the third trimester of pregnancy for pphn and drug discontinuation syndrome [see data]. data human data third trimester exposure neonates exposed to sertraline hydrochloride and other ssris or snris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. these findings are based on post-marketing reports. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. in some cases, the clinical picture was consistent with serotonin syndrome [see warnings and precautions (5.2)] . exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. in a retrospective case-control study of 377 women whose infants were born with pphn and 836 women whose infants were born healthy, the risk for developing pphn was approximately six-fold higher for infants exposed to ssris after the 20 th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. a study of 831,324 infants born in sweden in 1997 to 2005 found a pphn risk ratio of 2.4 (95% ci 1.2 to 4.3) associated with patient-reported maternal use of ssris “in early pregnancy” and a pphn risk ratio of 3.6 (95% ci 1.2 to 8.3) associated with a combination of patient-reported maternal use of ssris “in early pregnancy” and an antenatal ssri prescription “in later pregnancy”. first trimester exposure the weight of evidence from epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in pregnant women who were not exposed to sertraline. a meta-analysis of studies suggest no increase in the risk of total malformations (summary odds ratio=1.01, 95% ci=0.88 to 1.17) or cardiac malformations (summary odds ratio=0.93, 95% ci=0.70 to 1.23) among offspring of women with first trimester exposure to sertraline. an increased risk of congenital cardiac defects, specifically septal defects, the most common type of congenital heart defect, was observed in some published epidemiologic studies with first trimester sertraline exposure; however, most of these studies were limited by the use of comparison populations that did not allow for the control of confounders such as the underlying depression and associated conditions and behaviors, which may be factors associated with increased risk of these malformations. animal data reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and  40 mg/kg/day, respectively. these doses correspond to approximately 3.1 times the maximum recommended human dose (mrhd) of 200 mg/day on a mg/m 2 basis in adolescents. there was no evidence of teratogenicity at any dose level. when pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0.4 times the mrhd on a mg/m 2 basis) in rats and 40 mg/kg (3.1 times the mrhd on a mg/m 2 basis) in rabbits. when female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth. pup body weights were also decreased during the first four days after birth. these effects occurred at a dose of 20 mg/kg (0.8 times the mrhd on a mg/m 2 basis). the no effect dose for rat pup mortality was 10 mg/kg (0.4 times the mrhd on a mg/m 2 basis). the decrease in pup survival was shown to be due to in utero exposure to sertraline. the clinical significance of these effects is unknown. risk summary available data from published literature demonstrate low levels of sertraline and its metabolites in human milk [see data] . there are no data on the effects of sertraline on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sertraline hydrochloride and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. data in a published pooled analysis of 53 mother-infant pairs, exclusively human milk-fed infants had an average of 2% (range 0% to 15%) of the sertraline serum levels measured in their mothers. no adverse reactions were observed in these infants. the safety and efficacy of sertraline hydrochloride have been established in the treatment of ocd in pediatric patients aged 6 to 17 [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . safety and effectiveness in pediatric patients in patients with ocd below the age of 6 have not been established. safety and effectiveness have not been established in pediatric patients for indications other than ocd. two placebo-controlled trials were conducted in pediatric patients with mdd, but the data were not sufficient to support an indication for use in pediatric patients. monitoring pediatric patients treated with sertraline hydrochloride monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dose increases or decreases [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed with the use of ssris. monitor weight and growth in pediatric patients treated with an ssri such as sertraline hydrochloride . weight loss in studies in pediatric patients with mdd in a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50 mg to 200 mg) outpatient trials for mdd (n=373), there was a difference in weight change between sertraline hydrochloride and placebo of roughly 1 kg, for both children (ages 6 to 11) and adolescents (ages 12 to 17), in both age groups representing a slight weight loss for the sertraline hydrochloride group compared to a slight gain for the placebo group. for children, about 7% of the sertraline hydrochloride-treated patients had a weight loss greater than 7% of body weight compared to 0% of the placebo-treated patients; for adolescents, about 2% of sertraline hydrochloride-treated patients had a weight loss > 7% of body weight compared to about 1% of placebo-treated patients. a subset of patients who completed the randomized controlled trials in patients with mdd (sertraline hydrochloride n=99, placebo n=122) were continued into a 24-week, flexible-dose, open-label, extension study. those subjects who completed 34 weeks of sertraline hydrochloride treatment (10 weeks in a placebo-controlled trial + 24 weeks open-label, n=68) had weight gain that was similar to that expected using data from age-adjusted peers. however, there are no studies that directly evaluate the long-term effects of sertraline hydrochloride on the growth, development, and maturation in pediatric patients. juvenile animal data a study conducted in juvenile rats at clinically relevant doses showed delay in sexual maturation, but there was no effect on fertility in either males or females. in this study in which juvenile rats were treated with oral doses of sertraline at 0, 10, 40 or 80 mg/kg/day from postnatal day 21 to 56, a delay in sexual maturation was observed in males treated with 80 mg/kg/day and females treated with doses ≥10 mg/kg/day. there was no effect on male and female reproductive endpoints or neurobehavioral development up to the highest dose tested (80 mg/kg/day), except a decrease in auditory startle response in females at 40 and 80 mg/kg/day at the end of treatment but not at the end of the drug-free period. the highest dose of 80 mg/kg/day produced plasma levels (auc) of sertraline 5 times those seen in pediatric patients (6 to 17 years of age) receiving the maximum recommended dose of sertraline (200 mg/day). of the total number of patients in clinical studies of sertraline hydrochloride in patients with mdd, ocd, pd, ptsd, sad and pmdd, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. in 354 geriatric subjects treated with sertraline hydrochloride in mdd placebo-controlled trials, the overall profile of adverse reactions was generally similar to that shown in table 3  [see adverse reactions (6.1)], except for tinnitus, arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients. snris and ssris, including sertraline hydrochloride, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.8) ] . the recommended dosage in patients with mild hepatic impairment (child-pugh score 5 or 6) is half the recommended dosage due to increased exposure in this patient population. the use of sertraline hydrochloride in patients with moderate (child-pugh score 7 to 10) or severe hepatic impairment (child-pugh score 10 to 15) is not recommended, because sertraline hydrochloride is extensively metabolized, and the effects of sertraline hydrochloride in patients with moderate and severe hepatic impairment have not been studied [see dosage and administration (2.4), clinical pharmacology (12.3)] . no dose adjustment is needed in patients with mild to severe renal impairment. sertraline exposure does not appear to be affected by renal impairment [see clinical pharmacology (12.3)] . sertraline hydrochloride tablets contain sertraline, which is not a controlled substance. in a placebo-controlled, double-blind, randomized study of the comparative abuse liability of sertraline hydrochloride, alprazolam, and d-amphetamine in humans, sertraline hydrochloride did not produce the positive subjective effects indicative of abuse potential, such as euphoria or drug liking, that were observed with the other two drugs.

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

rising pharma holdings, inc. - sertraline hydrochloride (unii: uti8907y6x) (sertraline - unii:quc7nx6wmb) - sertraline 20 mg in 1 ml - sertraline hydrochloride oral solution is indicated for the treatment of the following [see clinical studies (14)] : - major depressive disorder (mdd) - obsessive-compulsive disorder (ocd) - panic disorder (pd) - posttraumatic stress disorder (ptsd) - social anxiety disorder (sad) - premenstrual dysphoric disorder (pmdd) sertraline hydrochloride oral solution is contraindicated in patients: - taking, or within 14 days of stopping, maois, (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)] . - taking pimozide [see drug interactions (7.1)] . - with known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [see adverse reactions (6.1, 6.2)]. in addition to the contraindications for all sertraline hydrochloride oral solution formulations listed above, sertraline hydrochloride oral solution is contraindicated in patients: - taking disulfiram. sertraline hydrochloride oral solution contains alcohol, and concomitant use of sertraline hydrochloride oral solution and disulfiram may result in a disulfiram-alcohol reaction. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers should encourage patients to enroll by calling the national pregnancy registry for antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum  hemorrhage [see warnings and precautions (5.3) and clinical considerations] . overall, available published epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. some studies have reported increases for specific major birth defects; however, these study results are inconclusive [see data] . there are clinical considerations regarding neonates exposed to ssris and snris, including sertraline hydrochloride, during the third trimester of pregnancy [see clinical considerations]. although no teratogenicity was observed in animal reproduction studies, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (mrhd) in rats and doses 3.1 times the mrhd in rabbits on a mg/m2 basis in adolescents. when sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first four days after birth at the mrhd [see data] . the background risk of major birth defects and miscarriage for the indicated population are unknown. 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. advise a pregnant woman of possible risks to the fetus when prescribing sertraline hydrochloride. sertraline hydrochloride oral solution contains 12% alcohol and is not recommended during pregnancy because there is no known safe level of alcohol exposure during pregnancy. clinical considerations disease-associated maternal and/or embryo/fetal risk a prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of sertraline hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.3)] . fetal/neonatal adverse reactions exposure to ssris and snris, including sertraline hydrochloride in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (pphn). when treating a pregnant woman with sertraline hydrochloride during the third trimester, carefully consider both the potential risks and benefits of treatment. monitor neonates who were exposed to sertraline hydrochloride in the third trimester of pregnancy for pphn and drug discontinuation syndrome [see data]. data human data third trimester exposure neonates exposed to sertraline hydrochloride and other ssris or snris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. these findings are based on post-marketing reports. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. in some cases, the clinical picture was consistent with serotonin syndrome [see warnings and precautions (5.2)] . exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. in a retrospective case-control study of 377 women whose infants were born with pphn and 836 women whose infants were born healthy, the risk for developing pphn was approximately six-fold higher for infants exposed to ssris after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. a study of 831,324 infants born in sweden in 1997 to 2005 found a pphn risk ratio of 2.4 (95% ci 1.2-4.3) associated with patient-reported maternal use of ssris “in early pregnancy” and a pphn risk ratio of 3.6 (95% ci 1.2 to 8.3) associated with a combination of patient-reported maternal use of ssris “in early pregnancy” and an antenatal ssri prescription “in later pregnancy”. first trimester exposure the weight of evidence from epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in pregnant women who were not exposed to sertraline. a meta-analysis of studies suggest no increase in the risk of total malformations (summary odds ratio=1.01, 95% ci=0.88 to 1.17) or cardiac malformations (summary odds ratio=0.93, 95% ci=0.70 to 1.23) among offspring of women with first trimester exposure to sertraline. an increased risk of congenital cardiac defects, specifically septal defects, the most common type of congenital heart defect, was observed in some published epidemiologic studies with first trimester sertraline exposure; however, most of these studies were limited by the use of comparison populations that did not allow for the control of confounders such as the underlying depression and associated conditions and behaviors, which may be factors associated with increased risk of these malformations. animal data reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and  40 mg/kg/day, respectively. these doses correspond to approximately 3.1 times the maximum recommended human dose (mrhd) of 200 mg/day on a mg/m2 basis in adolescents. there was no evidence of teratogenicity at any dose level. when pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0.4 times the mrhd on a mg/m2 basis) in rats and 40 mg/kg (3.1 times the mrhd on a mg/m2 basis) in rabbits. when female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth. pup body weights were also decreased during the first four days after birth. these effects occurred at a dose of 20 mg/kg (0.8 times the mrhd on a mg/m2 basis). the no effect dose for rat pup mortality was 10 mg/kg (0.4 times the mrhd on a mg/m2 basis). the decrease in pup survival was shown to be due to in utero exposure to sertraline. the clinical significance of these effects is unknown. risk summary available data from published literature demonstrate low levels of sertraline and its metabolites in human milk [see data] . there are no data on the effects of sertraline on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sertraline hydrochloride and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. data in a published pooled analysis of 53 mother-infant pairs, exclusively human milk-fed infants had an average of 2% (range 0% to 15%) of the sertraline serum levels measured in their mothers. no adverse reactions were observed in these infants. the safety and efficacy of sertraline hydrochloride have been established in the treatment of ocd in pediatric patients aged 6 to 17 [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . safety and effectiveness in pediatric patients in patients with ocd below the age of 6 have not been established. safety and effectiveness have not been established in pediatric patients for indications other than ocd. two placebo-controlled trials were conducted in pediatric patients with mdd, but the data were not sufficient to support an indication for use in pediatric patients. monitoring pediatric patients treated with sertraline hydrochloride monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dose increases or decreases [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed with the use of ssris. monitor weight and growth in pediatric patients treated with an ssri such as sertraline hydrochloride. weight loss in studies in pediatric patients with mdd in a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50 to 200 mg) outpatient trials for mdd (n=373), there was a difference in weight change between sertraline hydrochloride and placebo of roughly 1 kg, for both children (ages 6 to 11) and adolescents (ages 12 to 17), in both age groups representing a slight weight loss for the sertraline hydrochloride group compared to a slight gain for the placebo group. for children, about 7% of the sertraline hydrochloride-treated patients had a weight loss greater than 7% of body weight compared to 0% of the placebo-treated patients; for adolescents, about 2% of sertraline hydrochloride-treated patients had a weight loss > 7% of body weight compared to about 1% of placebo-treated patients. a subset of patients who completed the randomized controlled trials in patients with mdd (sertraline hydrochloride n=99, placebo n=122) were continued into a 24-week, flexible-dose, open-label, extension study. those subjects who completed 34 weeks of sertraline hydrochloride treatment (10 weeks in a placebo-controlled trial + 24 weeks open-label, n=68) had weight gain that was similar to that expected using data from age-adjusted peers. however, there are no studies that directly evaluate the long-term effects of sertraline hydrochloride on the growth, development, and maturation in pediatric patients. alcohol content in sertraline hydrochloride oral solution sertraline hydrochloride oral solution contains 12% alcohol. juvenile animal data a study conducted in juvenile rats at clinically relevant doses showed delay in sexual maturation, but there was no effect on fertility in either males or females. in this study in which juvenile rats were treated with oral doses of sertraline at 0, 10, 40 or 80 mg/kg/day from postnatal day 21 to 56, a delay in sexual maturation was observed in males treated with 80 mg/kg/day and females treated with doses ≥10 mg/kg/day. there was no effect on male and female reproductive endpoints or neurobehavioral development up to the highest dose tested (80 mg/kg/day), except a decrease in auditory startle response in females at 40 and 80 mg/kg/day at the end of treatment but not at the end of the drug–free period. the highest dose of 80 mg/kg/day produced plasma levels (auc) of sertraline 5 times those seen in pediatric patients (6 to 17 years of age) receiving the maximum recommended dose of sertraline (200 mg/day). of the total number of patients in clinical studies of sertraline hydrochloride in patients with mdd, ocd, pd, ptsd, sad and pmdd, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. in 354 geriatric subjects treated with sertraline hydrochloride in mdd placebo-controlled trials, the overall profile of adverse reactions was generally similar to that shown in table 3 [see adverse reactions (6.1)], except for tinnitus, arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients. snris and ssris, including sertraline hydrochloride, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.8) ] . the recommended dosage in patients with mild hepatic impairment (child-pugh score 5 or 6) is half the recommended dosage due to increased exposure in this patient population. the use of sertraline hydrochloride in patients with moderate (child-pugh score 7 to 10) or severe hepatic impairment (child-pugh score 10 to 15) is not recommended, because sertraline hydrochloride is extensively metabolized, and the effects of sertraline hydrochloride in patients with moderate and severe hepatic impairment have not been studied [see dosage and administration (2.4), clinical pharmacology (12.3)] . no dose adjustment is needed in patients with mild to severe renal impairment. sertraline exposure does not appear to be affected by renal impairment [see clinical pharmacology (12.3)] . sertraline hydrochloride oral solution contains sertraline, which is not a controlled substance. in a placebo-controlled, double-blind, randomized study of the comparative abuse liability of sertraline hydrochloride oral solution, alprazolam, and d-amphetamine in humans, sertraline hydrochloride oral solution did not produce the positive subjective effects indicative of abuse potential, such as euphoria or drug liking, that were observed with the other two drugs.

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

aurolife pharma, llc - oxymorphone hydrochloride (unii: 5y2ei94nbc) (oxymorphone - unii:9vxa968e0c) - oxymorphone hydrochloride 5 mg - oxymorphone hydrochloride tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve oxymorphone hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia oxymorphone hydrochloride tablets are contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see w