Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - lurasidone hydrochloride (unii: o0p4i5851i) (lurasidone - unii:22ic88528t) - lurasidone hydrochloride tablets are indicated for: - monotherapy treatment of adult and pediatric patients (10 to 17 years) with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - adjunctive treatment with lithium or valproate in adult patients with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - known hypersensitivity to lurasidone hydrochloride or any components in the formulation. angioedema has been observed with lurasidone [see adverse reactions (6.1)] . - strong cyp3a4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see drug interactions (7.1)] . - strong cyp3a4 inducers (e.g., rifampin, avasimibe, st. john’s wort, phenytoin, carbamazepine, etc.) [see drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lurasidone hydrochloride during pregnancy. for more information, contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery [see clinical considerations] . there are no studies of lurasidone hydrochloride use in pregnant women. the limited available data are not sufficient to inform a drug-associated risk of birth defects or miscarriage. in animal reproduction studies, no teratogenic effects were seen in pregnant rats and rabbits given lurasidone during the period of organogenesis at doses approximately 1.5- and 6-times, the maximum recommended human dose (mrhd) of 160 mg/day, respectively based on mg/m2 body surface area [see data] . the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth 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 extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. these symptoms have varied in severity. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. data animal data pregnant rats were treated with oral lurasidone at doses of 3, 10, and 25 mg/kg/day during the period of organogenesis. these doses are 0.2, 0.6, and 1.5 times the mrhd of 160 mg/day based on mg/m2 body surface area. no teratogenic or embryo-fetal effects were observed up to 1.5 times the mrhd of 160 mg/day, based on mg/m2 . pregnant rabbits were treated with oral lurasidone at doses of 2, 10, and 50 mg/kg/day during the period of organogenesis. these doses are 0.2, 1.2 and 6 times the mrhd of 160 mg/day based on mg/m2 . no teratogenic or embryo-fetal effects were observed up to 6 times the mrhd of 160 mg/day based on mg/m2 . pregnant rats were treated with oral lurasidone at doses of 0.4, 2, and 10 mg/kg/day during the periods of organogenesis and lactation. these doses are 0.02, 0.1 and 0.6 times the mrhd of 160 mg/day based on mg/m2 . no pre- and postnatal developmental effects were observed up to 0.6 times the mrhd of 160 mg/day, based on mg/m2 . risk summary lactation studies have not been conducted to assess the presence of lurasidone in human milk, the effects on the breastfed infant, or the effects on milk production. lurasidone is present in rat milk. the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for lurasidone hydrochloride and any potential adverse effects on the breastfed infant from lurasidone hydrochloride or from the underlying maternal condition. bipolar depression the safety and effectiveness of lurasidone hydrochloride tablet 20 to 80 mg/day for the treatment of bipolar depression in pediatric patients (10 to 17 years) was established in a 6-week, placebo-controlled clinical study in 347 pediatric patients [see dosage and administration (2.2), adverse reactions (6.1), and clinical studies (14.2)]. the safety and effectiveness of lurasidone hydrochloride has not been established in pediatric patients less than 10 years of age with bipolar depression. irritability associ ated with autistic disorder the effectiveness of lurasidone hydrochloride in pediatric patients for the treatment of irritability associated with autistic disorder has not been established. efficacy was not demonstrated in a 6-week study evaluating lurasidone hydrochloride 20 mg/day and 60 mg/day for the treatment of pediatric patients 6 to 17 years of age with irritability associated with autistic disorder diagnosed by diagnostic and statistical manual of mental disorders, 4th ed., text revision [dsm-iv-tr] criteria. the primary objective of the study as measured by improvement from baseline in the irritability subscale of the aberrant behavior checklist (abc) at endpoint (week 6) was not met. a total of 149 patients were randomized to lurasidone hydrochloride or placebo. vomiting occurred at a higher rate than reported in other lurasidone hydrochloride studies (4/49 or 8% for 20 mg, 14/51 or 27% for 60 mg, and 2/49 or 4% for placebo), particularly in children ages 6 to 12 (13 out of 18 patients on lurasidone hydrochloride with vomiting). in a long-term, open-label study that enrolled pediatric patients (age 6 to 17 years) with bipolar depression, autistic disorder or another indication, from three short-term, placebo-controlled trials, 54% (378/701) received lurasidone for 104 weeks. there was one adverse event in this trial that was considered possibly drug-related and has not been reported in adults receiving lurasidone: a 10 year old male experienced a prolonged, painful erection, consistent with priapism, that led to treatment discontinuation. in this trial, the mean increase in height from open-label baseline to week 104 was 4.94 cm. to adjust for normal growth, z-scores were derived (measured in standard deviations [sd]), which normalize for the natural growth of children and adolescents by comparisons to age- and sex-matched population standards. a z-score change < 0.5 sd is considered not clinically significant. in this trial, the mean change in height z-score from open-label baseline to week 104 was +0.05 sd, indicating minimal deviation from the normal growth curve. juvenile animal studies adverse effects were seen on growth, physical and neurobehavioral development at doses as low as 0.2 times the mrhd based on mg/m2 . lurasidone was orally administered to rats from postnatal days 21 through 91 (this period corresponds to childhood, adolescence, and young adulthood in humans) at doses of 3, 30, and 150 (males) or 300 (females) mg/kg/day which are 0.2 to 10 times (males) and 20 times (females) the maximum recommended adult human dose (mrhd) of 160 mg/day based on mg/m2 . the adverse effects included dose-dependent decreases in femoral length, bone mineral content, body and brain weights at 2 times the mrhd in both sexes, and motor hyperactivity at 0.2 and 2 times the mrhd in both sexes based on mg/m2 . in females, there was a delay in attainment of sexual maturity at 2 times the mrhd, associated with decreased serum estradiol. mortality occurred in both sexes during early post-weaning period and some of the male weanlings died after only 4 treatments at doses as low as 2 times the mrhd based on mg/m2 . histopathological findings included increased colloid in the thyroids and inflammation of the prostate in males at 10 times mrhd based on mg/m2 and mammary gland hyperplasia, increased vaginal mucification, and increased ovarian atretic follicles at doses as low as 0.2 times the mrhd based on mg/m2 . some of these findings were attributed to transiently elevated serum prolactin which was seen in both sexes at all doses. however, there were no changes at any dose level in reproductive parameters (fertility, conception indices, spermatogenesis, estrous cycle, gestation length, parturition, number of pups born). the no effect dose for neurobehavioral changes in males is 0.2 times the mrhd based on mg/m2 and could not be determined in females. the no effect dose for growth and physical development in both sexes is 0.2 times the mrhd based on mg/m2 . clinical studies with lurasidone hydrochloride did not include sufficient numbers of patients aged 65 and older to determine whether or not they respond differently from younger patients. in elderly patients with psychosis (65 to 85), lurasidone hydrochloride concentrations (20 mg/day) were similar to those in young subjects. it is unknown whether dose adjustment is necessary on the basis of age alone. elderly patients with dementia-related psychosis treated with lurasidone hydrochloride are at an increased risk of death compared to placebo. lurasidone hydrochloride is not approved for the treatment of patients with dementia-related psychosis [see boxed warning, warnings and precautions (5.1, 5.3)] . reduce the maximum recommended dosage in patients with moderate or severe renal impairment (clcr < 50 ml/minute). patients with impaired renal function (clcr < 50 ml/minute) had higher exposure to lurasidone than patients with normal renal function [see clinical pharmacology (12.3)] . greater exposure may increase the risk of lurasidone hydrochloride-associated adverse reactions [see dosage and administration (2.4)] . reduce the maximum recommended dosage in patients with moderate to severe hepatic impairment (child-pugh score ≥ 7). patients with moderate to severe hepatic impairment (child- pugh score ≥ 7) generally had higher exposure to lurasidone than patients with normal hepatic function [see clinical pharmacology (12.3)] . greater exposure may increase the risk of lurasidone hydrochloride-associated adverse reactions [see dosage and administration (2.5)] . no dosage adjustment for lurasidone hydrochloride is required on the basis of a patient’s sex, race, or smoking status [see clinical pharmacology (12.3)]. lurasidone hydrochloride is not a controlled substance. lurasidone hydrochloride has not been systematically studied in humans for its potential for abuse or physical dependence or its ability to induce tolerance. while clinical studies with lurasidone hydrochloride did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict the extent to which a cns-active drug will be misused, diverted and/or abused once it is marketed. patients should be evaluated carefully for a history of drug abuse, and such patients should be observed carefully for signs of lurasidone hydrochloride misuse or abuse (e.g., development of tolerance, drug-seeking behavior, increases in dose).

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals of new york llc - lacosamide (unii: 563ks2pqy5) (lacosamide - unii:563ks2pqy5) - lacosamide tablets are indicated for the treatment of partial-onset seizures in patients 4 years of age and older. additional pediatric use information is approved for ucb, inc.’s vimpat® (lacosamide) tablets. however, due to ucb, inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. none.  pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as lacosamide, during pregnancy. encourage women who are taking lacosamide during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary available data from the north american antiepileptic drug (naaed) pregnancy registry, a prospective cohort study, case reports, and a case series with lacosamide use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriag

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - salsalate (unii: v9mo595c9i) (salsalate - unii:v9mo595c9i) - salsalate 500 mg - carefully consider the potential benefits and risks of salsalate tablets and other treatment options before deciding to use salsalate tablets. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder. salsalate tablets are contraindicated in patients with known hypersensitivity to salsalate. salsalate tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings – anaphylactoid reactions , and precautions - preexisting asthma ). salsalate tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (cabg) surgery (see warnings ). drug abuse and dependence have not been reported with salsalate.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1), misoprostol (unii: 0e43v0bb57) (misoprostol - unii:0e43v0bb57) - diclofenac sodium 50 mg - diclofenac sodium and misoprostol delayed-release tablets are indicated for treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in adult patients at high risk of developing nsaid-induced gastric and duodenal ulcers and their complications. for a list of factors that may increase the risk of nsaid-induced gastric and duodenal ulcers and their complications [see warnings and precautions (5.3)] . diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the following patients: - pregnancy. use of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, during pregnancy can result in maternal and fetal harm, including uterine rupture, abortion, premature birth, or birth defects [see warnings and precautions (5.1)  and use in specific populations (8.1)] . - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.2)] . - active gastrointestinal bleeding [see warnings and precautions (5.3)] . - histo

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - montelukast sodium (unii: u1o3j18sfl) (montelukast - unii:mhm278sd3e) - montelukast 10 mg - montelukast sodium tablets are indicated for the prophylaxis and chronic treatment of asthma in adults and adolescents 15 years of age and older. montelukast sodium tablets are indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 15 years of age and older. montelukast sodium tablets are indicated for the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older and perennial allergic rhinitis in patients 15 years of age and older. because the benefits of montelukast sodium tablets may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions (5.1)] , reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium tablets are not indicated for the treatment of an acute asthma attack. montelukast sodium tablets are contraindicated in patients with hypersensitivity to any of its components. risk summary available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see data] . in animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (mrhdod) based on aucs [see data]. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age. human data published data from prospective and retrospective cohort studies have not identified an association with montelukast sodium use during pregnancy and major birth defects. available studies have methodologic limitations, including small sample size, in some cases retrospective data collection, and inconsistent comparator groups. animal data in embryo-fetal development studies, montelukast administered to pregnant rats and rabbits during organogenesis (gestation days 6 to 17 in rats and 6 to 18 in rabbits) did not cause any adverse developmental effects at maternal oral doses up to 400 and 300 mg/kg/day in rats and rabbits, respectively (approximately 100 and 110 times the auc in humans at the mrhdod, respectively). risk summary a published clinical lactation study reports the presence of montelukast in human milk. data available on the effects of the drug on infants, either directly [see use in specific populations (8.4)]  or through breast milk, do not suggest a significant risk of adverse reactions from exposure to montelukast sodium. the effects of the drug on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for montelukast sodium and any potential adverse reactions on the breastfed infant from montelukast sodium or from the underlying maternal condition. the safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established. of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age 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. the pharmacokinetic profile and the oral bioavailability of a single 10 mg oral dose of montelukast are similar in elderly and younger adults. the plasma half-life of montelukast is slightly longer in the elderly. no dosage adjustment in the elderly is required. no dosage adjustment is recommended in patients with mild-to-moderate hepatic insufficiency [see clinical pharmacology (12.3)] . no dosage adjustment is recommended in patients with renal insufficiency [see clinical pharmacology (12.3) ] .

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - colchicine (unii: sml2y3j35t) (colchicine - unii:sml2y3j35t) - colchicine 0.6 mg - colchicine tablets, usp are indicated for prophylaxis and the treatment of acute gout flares. - prophylaxis of gout flares: colchicine tablets, usp are indicated for prophylaxis of gout flares. - treatment of gout flares: colchicine tablets, usp are indicated for treatment of acute gout flares when taken at the first sign of a flare. colchicine tablets, usp are indicated in adults and children four years or older for treatment of familial mediterranean fever (fmf). patients with renal or hepatic impairment should not be given colchicine, usp in conjunction with p-gp or strong cyp3a4 inhibitors (this includes all protease inhibitors except fosamprenavir). in these patients, life-threatening and fatal colchicine, usp toxicity has been reported with colchicine, usp taken in therapeutic doses. risk summary available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal ou

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 5 mg - oxycodone hydrochloride (hcl) 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, even at recommended doses [see warnings and precautions (5.1)] , reserve oxycodone hcl tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): - have not been tolerated or are not expected to be tolerated, - have not provided adequate analgesia or are not expected to provide adequate analgesia. oxycodone hcl is 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 or hypercarbia [see warnings and precautions (5.7)]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.11)] . - known hypersensitivity (e.g., anaphylaxis) to oxycodone [see adverse reactions (6.2)] . risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with oxycodone hcl in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. 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 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 prolonged use of opioid analgesics during pregnancy for medical or non-medical 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 hcl is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including oxycodone hcl, 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 hcl, 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 hcl and any potential adverse effects on the breastfed infant from oxycodone hcl or from the underlying maternal condition. clinical considerations infants exposed to oxycodone hcl through breast milk 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 breastfeeding is stopped. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2)] . the safety and efficacy of oxycodone hcl in pediatric patients have not been evaluated. of the total number of subjects in clinical studies of oxycodone hcl, 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 hcl slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.7)] . oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 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 hcl and titrate carefully. monitor closely 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 hcl and titrate carefully. monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)] . oxycodone hcl tablets contains oxycodone, a schedule ii controlled substance. oxycodone hcl tablets contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. oxycodone hcl can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)] . all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. oxycodone hcl, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of  oxycodone hcl oxycodone hcl tablets are for oral use only. abuse of oxycodone hcl poses a risk of overdose and death. the risk is increased with concurrent abuse of oxycodone hcl with alcohol and other central nervous system depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue oxycodone hcl in a patient physically dependent on opioids. rapid tapering of oxycodone hcl in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing oxycodone hcl, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone hcl the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.4), warnings and precautions (5.13) ] . 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)] .

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals of new york llc - gabapentin (unii: 6cw7f3g59x) (gabapentin - unii:6cw7f3g59x) - gabapentin 100 mg - gabapentin capsules are indicated for: - management of postherpetic neuralgia in adults - adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy gabapentin capsules are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as gabapentin, during pregnancy. encourage women who are taking gabapentin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. in nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically [see data]. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 % to 4% and 15% to 20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data when pregnant mice received oral doses of gabapentin (500 mg, 1,000 mg, or 3,000 mg/kg/day) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. the no-effect dose for embryofetal developmental toxicity in mice (500 mg/kg/day) is less than the maximum recommended human dose (mrhd) of 3,600 mg on a body surface area (mg/m2 ) basis. in studies in which rats received oral doses of gabapentin (500 mg to 2,000 mg/kg/day) during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. the lowest dose tested is similar to the mrhd on a mg/m2 basis. when pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60 mg, 300 mg, or 1,500 mg/kg). the lowest dose tested is less than the mrhd on a mg/m2 basis. in a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. the clinical significance of these findings is unknown. risk summary gabapentin is secreted in human milk following oral administration. the effects on the breastfed infant and on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gabapentin and any potential adverse effects on the breastfed infant from gabapentin or from the underlying maternal condition. safety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established. safety and effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established [see clinical studies (14.2)]. the total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older. there was a larger treatment effect in patients 75 years of age and older compared to younger patients who received the same dosage. since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients ≥ 75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function. however, other factors cannot be excluded. the types and incidence of adverse reactions were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age. clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. 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 cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients [see dosage and administration (2.4), adverse reactions (6), and clinical pharmacology (12.3)]. dosage adjustment in adult patients with compromised renal function is necessary [see dosage and administration (2.3)  and clinical pharmacology (12.3)]. pediatric patients with renal insufficiency have not been studied. dosage adjustment in patients undergoing hemodialysis is necessary [see dosage and administration (2.3)  and clinical pharmacology (12.3)]. gabapentin is not a scheduled drug. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. gabapentin does not exhibit affinity for benzodiazepine, opioid (mu, delta or kappa), or cannabinoid 1 receptor sites. gabapentin misuse and abuse have been reported in the postmarketing setting and published literature. most of the individuals described in these reports had a history of polysubstance abuse. some of these individuals were taking higher than recommended doses of gabapentin for unapproved uses. when prescribing gabapentin carefully evaluate patients for a history of drug abuse and observe them for signs and symptoms of gabapentin misuse or abuse (e.g., self-dose escalation and drug-seeking behavior). the abuse potential of gabapentin has not been evaluated in human studies. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. there are rare postmarketing reports of individuals experiencing withdrawal symptoms shortly after discontinuing higher than recommended doses of gabapentin used to treat illnesses for which the drug is not approved. such symptoms included agitation, disorientation and confusion after suddenly discontinuing gabapentin that resolved after restarting gabapentin. the dependence potential of gabapentin has not been evaluated in human studies.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - levetiracetam (unii: 44yrr34555) (levetiracetam - unii:44yrr34555) - levetiracetam 250 mg - levetiracetam tablets are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 1 month of age and older with epilepsy. levetiracetam tablets are indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy. levetiracetam tablets are indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. levetiracetam tablet is contraindicated in patients with a hypersensitivity to levetiracetam. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.4) ]. levetiracetam blood levels may decrease during pregnancy [see warnings and precautions (5.10)] . pregnancy category c there are no adequate and controlled studies in pregnant women. in animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. oral administration of levetiracetam to female rats throughout pregnancy and lactation led to increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre- and/or postnatally at doses ≥350 mg/kg/day (equivalent to the maximum recommended human dose of 3,000 mg [mrhd] on a mg/m2 basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1,800 mg/kg/day (6 times the mrhd on a mg/m2 basis). the developmental no effect dose was 70 mg/kg/day (0.2 times the mrhd on a mg/m2 basis). there was no overt maternal toxicity at the doses used in this study. oral administration of levetiracetam to pregnant rabbits during the period of organogenesis resulted in increased embryofetal mortality and increased incidences of minor fetal skeletal abnormalities at doses ≥600 mg/kg/day (4 times mrhd on a mg/m2 basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1,800 mg/kg/day (12 times the mrhd on a mg/m2 basis). the developmental no effect dose was 200 mg/kg/day (equivalent to the mrhd on a mg/m2 basis). maternal toxicity was also observed at 1,800 mg/kg/day. when levetiracetam was administered orally to pregnant rats during the period of organogenesis, fetal weights were decreased and the incidence of fetal skeletal variations was increased at a dose of 3,600 mg/kg/day (12 times the mrhd). 1,200 mg/kg/day (4 times the mrhd) was a developmental no effect dose. there was no evidence of maternal toxicity in this study. treatment of rats with levetiracetam during the last third of gestation and throughout lactation produced no adverse developmental or maternal effects at doses of up to 1,800 mg/kg/day (6 times the mrhd on a mg/m2 basis). pregnancy registry to provide information regarding the effects of in utero exposure to levetiracetam, physicians are advised to recommend that pregnant patients taking levetiracetam enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll free number 1-888-233-2334, and must be done by the patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. the effect of levetiracetam on labor and delivery in humans is unknown. levetiracetam is excreted in human milk. because of the potential for serious adverse reactions in nursing infants from levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. the safety and effectiveness of levetiracetam in the adjunctive treatment of partial onset seizures in pediatric patients age 1 month to 16 years old with epilepsy have been established [see clinical studies (14.1)] . the dosing recommendation in these pediatric patients varies according to age group and is weight-based [see dosage and administration (2.2)] . the safety and effectiveness of levetiracetam as adjunctive treatment of myoclonic seizures in adolescents 12 years of age and older with juvenile myoclonic epilepsy have been established [see clinical studies (14.2)] . the safety and effectiveness of levetiracetam as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in pediatric patients 6 years of age and older with idiopathic generalized epilepsy have been established [see clinical studies (14.3)] . a 3-month, randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of levetiracetam as adjunctive therapy in 98 (levetiracetam n=64, placebo n=34) pediatric patients, ages 4 to 16 years old, with partial seizures that were inadequately controlled. the target dose was 60 mg/kg/day. neurocognitive effects were measured by the leiter-r attention and memory (am) battery, which measures various aspects of a child's memory and attention. although no substantive differences were observed between the placebo and drug treated groups in the median change from baseline in this battery, the study was not adequate to assess formal statistical non-inferiority of the drug and placebo. the achenbach child behavior checklist (cbcl/6 to 18), a standardized validated tool used to assess a child’s competencies and behavioral/emotional problems, was also assessed in this study. an analysis of the cbcl/6 to 18 indicated on average a worsening in levetiracetam-treated patients in aggressive behavior, one of the eight syndrome scores [see warnings and precautions (5.1)] . studies of levetiracetam in juvenile rats (dosing from day 4 through day 52 of age) and dogs (dosing from week 3 through week 7 of age) at doses of up to 1,800 mg/kg/day (approximately 7 and 24 times, respectively, the maximum recommended pediatric dose of 60 mg/kg/day on a mg/m2 basis) did not indicate a potential for age-specific toxicity. there were 347 subjects in clinical studies of levetiracetam that were 65 and over. no overall differences in safety were observed between these subjects and younger subjects. there were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam in these patients. levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see clinical pharmacology (12.3)] . clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see clinical pharmacology (12.3)] . dose adjustment is recommended for patients with impaired renal function and supplemental doses should be given to patients after dialysis [see dosage and administration (2.5)] .

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals llc - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram 10 mg - citalopram tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)]. citalopram tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including maois such as linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.3), drug interactions (7)] . - taking pimozide because of risk of qt prolongation [see drug interactions (7)]. - with known hypersensitivity to citalopram or any of the inactive ingredients in citalopram tablets. reactions have included angioedema and anaphylaxis [see adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 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 (5.4)  and clinical considerations] . available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including citalopram hydrobromide, during pregnancy. there also are risks associated with untreated depression in pregnancy (see clinical considerations) . in animal reproduction studies, citalopram caused adverse embryo/fetal effects at doses that caused maternal toxicity (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of citalopram in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.4)] . fetal/neonatal adverse reactions neonates exposed to citalopram hydrobromide and other ssris late in third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. 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 findings are consistent with either a direct toxic effect of ssris or possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.3)] . data human data exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. animal data citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the maximum recommended human dose (mrhd) of 40 mg, based on mg/m2 body surface area. citalopram caused maternal toxicity of cns clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the mrhd. at this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). the no observed adverse effect level (noael) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the mrhd. citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the mrhd of 40 mg, based on mg/m2 body surface area. no maternal or embryofetal toxicity was observed. the noael for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the mrhd. citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the mrhd of 40 mg, based on mg/m2 body surface area. citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the mrhd. the noael for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the mrhd. in a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the mrhd. a noael was not determined in that study. risk summary data from the published literature report the presence of citalopram in human milk at relative infant doses ranging between 0.7 % to 9.4% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.78 to 4.3. there are reports of breastfed infants exposed to citalopram experiencing irritability, restlessness, excessive somnolence, decreased feeding, and weight loss (see clinical considerations). there is no information about effects of citalopram on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for citalopram hydrobromide and any potential adverse effects on the breastfed child from citalopram hydrobromide or from the underlying maternal condition. clinical considerations monitor breastfeeding infants for adverse reactions, such as irritability, restlessness, excessive somnolence, decreased feeding, and weight loss. the safety and effectiveness of citalopram hydrobromide have not been established in pediatric patients. two placebo-controlled trials in 407 pediatric patients with mdd have been conducted with citalopram hydrobromide, and the data were not sufficient to support use in pediatric patients. antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris in pediatric patients. of 4,422 patients in clinical studies of citalopram hydrobromide, 1,357 were 60 and over, 1,034 were 65 and over, and 457 were 75 and over. in two pharmacokinetic studies, citalopram auc was increased by 23% and 30%, respectively, in subjects ≥ 60 years of age as compared to younger subjects, and its half-life was increased by 30% and 50%, respectively [see clinical pharmacology (12.3)] . therefore, the maximum recommended dosage in patients 60 years of age and older is lower than younger patients [see dosage and administration (2.3), warnings and precautions (5.2)] . ssris, including citalopram hydrobromide, 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 (5.9)] . increased citalopram exposure occurs in patients with hepatic impairment. the maximum recommended dosage of citalopram hydrobromide is lower in patients with hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3)]. citalopram hydrobromide is not a controlled substance. animal studies suggest that the abuse liability of citalopram hydrobromide is low. citalopram hydrobromide has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with citalopram hydrobromide did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict, on the basis of this limited experience, the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, health care providers should carefully evaluate citalopram hydrobromide patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).