Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - colchicine (unii: sml2y3j35t) (colchicine - unii:sml2y3j35t) - colchicine 0.6 mg - colchicine capsules are indicated for prophylaxis of gout flares in adults. limitations of use: the safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied. colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes. patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both p-glycoprotein and cyp3a4 inhibitors [see drug interactions (7)] . combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. patients with both renal and hepatic impairment should not be given colchicine capsules.  there are no adequate and well-controlled studies with colchicine capsules in pregnant women. colchicine crosses the human placenta. developmental studies in animals were not conducted with colchicine capsules, however published animal reproduction and development studies with colchicine demonstrated embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range. colchicine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the effect of colchicine on labor and delivery is unknown. colchicine is excreted into human milk. limited information suggests that infants exclusively breastfed receive less than 10 percent of the maternal weight-adjusted dose. while there are no published reports of adverse effects in breast-feeding infants of mothers taking colchicine, colchicine can affect gastrointestinal cell renewal and permeability. caution should be exercised and breastfeeding infants should be observed for adverse effects when colchicine capsules is administered to a nursing woman.   gout is rare in pediatric patients; the safety and effectiveness of colchicine capsules in pediatric patients has not been evaluated in controlled studies. because of the increased incidence of decreased renal function in the elderly population, and the higher incidence of other co-morbid conditions in the elderly population requiring the use of other medications, reducing the dosage of colchicine when elderly patients are treated with colchicine should be carefully considered. no dedicated pharmacokinetic study has been conducted using colchicine capsules in patients with varying degrees of renal impairment.  colchicine is known to be excreted in urine in humans and the presence of severe renal impairment has been associated with colchicine toxicity. urinary clearance of colchicine and its metabolites may be decreased in patients with impaired renal function. dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe renal impairment. colchicine is not effectively removed by hemodialysis. patients who are undergoing hemodialysis should be monitored carefully for colchicine toxicity. no dedicated pharmacokinetic study using colchicine capsules has been conducted in patients with varying degrees of hepatic impairment. colchicine is known to be metabolized in humans and the presence of severe hepatic impairment has been associated with colchicine toxicity. hepatic clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment. dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment. tolerance, abuse, or dependence from colchicine has not been reported.

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - codeine sulfate (unii: 11qv9bs0cb) (codeine anhydrous - unii:ux6owy2v7j) - codeine sulfate tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate 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 codeine sulfate tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products] : codeine sulfate 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. codeine sulfate tablets are contraindicated for: codeine sulfate tablets are also 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 (5.4)] . available data with codeine sulfate tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, codeine administration during organogenesis has been shown to produce delayed ossification in the offspring of mice at 1.4 times maximum recommended human dose (mrhd) of 360 mg/day, embryolethal and fetotoxic effects in the offspring of rats and hamsters at approximately 2 to 3 times the mrhd, and cranial malformations/cranioschisis in the offspring of hamsters between 2 and 8 times the mrhd [see data ]. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations: fetal/neonatal adverse reactions: use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor 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. codeine sulfate 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 codeine sulfate 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: studies on the reproductive and developmental effects of codeine have been reported in the published literature in hamsters, rats, mice and rabbits. in a study in which pregnant hamsters were administered 150 mg/kg twice daily of codeine (oral; approximately 7 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) during organogenesis cranial malformations (i.e., meningoencephalocele) in several fetuses were reported; as well as the observation of increases in the percentage of resorptions per litter. doses of 50 and 150 mg/kg, bid resulted in fetotoxicity as demonstrated by decreased fetal body weight. in an earlier study in hamsters, single oral doses of 73 to 360 mg/kg level on gestation day 8 (oral; approximately 2 to 8 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis), reportedly produced cranioschisis in all of the fetuses examined. in studies in rats, doses at the 120 mg/kg level (oral; approximately 3 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) during organogenesis, in the toxic range for the adult animal, were associated with an increase in embryo resorption at the time of implantation. in pregnant mice, a single 100 mg/kg dose (subcutaneous; approximately 1.4 times the recommended daily dose of 360 mg/day for adults on a mg/mg2 basis) administered between gestation day 7 and 12 reportedly resulted in delayed ossification in the offspring. no teratogenic effects were observed in rabbits administered up to 30 mg/kg (approximately 2 times the maximum recommended daily dose of 360 mg/day for adults on a mg/m2 basis) of codeine during organogenesis. codeine (30 mg/kg) administered subcutaneously to pregnant rats during pregnancy and for 25 days after delivery increased neonatal mortality at birth. this dose is 0.8 times the maximum recommended human dose of 360 mg/day on a body surface area comparison. risk summary: codeine and its active metabolite, morphine, are present in human milk. there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk. women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants. in women with normal codeine metabolism (normal cyp2d6 activity), the amount of codeine secreted into human milk is low and dose-dependent. there is no information on the effects of codeine on milk production. because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with codeine sulfate tablets [see warnings and precautions (5.4)] . clinical considerations: if infants are exposed to codeine sulfate tablets 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 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)] . the safety and effectiveness of codeine sulfate tablets in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received codeine [see warnings and precautions (5.6)] . in most of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6 or high morphine concentrations). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of codeine. because of the risk of life-threatening respiratory depression and death: elderly patients (aged 65 years or older) may have increased sensitivity to codeine. 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 codeine sulfate tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.9)] . codeine 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. no formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of codeine in this patient population are unknown. start these patients with a lower than normal dosage of codeine sulfate tablets or with longer dosing intervals and titrate slowly while regularly evaluating for signs of respiratory depression, sedation, and hypotension. codeine pharmacokinetics may be altered in patients with renal failure. clearance may be decreased and the metabolites may accumulate to much higher plasma levels in patients with renal failure as compared to patients with normal renal function. start these patients with a lower than normal dosage of codeine sulfate tablets or with longer dosing intervals and titrate slowly while regularly evaluating for signs of respiratory depression, sedation, and hypotension. codeine sulfate tablets contain codeine, a schedule ii controlled substance. codeine sulfate tablets contains codeine, 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 codeine sulfate tablets increases risk of overdosage, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of codeine sulfate 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 codeine sulfate tablets abuse include those with a history of prolonged use of any opioid, including products containing codeine, those with a history of drug or alcohol abuse, or those who use codeine sulfate 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. codeine sulfate 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 codeine sulfate tablets: abuse of codeine sulfate tablets poses a risk of overdose and death. the risk is increased with concurrent use of codeine sulfate tablets with alcohol and/or other cns depressants. codeine sulfate 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 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 codeine sulfate tablets in a patient physically dependent on opioids. rapid tapering of codeine sulfate 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 codeine sulfate tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of codeine sulfate 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 (5.16)]. 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)] .

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - methadone hydrochloride (unii: 229809935b) (methadone - unii:uc6vbe7v1z) - methadone hydrochloride 5 mg in 5 ml - methadone hydrochloride oral solution is indicated for the: limitations of use: limitations of use: methadone hydrochloride oral solution is contraindicated in patients with: risk summary the majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. pregnant women involved in methadone maintenance programs have been reported to have improved prenatal care leading to reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. several factors, including maternal use of illicit drugs, nutrition, infection and psychosocial circumstances, complicate the interpretation of investigations of the children of women who take methadone during pregnancy. information is limited regarding dose and duration of methadone use during pregnancy, and most maternal exposure in these studies appear

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

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)] .

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - alendronate sodium (unii: 2uy4m2u3ra) (alendronic acid - unii:x1j18r4w8p) - alendronate sodium is indicated for the treatment of osteoporosis in postmenopausal women. in postmenopausal women, alendronate increases bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures) [see clinical studies ( 14.1) ] . alendronate sodium is indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies ( 14.3) ] . the optimal duration of use has not been determined. the safety and effectiveness of alendronate for the treatment of osteoporosis are based on clinical data of four years duration. all patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. patients who discontinue therapy should have their risk for fracture re-evaluated periodically. alendronate sodium is contraindicated in patients with the following conditions: risk summary: availabl

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - haloperidol lactate (unii: 6387s86pk3) (haloperidol - unii:j6292f8l3d) - haloperidol 5 mg in 1 ml - haloperidol is indicated for the treatment of patients with schizophrenia. haloperidol injection is contraindicated in patients with: - severe toxic central nervous system depression or comatose states from any cause. - hypersensitivity to this drug – hypersensitivity reactions have included anaphylactic reaction and angioedema (see warnings, hypersensitivity reactions and adverse reactions ). - parkinson’s disease (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ). - dementia with lewy bodies (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ).

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - haloperidol lactate (unii: 6387s86pk3) (haloperidol - unii:j6292f8l3d) - haloperidol is indicated for the treatment of patients with schizophrenia. haloperidol injection is contraindicated in patients with: - severe toxic central nervous system depression or comatose states from any cause. - hypersensitivity to this drug – hypersensitivity reactions have included anaphylactic reaction and angioedema (see warnings, hypersensitivity reactions and adverse reactions ). - parkinson’s disease (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ). - dementia with lewy bodies (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ).

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - haloperidol decanoate (unii: ac20pj4101) (haloperidol - unii:j6292f8l3d) - haloperidol decanoate injection is indicated for the treatment of patients with schizophrenia who require prolonged parenteral antipsychotic therapy. since the pharmacologic and clinical actions of haloperidol decanoate injection are attributed to haloperidol as the active medication,contraindications , warnings , and additional information are those of haloperidol, modified only to reflect the prolonged action. haloperidol is contraindicated in patients with: - severe toxic central nervous system depression or comatose states from any cause. - hypersensitivity to this drug – hypersensitivity reactions have included anaphylactic reaction and angioedema (see warnings, hypersensitivity reactions and adverse reactions ). - parkinson’s disease (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ). - dementia with lewy bodies (see warnings, neurological adverse reactions in patients with parkinson’s disease or dementia with lewy bodies ).

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - ciprofloxacin hydrochloride (unii: 4ba73m5e37) (ciprofloxacin - unii:5e8k9i0o4u) - ciprofloxacin 250 mg - ciprofloxacin tablets are indicated in adult patients for treatment of skin and skin structure infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, proteus vulgaris, providencia stuartii, morganella morganii, citrobacter freundii, pseudomonas aeruginosa, methicillin-susceptible staphylococcus aureus, methicillin-susceptible staphylococcus epidermidis, or streptococcus pyogenes. ciprofloxacin tablets are indicated in adult patients for treatment of bone and joint infections caused by enterobacter cloacae, serratia marcescens, or pseudomonas aeruginosa. ciprofloxacin tablets are indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by escherichia coli, pseudomonas aeruginosa, proteus mirabilis, klebsiella pneumoniae, or bacteroides fragilis. ciprofloxacin tablets are indicated in adult patients for treatment of infectious diarrhea caused by escherichia coli ( enterotoxigenic isolates), campylobacter jejuni, shigella boydii †, shigella dysenteriae, shigella flexneri or shigella sonnei † when antibacterial therapy is indicated. † although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients. ciprofloxacin tablets are indicated in adult patients for treatment of typhoid fever (enteric fever) caused by salmonella typhi. the efficacy of ciprofloxacin in the eradication of the chronic typhoid carrier state has not been demonstrated. ciprofloxacin tablets are indicated in adult patients for treatment of uncomplicated cervical and urethral gonorrhea due to neisseria gonorrhoeae [see warnings and precautions (5.17)]. ciprofloxacin tablets are indicated in adults and pediatric patients from birth to 17 years of age for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized bacillus anthracis. ciprofloxacin serum concentrations achieved in humans served as a surrogate endpoint reasonably likely to predict clinical benefit and provided the initial basis for approval of this indication.1 supportive clinical information for ciprofloxacin for anthrax post-exposure prophylaxis was obtained during the anthrax bioterror attacks of october 2001 [see clinical studies ( 14.2 )]. ciprofloxacin tablets are indicated for treatment of plague, including pneumonic and septicemic plague, due to yersinia pestis (y. pestis) and prophylaxis for plague in adults and pediatric patients from birth to 17 years of age. efficacy studies of ciprofloxacin could not be conducted in humans with plague for feasibility reasons. therefore this indication is based on an efficacy study conducted in animals only [see clinical studies ( 14.3 ) ]. ciprofloxacin tablets are indicated in adult patients for treatment of chronic bacterial prostatitis caused by escherichia coli or proteus mirabilis. ciprofloxacin tablets are indicated in adult patients for treatment of lower respiratory tract infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, pseudomonas aeruginosa, haemophilus influenzae, haemophilus parainfluenzae, or streptococcus pneumoniae. ciprofloxacin tablets are not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to streptococcus pneumoniae . ciprofloxacin tablets are indicated for the treatment of acute exacerbations of chronic bronchitis (aecb) caused by moraxella catarrhalis. because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1 – 5.16 )] and for some patients aecb is self-limiting, reserve ciprofloxacin tablets for treatment of aecb in patients who have no alternative treatment options. urinary tract infections in adults ciprofloxacin tablets are indicated in adult patients for treatment of urinary tract infections caused by escherichia coli , klebsiella pneumoniae , enterobacter cloacae , serratia marcescens , proteus mirabilis , providencia rettgeri , morganella morganii , citrobacter koseri , citrobacter freundii , pseudomonas aeruginosa , methicillin-susceptible staphylococcus epidermidis , staphylococcus saprophyticus , or enterococcus faecalis . acute uncomplicated cystitis ciprofloxacin tablets are indicated in adult female patients for treatment of acute uncomplicated cystitis caused by escherichia coli or staphylococcus saprophyticus. because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions (5.1-5.16)] and for some patients acute uncomplicated cystitis is self-limiting, reserve ciprofloxacin tablets for treatment of acute uncomplicated cystitis in patients who have no alternative treatment options. complicated urinary tract infection and pyelonephritis in pediatric patients ciprofloxacin tablets are indicated in pediatric patients aged one to 17 years of age for treatment of complicated urinary tract infections (cuti) and pyelonephritis due to escherichia coli [see use in specific populations (8.4)] . although effective in clinical trials, ciprofloxacin tablets are not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls, including reactions related to joints and/or surrounding tissues. ciprofloxacin tablets, like other fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals [see warnings and precautions (5.13), adverse reactions (6.1), usein specific populations (8.4) and nonclinical toxicology (13.2)]. ciprofloxacin tablets are indicated in adult patients for treatment of acute sinusitis caused by haemophilus influenzae, streptococcus pneumoniae, or moraxella catarrhalis. because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1 - 5.16 )] and for some patients acute sinusitis is self-limiting, reserve ciprofloxacin tablets for treatment of acute sinusitis in patients who have no alternative treatment options. to reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin tablets and other antibacterial drugs, ciprofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. if anaerobic organisms are suspected of contributing to the infection, appropriate therapy should be administered. appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ciprofloxacin. therapy with ciprofloxacin tablets may be initiated before results of these tests are known; once results become available appropriate therapy should be continued. as with other drugs, some isolates of pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ciprofloxacin. culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.  ciprofloxacin tablets are contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antibacterials, or any of the product components [see warnings and precautions ( 5.7 ) ]. concomitant administration with tizanidine is contraindicated [see drug interactions ( 7 ) ]. risk summary prolonged experience with ciprofloxacin in pregnant women over several decades, based on available published information from case reports, case control studies and observational studies on ciprofloxacin administered during pregnancy, have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see data). oral administration of ciprofloxacin during organogenesis at doses up to 100 mg/kg to pregnant mice and rats, and up to 30 mg/kg to pregnant rabbits did not cause fetal malformations (see data). these doses were up to 0.3, 0.6, and 0.4 times the maximum recommended clinical oral dose in mice, rats, and rabbits, respectively, based on body surface area. 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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data while available studies cannot definitively establish the absence of risk, published data from prospective observational studies over several decades have not established an association with ciprofloxacin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. available studies have methodological limitations including small sample size and some of them are not specific for ciprofloxacin. a controlled prospective observational study followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. in utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. the reported rates of major congenital malformations were 2.2% for the fluoroquinolone group and 2.6% for the control group (background incidence of major malformations is 1–5%). rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to one year of age in the ciprofloxacin exposed children. another prospective follow-up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). there were 70 ciprofloxacin exposures, all within the first trimester. the malformation rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both within background incidence ranges. no specific patterns of congenital abnormalities were found. the study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. no differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women exposed to ciprofloxacin during pregnancy. however, these small postmarketing epidemiology studies, of which most experience is from short term, first trimester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. animal data developmental toxicology studies have been performed with ciprofloxacin in rats, mice, and rabbits. in rats and mice, oral doses up to 100 mg/kg administered during organogenesis (gestation days, gd, 6-17) were not associated with adverse developmental outcomes, including embryofetal toxicity or malformations. in rats and mice, a 100 mg/kg dose is approximately 0.6 and 0.3 times the maximum daily human oral dose (1500 mg/day) based upon body surface area, respectively. in a series of rabbit developmental toxicology studies, does received oral or intravenous ciprofloxacin for one of the following 5 day periods: gd 6 to 10, gd 10 to 14, or gd 14 to 18, intended to cover the period of organogenesis. this was an attempt to mitigate the gastrointestinal intolerance observed in rabbits that receive antibacterials manifested by reduced maternal food consumption and weight loss, that can lead to embryofetal resorption or spontaneous abortion. an oral ciprofloxacin dose of 100 mg/kg (approximately 1.3 times the highest recommended clinical oral dose based on body surface area) caused excessive maternal toxicity confounding evaluation of the fetuses. a 30 mg/kg oral dose (approximately 0.4 times the highest recommended clinical oral dose) was associated with suppression of maternal and fetal body weight gain, but fetal malformations were not observed. intravenous administration of doses up to 20 mg/kg (approximately 0.3 times the highest recommended clinical oral dose based upon body surface area) to pregnant rabbits was not maternally toxic and neither embryofetal toxicity nor fetal malformations were observed. in peri-and post-natal studies, rats received ciprofloxacin doses up to 200 mg/kg/day (oral) or up to 30 mg/kg/day (subcutaneous) from gd 16 to 22 days postpartum. the 200 mg/kg dose is approximately 1.3-times the maximum recommended clinical oral dose based on body surface area. neither maternal toxicity nor adverse effects on growth and development of the pups were observed, including no sign of arthropathy on the rear leg joints of the pups. ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested when administered directly [see warnings and precautions (5.13) and nonclinical toxicology 13.2]. risk summary published literature reports that ciprofloxacin is present in human milk following intravenous and oral administration. there is no information regarding effects of ciprofloxacin tablets on milk production or the breastfed infant. because of the potential risk of serious adverse reactions in breastfed infants, including arthropathy shown in juvenile animal studies [see use in specific populations (8.4),  (clinical considerations)], for most indications a lactating woman may consider pumping and discarding breast milk during treatment with ciprofloxacin tablets and an additional two days (five half-lives) after the last dose. alternatively, advise a woman that breastfeeding is not recommended during treatment with ciprofloxacin tablets and for an additional two days (five half-lives) after the last dose. however, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on ciprofloxacin tablets may be acceptable [see dosage and administration (2.2) , pediatric use (8.4), and clinical studies (14.2)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ciprofloxacin tablets and any potential adverse effects on the breastfed child from ciprofloxacin tablets or from the underlying maternal condition. clinical considerations ciprofloxacin may cause intestinal flora alteration of the breastfeeding infant. advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash). although effective in clinical trials, ciprofloxacin tablets are not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls. quinolones, including ciprofloxacin tablets, cause arthropathy (arthralgia, arthritis), in juvenile animals [see warnings and precautions ( 5.13 )   and nonclinical toxicology ( 13.2 ) ] . complicated urinary tract infection and pyelonephritis ciprofloxacin tablets are indicated for the treatment of cuti and pyelonephritis due to escherichia coli in pediatric patients 1 to 17 years of age. although effective in clinical trials, ciprofloxacin tablets are not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to the controls, including events related to joints and/or surrounding tissues [see adverse reactions (6.1) and clinical studies (14.1)]. inhalational anthrax (post-exposure) ciprofloxacin tablets are indicated in pediatric patients from birth to 17 years of age, for inhalational anthrax (post-exposure). the risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients is appropriate [see dosage and administration ( 2.2 )  and clinical studies ( 14.2 ) ]. plague ciprofloxacin tablets are indicated in pediatric patients from birth to 17 years of age, for treatment of plague, including pneumonic and septicemic plague due to yersinia pestis (y. pestis) and prophylaxis for plague. efficacy studies of ciprofloxacin tablets could not be conducted in humans with pneumonic plague for feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals. the risk-benefit assessment indicates that administration of ciprofloxacin tablets to pediatric patients is appropriate [s ee indications and usage ( 1.8 ), dosage and administration ( 2.2 ) and clinical studies ( 14.3 ) ] . geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as ciprofloxacin tablets. this risk is further increased in patients receiving concomitant corticosteroid therapy. tendinitis or tendon rupture can involve the achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. caution should be used when prescribing ciprofloxacin tablets to elderly patients especially those on corticosteroids. patients should be informed of this potential adverse reaction and advised to discontinue ciprofloxacin tablets and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [s ee boxed warning , warnings and precautions ( 5.2 ),  and adverse reactions ( 6.2 ) ] . epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see warnings and precautions (5 .9 ) ]. in a retrospective analysis of 23 multiple-dose controlled clinical trials of ciprofloxacin tablets encompassing over 3500 ciprofloxacin-treated patients, 25% of patients were greater than or equal to 65 years of age and 10% were greater than or equal to 75 years of age. 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 on any drug therapy cannot be ruled out. ciprofloxacin is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. no alteration of dosage is necessary for patients greater than 65 years of age with normal renal function. however, since some older individuals experience reduced renal function by virtue of their advanced age, care should be taken in dose selection for elderly patients, and renal function monitoring may be useful in these patients [s ee dosage and administration ( 2.3 )  a nd clinical pharmacology ( 12.3 ) ] . in general, elderly patients may be more susceptible to drug-associated effects on the qt interval. therefore, precaution should be taken when using ciprofloxacin tablets with concomitant drugs that can result in prolongation of the qt interval (for example, class ia or class iii antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known qt prolongation, uncorrected hypokalemia) [s ee warnings and precautions ( 5.12 ) ] . ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. these alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction [s ee dosage and administration ( 2.3 )     and cli nical pharmacology ( 12.3 ) ] .   in preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. the pharmacokinetics of ciprofloxacin in patients with acute hepatic insufficiency, have not been studied.

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate 5 mg - zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. zolpidem tartrate tablets have been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see clinical studies (14) ]. the clinical trials performed in support of efficacy were 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment. zolpidem tartrate is contraindicated in patients with known hypersensitivity to zolpidem tartrate or to any of the inactive ingredients in the formulation. observed reactions include anaphylaxis and angioedema [see warnings and precautions (5.2)]. there are no adequate and well-controlled studies in pregnant women. zolpidem tartrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. administration of zolpidem to pregnant rats and rabbits resulted in adverse effects on offspring development at doses greater than the zo