USA - engelsk - NLM (National Library of Medicine)

nexgen pharma, inc. - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u) - codeine phosphate 54.3 mg - codeine phosphate and chlorpheniramine maleate is indicated for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older. important limitations of use not indicated for pediatric patients under 18 years of age [see use in special population (8.4)] patients with known hypersensitivity to codeine, chlorpheniramine or any of the inactive ingredients of codeine phosphate and chlorpheniramine maleate. persons known to be hypersensitive to certain other opioids may exhibit cross-sensitivity to codeine. teratogenic effects pregnancy category c there are no adequate and well-controlled studies of codeine phosphate and chlorpheniramine maleate in pregnant women. reproductive toxicity studies have not been conducted with codeine phosphate and chlorpheniramine maleate; however, studies are available with individual active ingredients or related active ingredients. because animal reproduction studies are not always predictive of human response, co

USA - engelsk - NLM (National Library of Medicine)

lannett company, inc. - codeine sulfate (unii: 11qv9bs0cb) (codeine anhydrous - unii:ux6owy2v7j) - codeine sulfate 15 mg - 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, even at recommended doses [ s ee 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]: - have not been tolerated, or are not expected to be tolerated. have not been tolerated, or are not expected to be tolerated. - have not provided adequate analgesia, or are not expected to provide adequate analgesia. have not provided adequate analgesia, or are not expected to provide adequate analgesia. codeine sulfate tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions ( 5.4 )] . - post-operative management in children younger than 18 years of age following tonsillect

USA - engelsk - NLM (National Library of Medicine)

lake erie medical & surgical supply dba quality care products llc - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), promethazine hydrochloride (unii: r61zeh7i1i) (promethazine - unii:ff28ejq494) - codeine phosphate 10 mg in 5 ml - promethazine with codeine syrup is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold. the combination of promethazine hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age, because the combination may cause fatal respiratory depression in this age population. codeine is contraindicated in patients with a known hypersensitivity to the drug. promethazine is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. the combination of promethazine hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age. concomitant administration of promethazine products with other respiratory depressants has an association with resp

USA - engelsk - NLM (National Library of Medicine)

par pharmaceutical - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), promethazine hydrochloride (unii: r61zeh7i1i) (promethazine - unii:ff28ejq494), phenylephrine hydrochloride (unii: 04ja59tnsj) (phenylephrine - unii:1ws297w6mv) - codeine phosphate 10 mg in 5 ml - promethazine vc with codeine oral solution is indicated for the temporary relief of coughs and upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold in patients 18 years of age and older. important limitations of use - not indicated for pediatric patients under 18 years of age [see use in specific populations (8.4) ]. - contraindicated in pediatric patients under 12 years of age [see contraindications (4) and use in specific populations (8.4) ]. - contraindicated in pediatric patients 12 to 18 years of age after tonsillectomy or adenoidectomy [see contraindications (4) and use in specific populations (8.4) ]. - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1) ], reserve promethazine vc with codeine oral solution for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough h

USA - engelsk - NLM (National Library of Medicine)

pai holdings, llc - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), promethazine hydrochloride (unii: r61zeh7i1i) (promethazine - unii:ff28ejq494), phenylephrine hydrochloride (unii: 04ja59tnsj) (phenylephrine - unii:1ws297w6mv) - promethazine vc with codeine oral solution is indicated for the temporary relief of coughs and upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold in patients 18 years of age and older. important limitations of use • not indicated for pediatric patients under 18 years of age [see use in specific populations (8.4)]. • contraindicated in pediatric patients under 12 years of age [see contraindications (4) and use in specific populations (8.4)]. • contraindicated in pediatric patients 12 to 18 years of age after tonsillectomy or adenoidectomy [see contraindications (4) and use in specific populations (8.4)]. • because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)], reserve promethazine vc with codeine oral solution for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks,and in whom an adequate assessment of the etiology of the cough has been made. promethazine vc with codeine oral solution is contraindicated for: • all children younger than 12 years of age [ see warnings and precautions ( 5.2, 5.3, 5.5 ), use in specific populations ( 8.4) ]. • postoperative pain management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see warnings and precautions ( 5.2, 5.3) ]. promethazine vc with codeine oral solution is also contraindicated in patients with: • significant respiratory depression [ see warnings and precautions ( 5.2) ]. • acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [ see warnings and precautions ( 5.6) ]. • known or suspected gastrointestinal obstruction, including paralytic ileus [ see warnings and precautions ( 5.11) ]. • narrow angle glaucoma, urinary retention, severe hypertension, severe coronary artery disease, or peripheral vascular insufficiency (ischemia    may result with risk of gangrene or thrombosis of compromised vascular beds) [ see warnings and precautions ( 5.13 )]. • a history of an idiosyncratic reaction to promethazine or to other phenothiazines [ see warnings and precautions ( 5.15) ]. • concurrent use of monoamine oxidase inhibitors (maois) or use of maois within 14 days [ see warnings and precautions ( 5.17 ) and drug    interactions ( 7.6) ]. • hypersensitivity to codeine, promethazine, phenylephrine, or any of the inactive ingredients in promethazine vc with codeine oral solution [ see    adverse reactions ( 6) ]. persons known to be hypersensitive to certain other opioids may exhibit cross-reactivity to codeine. risk summary promethazine vc with codeine oral solution is not recommended for use in pregnant women, including during or immediately prior to labor. prolonged use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome [ see warnings and precautions ( 5.20 ), clinical considerations ]. there are no available data with promethazine vc with codeine oral solution use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. published studies with codeine have reported inconsistent findings and have important methodological limitations ( see data ). there are reports of respiratory depression when codeine is used during labor and delivery ( see clinical considerations ). reproductive toxicity studies have not been conducted with promethazine vc with codeine oral solution; however, studies are available with individual active ingredients ( see data ). in animal reproduction studies, codeine administered by the oral route to pregnant rats during the period of organogenesis increased resorptions and decreased fetal weights at a dose approximately 26 times the maximum recommended human dose (mrhd) in the presence of maternal toxicity ( see data ). for pregnant mice and rats that received promethazine at doses 0.15 to 3 times the mrhd, during various periods of gestation, there were findings of increased fetal resorptions and skeletal fragility, decreased pup weight, and developmental delays of pups ( see data ). in studies with normotensive pregnant rabbits, which received phenylephrine during the period of organogenesis or later, there were findings of increased fetal lethality, adverse placental effects, and possible teratogenic effects at subcutaneous doses approximately 0.8 times the mrhd on a mg/m2 basis. premature labor was also observed when treatment was initiated during the second trimester or later ( see data ). based on the animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [ see warnings and precautions ( 5.20 )]. maternal use of phenylephrine can cause fetal tachycardia. 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. opioids, including promethazine vc with codeine oral solution, 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 opioids during labor for signs of excess sedation and respiratory depression. data human data published data from case-control and observational studies on codeine use during pregnancy are inconsistent in their findings. some studies of codeine exposure showed an increased risk of overall congenital malformations while others did not. an increased risk of specific malformations with codeine exposure such as respiratory malformations, spina bifida and congenital heart defects were reported in some studies. the majority of studies examining the use of phenylephrine and promethazine in pregnancy did not find an association with an increased risk of congenital anomalies. in the few studies reporting an association, no consistent pattern of malformations was noted. most of the studies, both positive and negative, were limited by small sample size, recall bias and lack of information regarding dose and timing of exposure. animal data reproductive toxicity studies have not been conducted with promethazine vc with codeine oral solution; however, studies are available with individual active ingredients. codeine in an embryofetal development study in pregnant rats dosed throughout the period of organogenesis, codeine increased resorptions and decreased fetal weights at a dose approximately 26 times the mrhd (on a mg/m 2 basis with a maternal oral dose of 120 mg/kg/day); however, these effects occurred in the presence of maternal toxicity. in embryofetal development studies with pregnant rabbits and mice dosed throughout the period of organogenesis, codeine produced no adverse developmental effects at doses approximately 13 and 66 times, respectively, the mrhd (on a mg/m 2 basis with maternal oral doses of 30 mg/kg/day in rabbits and 600 mg/kg/day in mice). promethazine in pregnant mice dosed during the period of implantation from gestation days 1 to 5, promethazine increased resorption at doses approximately 0.2 times the mrhd (on a mg/m2 basis with maternal intraperitoneal and subcutaneous doses up to 1 mg/kg/day). in pregnant rats dosed during the period of organogenesis from gestation days 5 to 16, promethazine hydrochloride induced complete resorption at doses approximately 6 times the mrhd (on a mg/m 2 basis with maternal oral doses up to 20 mg/kg/day). in pregnant rats dosed during the period of organogenesis from gestation days 7 to 13, promethazine resulted in skeletal fragility of pups at doses approximately 3 times the mrhd (on a mg/m 2 basis with maternal oral doses up to 10 mg/kg/day). in pregnant rats dosed during the period of organogenesis from gestation days 10 to 12, promethazine resulted in decreased weight and delays in initial occurrence of behavioral/reflex of pups at doses approximately 3 times the mrhd (on a mg/m 2 basis with maternal oral doses up to 10 mg/kg/day). the relevance of these findings to humans is unclear. phenylephrine in studies with normotensive pregnant rabbits, which received phenylephrine during the period of organogenesis or later, there were findings of fetal deaths, adverse histopathology findings in the placenta (necrosis, calcification and thickened vascular walls with narrowed lumen), and possible teratogenic effects (one incidence of clubbed feet, partial development of the intestine) at doses approximately 0.8 times the mrhd (on a mg/m 2 basis with a maternal subcutaneous dose of 1 mg/kg/day). premature labor was also observed when treatment was initiated during the second trimester or later. mean percentage of implantations in rabbits was decreased by injection of phenylephrine. risk summary 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 promethazine vc with codeine oral solution [see warnings and precautions ( 5.3) ]. there are no data on the presence of promethazine vc with codeine oral solution in human milk, the effects of promethazine vc with codeine oral solution on the breastfed infant, or the effects of promethazine vc with codeine oral solution on milk production; however, data are available with codeine and promethazine. codeine 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 one infant) 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 the codeine on milk production. promethazine there are no data on the presence of promethazine in human milk. however, direct oral administration of promethazine has been associated with respiratory depression, including fatalities, in pediatric patients [ see warnings and precautions ( 5.4) ]. promethazine has been shown to decrease basal prolactin levels in non-nursing women, and therefore may affect milk production. phenylephrine there are no data on the presence of phenylephrine in human milk or on its effects on the breastfed infant. phenylephrine is known to be poorly absorbed orally. animal data indicate that phenylephrine can decrease milk production and pharmacologically similar vasoconstrictors, such as pseudoephedrine, decrease milk production in lactating women after oral use. clinical considerations infants exposed to promethazine vc with codeine oral solution 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 is stopped, or when breastfeeding is stopped. infertility chronic use of opioids, such as codeine, a component of promethazine vc with codeine oral solution, 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) and clinical pharmacology ( 12.2) ]. promethazine vc with codeine oral solution is not indicated for use in patients younger than 18 years of age because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks for use of codeine in these patients [ see indications ( 1) and warnings and precautions ( 5.5) ]. life-threatening respiratory depression and death have occurred in children who received codeine [see warnings and precautions ( 5.2) ]. 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 (ie, 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. life-threatening respiratory depression and death have also occurred in children who received promethazine [see warnings and precautions ( 5.4) ]. because of the risk of life-threatening respiratory depression and death: - promethazine vc with codeine oral solution is contraindicated for all children younger than 12 years of age [see contraindications ( 4) ]. - promethazine vc with codeine oral solution is contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see contraindications ( 4) ]. - avoid the use of promethazine vc with codeine oral solution in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression [see warnings and precautions ( 5.3, 5.6) ]. clinical studies have not been conducted with promethazine vc with codeine oral solution in geriatric populations. use caution when considering the use of promethazine vc with codeine oral solution in patients 65 years of age or older. elderly patients may have increased sensitivity to codeine; greater frequency of decreased hepatic, renal, or cardiac function; or concomitant disease or other drug therapy [see warnings and precautions ( 5.6) ]. respiratory depression is the chief risk for elderly patients treated with opioids, including promethazine vc with codeine oral solution.  respiratory depression has occurred after large initial doses of opioids were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration [see warnings and precautions ( 5.6, 5.10) ]. 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, monitor these patients closely for respiratory depression, sedation, and hypotension. the pharmacokinetics of promethazine vc with codeine oral solution has not been characterized in patients with renal impairment.  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. promethazine vc with codeine oral solution should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for respiratory depression, sedation, and hypotension. no formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of promethazine vc with codeine oral solution in this patient population are unknown. promethazine vc with codeine oral solution should be used with caution in patients with impairment of hepatic function, and patients should be monitored closely for respiratory depression, sedation, and hypotension. promethazine vc with codeine oral solution contains codeine, a schedule v controlled substance. codeine promethazine vc with codeine oral solution contains codeine, a substance with a high potential for abuse similar to other opioids including morphine and codeine. promethazine vc with codeine oral solution 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, since use of opioid analgesic and antitussive 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 health care 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. health care 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. promethazine vc with codeine oral solution, 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 promethazine vc with codeine oral solution promethazine vc with codeine oral solution is for oral use only. abuse of promethazine vc with codeine oral solution poses a risk of overdose and death. the risk is increased with concurrent use of promethazine vc with codeine oral solution with alcohol and other central nervous system depressants [see warnings and precautions ( 5.10 )]. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. psychological dependence, physical dependence, and tolerance may develop upon repeated administration of opioids; therefore, promethazine vc with codeine oral solution should be prescribed and administered for the shortest duration that is consistent with individual patient treatment goals and patients should be reevaluated prior to refills [see dosage and administration ( 2.3) and warnings and precautions ( 5.1) ]. physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develop after a few days of opioid therapy. if promethazine vc with codeine oral solution is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (eg, naloxone, nalmefene), mixed agonist/antagonist analgesics (eg, pentazocine, butorphanol, nalbuphine), or partial agonists (eg, buprenorphine). some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 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) ].

USA - engelsk - 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)] .

USA - engelsk - NLM (National Library of Medicine)

northwind pharmaceuticals - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - codeine phosphate 30 mg - acetaminophen and codeine phosphate 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, even at recommended doses [see warnings], reserve acetaminophen and codeine phosphate tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] have not provided adequate analgesia, or are not expected to provide adequate analgesia have not been tolerated, or are not expected to be tolerated please review the manufacturer's complete drug information available from the fda at www.fda.gov permanent link: https://dailymed.nlm.nih.gov/dailymed/druginfo.cfm?setid=02386806-02d4-47e3-9c8b-7810146ee795 acetaminophen and codeine phosphate tablets are contraindicated in patients with: patients with significant respiratory depression [see warnings].

USA - engelsk - NLM (National Library of Medicine)

apotheca inc - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), promethazine hydrochloride (unii: r61zeh7i1i) (promethazine - unii:ff28ejq494) - codeine phosphate 10 mg in 5 ml - promethazine hydrochloride and codeine phosphate syrup is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold. the combination of promethazine hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age, because the combination may cause fatal respiratory depression in this age population. codeine sulfate is contraindicated for postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy. codeine is contraindicated in patients with a known hypersensitivity to the drug. promethazine is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. promethazine hydrochloride and codeine phosphate syrup is a schedule v controlled substance

USA - engelsk - NLM (National Library of Medicine)

janssen pharmaceuticals, inc. - acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d), codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j) - acetaminophen 300 mg - tylenol® with codeine (acetaminophen and codeine phosphate) 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. because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses (see warnings ), reserve tylenol® with codeine tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] - have not provided adequate analgesia, or are not expected to provide adequate analgesia, - have not been tolerated, or are not expected to be tolerated. tylenol® with codeine is contraindicated for: - all children younger than 12 years of age (see warnings ). - post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see warnings ). tylenol® with codeine is contraindicated in patients with: - significant respiratory depression (see warnings ). - acute or severe bronchial asthma in an unmonitor

USA - engelsk - NLM (National Library of Medicine)

actavis pharma, inc. - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), butalbital (unii: khs0az4jvk) (butalbital - unii:khs0az4jvk), caffeine (unii: 3g6a5w338e) (caffeine - unii:3g6a5w338e), aspirin (unii: r16co5y76e) (aspirin - unii:r16co5y76e) - codeine phosphate 30 mg - butalbital, aspirin, caffeine, and codeine phosphate capsules, usp  are indicated for the management of the symptom complex of tension (or muscle contraction) headache, when non-opioid analgesic and alternative treatments are inadequate.  limitations of use : because of the risks of addiction, abuse, and misuse with opioids and butalbital, even at recommended doses [see warnings and precautions ( 5.1 )] , reserve butalbital, aspirin, caffeine, and codeine phosphate capsules, usp for use in patients for whom alternative treatment options (e.g., non-opioid, non-barbiturate analgesics): - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia butalbital, aspirin, caffeine, and codeine phosphate capsules, usp are contraindicated for: - all children younger than 12 years of age [see warnings and precautions ( 5.5 )] - postoperative management in children younger than 18 years of age following tonsillectomy and/or adeno