ארצות הברית - אנגלית - 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

ארצות הברית - אנגלית - NLM (National Library of Medicine)

mainpointe pharmaceuticals - codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j), chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u) - tuxarin er is indicated for the temporary relief of cough and upper respiratory symptoms 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 population (8.4)]. - contraindicated in pediatric patients under 12 years of age [see contraindications (4), use in specific populations (8.4) ]. - contraindicated in pediatric patients 12 to 18 years of age after tonsillectomy or adenoidectomy [see contraindications (4), 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 tuxarin er 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. tuxarin er is contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.2, 5.3, 5.4), use in specific populations (8.4) ]. - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions (5.2, 5.3)]. tuxarin er 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 (5.5) ]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.10) ]. - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within 14 days [see warnings and precautions (5.13), drug interactions (7.7) ]. - hypersensitivity to codeine, chlorpheniramine, or any of the inactive ingredients in tuxarin er [see adverse reactions (6) ]. persons known to be hypersensitive to certain other opioids may exhibit cross-reactivity to codeine. risk summary tuxarin er 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 (5.15) and clinical considerations ]. there are no available data with tuxarin er 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 tuxarin er; 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 15 times the maximum recommended human dose (mrhd) in the presence of maternal toxicity (see data ). chlorpheniramine administered by the oral route to mice throughout pregnancy was embryolethal at a dose approximately 9 times the mrhd and decreased postnatal survival when dosing was continued after parturition. chlorpheniramine administered by the oral route to male and female rats prior to mating produced embryolethality at a dose approximately 9 times the mrhd (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 (5.15) ]. 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 tuxarin er, 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 no new primary pharmacodynamic studies were conducted. codeine is a well-established antitussive and chlorpheniramine maleate is a recognized antihistamine. both drugs have been used at these strengths in combination for several years. codeine 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. 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. chlorpheniramine the majority of studies examining the use of chlorpheniramine in pregnancy did not find an association with an increased risk of congenital anomalies. in the few studies reporting an association, there was no consistent pattern of malformations noted. animal data reproductive toxicity studies have not been conducted with tuxarin er; 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 15 times the mrhd (on a mg/m2 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 7 and 35 times, respectively, the mrhd (on a mg/m2 basis with maternal oral doses of 30 mg/kg/day in rabbits and 600 mg/kg/day in mice). chlorpheniramine in embryofetal development studies with pregnant rats and rabbits dosed throughout the period of organogenesis, chlorpheniramine produced no adverse developmental effects at oral doses up to approximately 35 and 45 times, respectively, the mrhd on a mg/m2 basis. however, in a reproduction study with pregnant mice dosed throughout pregnancy, chlorpheniramine produced embryolethality at a dose approximately 9 times the mrhd (on a mg/m2 basis with a maternal oral dose of 20 mg/kg/day) and decreased postnatal survival when dosing was continued after parturition. in a fertility and reproduction study with male and female rats dosed prior to mating, chlorpheniramine produced embryolethality at a dose approximately 9 times the mrhd (on a mg/m2 basis with an oral parental dose of 10 mg/kg/day). 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 tuxarin er [see warnings and precautions (5.3) ]. there are no data on the presence of tuxarin er in human milk, the effects of tuxarin er on the breastfed infant, or the effects of tuxarin er on milk production; however, data are available with codeine and chlorpheniramine. 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. chlorpheniramine chlorpheniramine is present in human milk. chlorpheniramine has not been reported to cause effects on the breastfed infant. the published literature suggests that chlorpheniramine may decrease milk production based on its anticholinergic effects. (see clinical considerations ) clinical considerations infants exposed to tuxarin er 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 tuxarin er, may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6), clinical pharmacology (12.2) ]. tuxarin er 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), warnings and precautions (5.4) ]. 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 (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: - tuxarin er is contraindicated in all children younger than 12 years of age [see contraindications (4)] . - tuxarin er 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 tuxarin er 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)] . clinical studies have not been conducted with tuxarin er in geriatric populations. use caution when considering the use of tuxarin er 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 (5.5) ]. respiratory depression is the chief risk for elderly patients treated with opioids, including tuxarin er. 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 (5.5, 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, monitor these patients closely for respiratory depression, sedation, and hypotension. the pharmacokinetics of tuxarin er 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. chlorpheniramine is cleared substantially by the kidney. as such, impaired renal function could potentially lead to the risk of decreased clearance and thereby increased retention or systemic levels of chlorpheniramine. therefore, tuxarin er should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for signs of hydrocodone toxicity (respiratory depression, sedation, and hypotension) and chlorpheniramine toxicity. no formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of tuxarin er in this patient population are unknown. chlorpheniramine is extensively metabolized by liver before elimination from the body. as such, impaired hepatic function could potentially lead to the risk of decreased metabolism and thereby increased systemic levels of chlorpheniramine. therefore, tuxarin er should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for signs of hydrocodone toxicity (respiratory depression, sedation, and hypotension) and chlorpheniramine toxicity. tuxarin er contains codeine, a schedule iii controlled substance. codeine tuxarin er contains codeine, a substance with a high potential for abuse similar to other opioids including morphine and codeine. tuxarin er 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. tuxarin er, 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 tuxarin er tuxarin er is for oral use only. abuse of tuxarin er poses a risk of overdose and death. the risk is increased with concurrent use of tuxarin er with alcohol and other central nervous system depressants [see warnings and precautions (5.9) ]. 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, tuxarin er 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), 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 tuxarin er 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 (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., 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) ].

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 2 mg in 5 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 2 mg in 10 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

magna pharmaceuticals, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine anhydrous - unii:ux6owy2v7j) - chlorpheniramine maleate 2 mg in 5 ml - antihistamine antitussive (cough suppressant) temporarily relieves these symptoms due to the common cold, hay fever (allergic rhinitis) or other upper respiratory allergies: - runny nose - sneezing - itching of the nose or throat - itchy, watery eyes - cough due to minor throat and minor bronchial irritation stop use and ask a doctor if - cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache. a persistent cough may be a sign of a serious condition - may cause or aggravate constipation

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 0.999 mg in 4.5 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 1.995 mg in 7.5 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 1.001 mg in 3.5 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

codadose, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 0.999 mg in 3 ml - temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you go to sleep; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies warnings in children who have chronic pulmonary disease, shortness of breath, or who are taking other drugs unless directed by a doctor; for persistent or chronic cough such as occurs with asthma or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache.  these could be signs of a serious condition.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

respa pharmaceuticals, inc. - chlorpheniramine maleate (unii: v1q0o9oj9z) (chlorpheniramine - unii:3u6io1965u), codeine phosphate (unii: gsl05y1mn6) (codeine - unii:q830pw7520) - chlorpheniramine maleate 2 mg in 5 ml - - a persistent or chronic cough such as occurs with smoking, asthma or emphysema - a cough that occurs with too much phlegm (mucus) - a chronic pulmonary disease, shortness of breath, or children who are taking other drugs - a breathing problem such as emphysema or chronic bronchitis, or if you have glaucoma - difficulty in urination due to enlargement of the prostate gland. - cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash or persistent headache; these could be signs of a serious condition. - may cause or aggravate constipation.