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Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing). This rapid conversion results in higher than expected serum morphine levels. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. Data are not available for other ethnic groups. The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (gene duplications denoted as *1/*1xN or *1/*2xN). Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine. Death Related to Ultra-Rapid Metabolism of Codeine to Morphine: Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and 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).
#Cod 3 tablet skin#
Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Serious skin reactions: Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.
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Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well. Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. At therapeutic doses, the analgesic effect reaches a peak within 2 hours and persists between 4 and 6 hours. The remainder of the dose is excreted in the feces.
#Cod 3 tablet free#
The urinary secretion products consist of free and glucuronide conjugated codeine (about 70%), free and conjugated norcodeine (about 10%), free and conjugated morphine (about 10%), normorphine (4%), and hydrocodone (1%). The elimination of codeine is primarily via the kidneys, and about 90% of an oral dose is excreted by the kidneys within 24 hours of dosing. The plasma concentration does not correlate with brain concentration or relief of pain however, codeine is not bound to plasma proteins and does not accumulate in body tissues. Codeine crosses the blood-brain barrier, and is found in fetal tissue and breast milk. It is rapidly distributed from the intravascular spaces to the various body tissues, with preferential uptake by parenchymatous organs such as the liver, spleen and kidney. Codeine: Codeine is readily absorbed from the gastrointestinal tract. Pharmacokinetics: The behavior on the individual components is described below. This product combines the analgesic effects of a centrally acting analgesic, codeine, with a peripherally acting analgesic, acetaminophen.