|The capsules contain sodium metabisulfite, a sulfite that may cause allergic reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than non-asthmatic people.These capsules should be used with caution in patients with head injuries, increased intracranial pressure, acute abdominal conditions, the elderly and debilitated, and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease and prostatic hypertrophy or urethral stricture, myasthenia gravis, biliary tract disorders (including recent biliary tract surgery) , pre-existing respiratory depression or those with the potential to develop respiratory depression e.g. pulmonary emphysema, known ultra-rapid metabolisers of codeine, reduced blood volume, seizures, shock, ulcerative colitis.The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.Severe liver damage may occur if the maximal daily dose is exceeded, if Tylex is taken together with another paracetamol-containing product, or if Tylex is taken while consuming large amounts of alcohol. Although paracetamol might logically be presumed to be the best alternative analgesic in patients with aspirin sensitivity, cross reactions have been reported.CYP2D6 metabolismCodeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels. General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal.Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:|
||3.4% to 6.5%
||1.2% to 2%
||3.6% to 6.5%
Post-operative use in childrenThere have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultrarapid or extensive metabolisers in their ability to metabolise codeine to morphine.
Children with compromised respiratory functionCodeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.At high doses codeine has most of the disadvantages of morphine, including respiratory depression. Codeine can produce drug dependence of the morphine type, and therefore has the potential for being abused. Prolonged regular use, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped. Codeine may impair the mental/or physical abilities required for the performance of potentially hazardous tasks.Abrupt withdrawal of opioids from persons physically dependent on them precipitates a withdrawal syndrome, the severity of which depends on the individual, the drug used, the size and frequency of the dose, and the duration of drug use.Patients should be advised that immediate medical advice should be sought in the event of an overdose, because of the risk of delayed, serious liver damage. They should be advised not to exceed the recommended dose, not to take other paracetamol-containing products concurrently, to consult their doctor if symptoms persist and to keep the product out of the reach of children.The long term use of high doses of combined codeine paracetamol has been associated with the occurrence of deafness.