Abstract
Codeine is a mild opioid widely used as an analgesic in various age groups, including various pediatric settings. It is a prodrug that owes its analgesic effect almost entirely to the principal metabolite: morphine. The genetic polymorphisms can contribute to making the pharmacokinetics of codeine hard to predict and this it is particularly important in the pediatric population because infants and children have greater susceptibility to the side-effects of morphine. In recent years there have been several reports in the literature on the risks relating to the use of codeine. In August 2012, the American Food and Drugs Administration began to revise its recommendations for the safe use of codeine and in February 2013, established that codeine should not be used for postoperative pain control in children undergoing adenoidectomy and/or tonsillectomy and did restrict the use of this drug in the pediatric population. In June 2013, the European Medicine Agency opted the same decision. In July 2013, the Agenzia Italiana del Farmaco prohibit the use of medicines containing codeine for patients under 12 years old and recommended a limited use of the drug, in many other situations. Complying with these recommendations naturally means changing habits and treatment strategies well established in pediatric practice, but other drugs, tools and techniques available enable us to continue to assure an adequate pain control in pediatric patients, irrespective of their age and situation. The article proposes same alternatives of pain control drugs.
Highlights
In recent years there have been several reports in the literature on the risks relating to the use of codeine.In 2007 Madadi [3] reported on the death of a newborn breastfed by a mother who had been given codeine to control postpartum pain
Codeine is a mild opioid widely used as an analgesic in various age groups, including various pediatric settings
Since it is impossible to identify children who are ultra-rapid metabolizers of codeine in advance, and given the correlated risks, the Food and Drugs Administration (FDA) established that codeine should not be used for postoperative pain control in children undergoing adenoidectomy and/or tonsillectomy
Summary
Codeine is a mild opioid widely used as an analgesic in various age groups, including various pediatric settings. The enzyme is more active in some individuals (termed ultra-rapid metabolizers), converting codeine into morphine more quickly and completely This means that, after they have been administered the right dose of the drug for their ideal weight and age, these individuals have higher blood levels of morphine than controls. Like the polymorphism of cytochrome 450 isoenzyme CYP2D6, other genetic polymorphisms can contribute to making the pharmacokinetics of codeine hard to predict (including variations in morphine metabolism, its passage through the blood–brain barrier, and different receptor kinetics) All these genetic variations can have clinical consequences, and an unfortunate combination of different polymorphisms can give rise to toxic levels of morphine - even after an appropriate dose of codeine has been administered - with a higher risk of side-effects. This is important in the pediatric population because the fact of being newborn or an infant is associated per se with a greater susceptibility to the side-effects of morphine [1,2]
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