CORRESPONDENCE: LETTERS
70
Correspondence
Response to Magos et al. 22 January 2014
Sir, In their correspondence, Magos et al. make a number of relevant points that will resonate with those ENT surgeons and paediatric anaesthetists in the UK who manage children during and after tonsillectomy.1 Regarding the reference group of children with OSA, and the regular post-operative codeine regimen prescribed, their points are well made suggesting a blanket ban on any child receiving codeine as rescue analgesia after tonsillectomy for all indications might be a disproportionate reaction from the medicines safety authorities in both Europe and USA. I share the view of Magos et al.1 that the lack of specific alternative guidance form MHRA is unhelpful. I am sure we anticipate UK professional organisations, including ENT-UK and APA (Association of Paediatric Anaesthetists), making representations to MHRA to clarify the need to ban the use of codeine in all children; if this is to be their final decision, what safe alternatives MHRA propose. My own current practice is similar to that of the authors, which at the current time is a pragmatic modification in practice to manage postoperative pain in these children. I do not, however, believe that tramadol suspension might be a safe, suitable alternative to oral codeine. In the UK, tramadol is not licensed for use in children less than 12 years of age. While many adult drugs are used for children, there are other significant pharmacological and safety considerations with tramadol. Like codeine, tramadol is a pro-drug, metabolised to O-desmethyltramadol, a potent, relatively selective agonist of l-opioid receptors. The complex analgesic action of tramadol results from the above effect, plus the selective reuptake inhibition of both serotonin and noradrenaline. Tramadol suffers from the same polymorphism as codeine in its metabolism, sharing the some of the same cytochrome P450 isoenzymes, (including CYP2D6), with the associated risks of respiratory depression.2 Due to the
polymorphism of these enzymes, metabolism of tramadol can vary 14-fold between individuals.3 The drug has also been the subject of FDA warnings in regard to toxicity.4 Between 2006 and 2011, the UK Advisory Council on the Misuse of Drugs (ACMD) reported 60 fatalities attributed to tramadol, in contrast to seven for codeine.5 Until such time that MHRA reviews and reconsiders its guidance, limited supply of oral morphine solution, used as rescue analgesia or in planned, limited doses, in addition to regular paracetamol and ibuprofen is probably the safest option. For those children in whom ibuprofen is contraindicated, a small, more regular dose of oral morphine might be appropriate. Conflict of interests
None to declare. Robb, P.J. Consultant ENT Surgeon, Epsom & St Helier University Hospitals NHS Trust, Epsom, UK E-mail: [email protected]
References 1 Magos T.A., Syed M.I. & Montague M.-L. (2014) Re: more codeine fatalities after tonsillectomy in North American children. Time to revise prescribing practice. Clin. Otolaryngol. 39, 69 2 Stamer U., Stuber F., Muders T. & Musshoff F. (2008) Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 107, 926–929 3 Halling J., Weihe P. & Brosen K. (2008) CYP2D6 polymorphism in relation to tramadol metabolism: a study of Faroese patients. Ther. Drug Monit. 30, 271–275 4 www.fda.gov/downloads/safety/medication/…/UCM213265.pdf [accessed on 11 January 2014] 5 www.gov.uk/government/publications/acmd-advice-on-tramadol/ [accessed on 11 January 2014]
© 2014 John Wiley & Sons Ltd Clinical Otolaryngology 39, 67–75
70
Correspondence
Response to Magos et al. 22 January 2014
Sir, In their correspondence, Magos et al. make a number of relevant points that will resonate with those ENT surgeons and paediatric anaesthetists in the UK who manage children during and after tonsillectomy.1 Regarding the reference group of children with OSA, and the regular post-operative codeine regimen prescribed, their points are well made suggesting a blanket ban on any child receiving codeine as rescue analgesia after tonsillectomy for all indications might be a disproportionate reaction from the medicines safety authorities in both Europe and USA. I share the view of Magos et al.1 that the lack of specific alternative guidance form MHRA is unhelpful. I am sure we anticipate UK professional organisations, including ENT-UK and APA (Association of Paediatric Anaesthetists), making representations to MHRA to clarify the need to ban the use of codeine in all children; if this is to be their final decision, what safe alternatives MHRA propose. My own current practice is similar to that of the authors, which at the current time is a pragmatic modification in practice to manage postoperative pain in these children. I do not, however, believe that tramadol suspension might be a safe, suitable alternative to oral codeine. In the UK, tramadol is not licensed for use in children less than 12 years of age. While many adult drugs are used for children, there are other significant pharmacological and safety considerations with tramadol. Like codeine, tramadol is a pro-drug, metabolised to O-desmethyltramadol, a potent, relatively selective agonist of l-opioid receptors. The complex analgesic action of tramadol results from the above effect, plus the selective reuptake inhibition of both serotonin and noradrenaline. Tramadol suffers from the same polymorphism as codeine in its metabolism, sharing the some of the same cytochrome P450 isoenzymes, (including CYP2D6), with the associated risks of respiratory depression.2 Due to the
polymorphism of these enzymes, metabolism of tramadol can vary 14-fold between individuals.3 The drug has also been the subject of FDA warnings in regard to toxicity.4 Between 2006 and 2011, the UK Advisory Council on the Misuse of Drugs (ACMD) reported 60 fatalities attributed to tramadol, in contrast to seven for codeine.5 Until such time that MHRA reviews and reconsiders its guidance, limited supply of oral morphine solution, used as rescue analgesia or in planned, limited doses, in addition to regular paracetamol and ibuprofen is probably the safest option. For those children in whom ibuprofen is contraindicated, a small, more regular dose of oral morphine might be appropriate. Conflict of interests
None to declare. Robb, P.J. Consultant ENT Surgeon, Epsom & St Helier University Hospitals NHS Trust, Epsom, UK E-mail: [email protected]
References 1 Magos T.A., Syed M.I. & Montague M.-L. (2014) Re: more codeine fatalities after tonsillectomy in North American children. Time to revise prescribing practice. Clin. Otolaryngol. 39, 69 2 Stamer U., Stuber F., Muders T. & Musshoff F. (2008) Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 107, 926–929 3 Halling J., Weihe P. & Brosen K. (2008) CYP2D6 polymorphism in relation to tramadol metabolism: a study of Faroese patients. Ther. Drug Monit. 30, 271–275 4 www.fda.gov/downloads/safety/medication/…/UCM213265.pdf [accessed on 11 January 2014] 5 www.gov.uk/government/publications/acmd-advice-on-tramadol/ [accessed on 11 January 2014]
© 2014 John Wiley & Sons Ltd Clinical Otolaryngology 39, 67–75
