title: Transdermal fentanyl in childhood and adolescence: a comprehensive literature review.
abstract: The recently introduced fentanyl transdermal therapeutic system (TTS) with a drug release rate of 12.5 microg/h matches the lower dosing requirements of cancer pain control in children. It is likely that fentanyl TTS will be used in pediatrics with increasing frequency. We compiled the published evidence on pediatric applications of this drug formulation to help physicians get the most benefit from its use. Within this systematic review, a total of 11 observational clinical or pharmacokinetic studies were identified. There are no pediatric randomized or controlled cohort studies. Pharmacokinetic studies poorly described time-concentration profiles after application. The time to reach steady-state serum drug concentrations seems to be longer, clearance (expressed as liters per kilogram per hour) higher, and elimination half-life shorter in children than in adults. There are no fundamental differences in effect or profile of adverse effects compared with adults. Fentanyl TTS may be associated with less constipation compared with morphine use. Frequently, pediatric patients need supplemental mechanical fixation of the fentanyl TTS by means of medical tape. Younger patients tend to have a higher fentanyl requirement when referenced to body weight. Both parents and medical professionals are satisfied with fentanyl TTS to a higher degree than with individual analgesic pretreatment regimens. Fentanyl TTS is a promising option for chronic pain control in children. An approximate conversion factor of 45 mg/day oral morphine to 12.5 microg/h fentanyl TTS is used for initial therapy dose estimation in children receiving long-term morphine therapy. This is conservatively low to avoid respiratory depression. Daily oral morphine equivalent dose should be at least 30 mg/d before fentanyl TTS therapy is started with 12.5 microg/h. Evidence for superiority of fentanyl TTS treatment above conventional opioid administration is both scarce and of low quality.
  
  
  CONCLUSIONS
  The article gives a comprehensive overview of all pediatric data concerning the fentanyl TTS. Children may take longer to reach steady-state fentanyl serum concentrations than adults, and younger children may require higher doses referenced to body weight than older children or adults. Consequently, there is a need to provide sufficient medication in the phase of therapy initiation to prevent breakthrough pain. The 72-hour dosing schedule recommended by the manufacturers may not be applicable to children because of poor patch adhesiveness. The authors suggest to ensure firm fixation of the fentanyl TTS with additional medical tape if necessary and to change the fentanyl TTS after 48 hours. Transdermal fentanyl in children may exhibit fewer side effects when compared with other opioids, especially constipation. Randomized studies are urgently needed to definitively answer this question.
authors.affiliation: Vodafone Foundation Institute for Children's Pain Therapy and Pediatric Palliative Care, Children's Hospital, Witten/Herdecke University, Datteln, Germany. boris.zernikow@t-online.de
authors.forename: Boris
authors.initials: B
authors.lastname: Zernikow
authors.forename: Erik
authors.initials: E
authors.lastname: Michel
authors.forename: Brian
authors.initials: B
authors.lastname: Anderson
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D002648:Child; D016503:Drug Delivery Systems; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D009294:Narcotics / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy*; D010372:Pediatrics
chemical_list: D009294:Narcotics; D005283:Fentanyl