Codeine Use In Children Research Articles

Evaluation of Pupillometry for CYP2D6 Phenotyping in Children Treated with Tramadol.

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol's pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary response and tramadol PK. Our objective was to evaluate pupillometry as a phenotyping method to assess CYP2D6 activity in children treated with tramadol. We included 41 children (mean age 11 years) receiving a first dose of tramadol (2 mg/kg) in the emergency room (ER) as part of their routine care. CYP2D6 phenotyping and genotyping were performed. The concentrations of tramadol and its active metabolite, M1, were measured, and static and dynamic pupillometry was conducted using a handheld pupillometer at the time of tramadol administration and during the ER stay. Pupillometric measurements were obtained for 37 children. Tramadol affected pupillary parameters, with a decrease in pupil diameter in 83.8% of children (p = 0.002) (mean decrease 14.1 ± 16.7%) and a decrease in reflex amplitude constriction in 78.4% (p = 0.011) (mean decrease 17.7 ± 34.5%) at T150 compared to T0. We were unable to identify a correlation between pupillometry measurements and CYP2D6 activity. Likely confounding factors include light intensity, pain, and stress, making the procedure less feasible in paediatric emergency settings.

Relationship Between Severe Respiratory Depression and Codeine-Containing Antitussives in Children: A Nested Case-Control Study.

BackgroundGuidelines recommend against all codeine use in children for its common indications of analgesia and cough suppression because of uncertain benefits and potential risk of death. However, because of its rarity, the occurrence of severe respiratory depression associated with codeine-containing antitussives has been poorly investigated. The objective of this study was to investigate the association between codeine-containing antitussives and severe respiratory depression in children.MethodsWe retrospectively identified Japanese children who were prescribed antitussives for respiratory diseases from a large Japanese administrative claims database (JMDC, Tokyo, Japan). We collected data on baseline characteristics including age, sex, and comorbidity. Each case was matched with four controls with the same sex and age in the same year from the same type of medical institution. We then examined the association between codeine-containing antitussives and subsequent severe respiratory depression using multivariable conditional logistic regression analysis.ResultsOf 164,047 children, 18,210 (11.1%) were prescribed codeine-containing antitussives. Of the children who took codeine-containing drugs, seven experienced severe respiratory depression. After adjusting for confounding factors, there was no significant difference in the proportion of severe respiratory depression between children with and without codeine-containing antitussives (odds ratio 1.15; 95% confidence interval, 0.48–2.78).ConclusionOccurrence of respiratory depression was very rare, and the association of codeine with respiratory depression was insignificant, even in a large sample of children in Japan.

Pharmacist and Pediatrician Knowledge of Codeine Use in Children.

In 2011, approximately 1.7 million pediatric patients had a codeine-containing prescription filled at a US retail pharmacy. Numerous cases involving serious adverse effects or fatalities have been reported in children who have been prescribed codeine. In 2013, the US Food and Drug Administration added a boxed warning to avoid codeine in children after a tonsillectomy. The purpose of this study is to determine pharmacists' and pediatricians' knowledge of the boxed warning for codeine in children. Two separate surveys were administered to community pharmacists in Maryland, pediatricians, and pediatric residents at a single institution in Maryland. Both surveys consisted of questions regarding knowledge of the boxed warning for codeine in children. There was no difference in the awareness of the boxed warning between pharmacists (48.9%, n = 43) and pediatricians (51.3%, n = 41, p = 0.88). More pharmacists knew that ultrarapid metabolizers have the risk for increased adverse events from codeine (39.5% pharmacists vs. 20% pediatricians, p = 0.01). In addition, 36% of pharmacists and 33% of pediatricians noted that it was never appropriate to use codeine in a child (p = 0.73). Only half of pharmacists and pediatricians surveyed were aware of the boxed warning for codeine. One third of pharmacists and pediatricians in this study would never use codeine in a child. Therefore, more education is needed for pharmacists and pediatricians regarding the dangers of using codeine in children.

Pain after tonsillectomy: effectiveness of current guidelines?

Tonsillectomy is one of the most common major surgical procedures performed in children. In 2013, the use of codeine in children was severely restricted. French guidelines for treating tonsillectomy's postoperative pain at home have been reconsidered OBJECTIVE: The aim of our study was to measure effectiveness and safety of two schedules: acetaminophen + ibuprofen (A + I) and acetaminophen + tramadol (A + T) in children who underwent tonsillectomy. We undertook a 1 year prospective and observational single-center study. All children who underwent tonsillectomy were eligible. The choice of the regimen, A + I group or A + T group, was left for the anesthesiologist in charge, done during the pre-anesthetic assessment. After hospital discharge, parents had to give systematically A + I or A + T, 4 times a day during 5days and then acetaminophen alone for the next 5days The primary endpoint was the home pain assessed using Parents' Postoperative Pain Measurement Short Form (PPPM-SF) scale. Secondary endpoints were the rate of further hospitalization and/or surgery due to tonsillectomy-related adverse events. Over the study period, 342 tonsillectomies were performed. The return rate of PPPM-SF scales was 58%. Two hundred patients were analyzed. The median age was 4 [3; 5.2] years and was lower in group A + I (4 [3; 5]; 5 [4; 7]; p < 0.0001). PPPM-SF scores were greater than or equal to 3 in both groups during the first 6 postoperative days. The mean decrease of PPPM-SF score over time was higher in group A + I than in group A + T (p = 0.007). Readmission rate was significantly higher in group A + T (A + I: 0; A + T: 7; p = 0.002) as the rate of reoperation for bleeding (A + I: 0; A + T: 3; p = 0.049). Home pain management after tonsillectomy should be improved. In clinical practice, A + I seems at least as effective as the combination A + T, without increasing readmission and/or additional surgery for bleeding.

Analgesia following adenotonsillar surgery in children: is Oramorph required in addition to paracetamol and ibuprofen?

BackgroundRecent advice against codeine use in children prompted our unit to prescribe Oramorph as required, in addition to regular paracetamol and ibuprofen, as post-(adeno)tonsillectomy analgesia. This study investigated whether Oramorph was in fact required. MethodsFollowing (adeno)tonsillectomy, parents were telephoned and asked whether they used Oramorph. ResultsOf 56 children studied, 41 (73.2%) were given Oramorph. In the 15 (26.8%) that were not, this was because parents felt it was not required in 14 children, and in 1 case, it was due to worries about side effects. Overall, 14 carers (25.0%) expressed concerns about Oramorph use, mostly over possible side effects. ConclusionWhen regular paracetamol and ibuprofen are used post-(adeno)tonsillectomy, nearly three quarters of children require Oramorph as well. Prescribing Oramorph as required, in addition to regular paracetamol and ibuprofen, is appropriate following adenotonsillar surgery.

Codeine use among children in the United States: a nationally representative study from 1996 to 2013.

Concerns regarding the safety of codeine have been raised. Cases of life-threatening respiratory depression and death in children have been attributed to codeine's polymorphic metabolic pathway. International health agencies recommend restricted use of codeine in children. Despite these recommendations, the epidemiology of codeine use among children remains unknown. Our objective was to examine patterns of codeine use in the US among children. A cross-sectional analysis of children of age 0-17 years from 1996 to 2013 in the US was performed. Data were extracted from MEPS, a nationally representative set of health care surveys. Prevalence rates of codeine use between 1996 and 2013 were examined. Multivariable logistic regression examined relationships between codeine use and patient demographics. Codeine use remained largely unchanged from 1996 to 2013 (1.08 vs 1.03 million children, respectively). Odds of codeine use was higher in ages 12-17 (OR, 1.40; [1.21-1.61]), outside of the Northeastern US, and among those with poor physical health status (OR, 3.29 [1.79-6.03]). Codeine use was lower in children whose ethnicity was not white and those uninsured (OR, 0.47 [0.34-0.63]). Codeine was most frequently prescribed by emergency physicians (18%) and dentists (14%). The most common condition associated with codeine use was trauma-related pain. Pediatric codeine use has declined since 1996; however, more than 1 million children still used codeine in 2013. Health care providers must be made aware of guidelines advising against the use of codeine in children. Codeine is potentially hazardous and safer alternatives to treat children's pain are available.

CHANGING PRESCRIBING CULTURE – A FOCUS ON CODEINE POSTPARTUM

AimTo eliminate the prescribing of codeine and codeine combination products postpartum to improve safety in breast fed infants.Concerns have been raised over the use of codeine and codeine combination products...

A new analgesia regimen after (adeno) tonsillectomy in children: a pilot study

The objective was to ascertain the efficacy of a new analgesic regimen introduced in children undergoing (adeno)tonsillectomy in view of the ban on codeine use in children <12 years by the European Medicines Agency (EMA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA). Prospective pilot study at a paediatric tertiary referral centre. A total of 176 children undergoing (adeno) tonsillectomy over a 5-month period (Sept 2013-Jan 2014) were included in the study. Data were prospectively collected on analgesia used peri-operatively and patients were discharged on regular paracetamol and ibuprofen for 7 days and three doses of oral morphine sulphate solution to be used on days 3, 4 and 5. Pain scores were recorded on days 1-10 post-operatively using the Wong Baker Faces Pain Rating scale. The pain scores were significantly better (P-value < 0.0001) in children who were compliant with morphine (n = 93) than those who were not (n = 32). We also found that children who were compliant with morphine were less likely to seek help out of hours (P-value < 0.001). Oral morphine sulphate solution provides a reasonable alternative to codeine, albeit one should bear in mind that parental concerns and adverse effects of the drug were seen in a minority of patients (n = 11) and anaesthetists were reluctant to prescribe the drug in cases of severe OSA or associated central apnoeas (n = 7).

Pain management in the acute care setting: Update and debates.

Pain management in the paediatric acute care setting is underutilised and can be improved. An awareness of the analgesic options available and their limitations is an important starting point. This article describes the evolving understanding of relevant pharmacogenomics and safety data of the various analgesic agents with a focus on agents available in Australia and New Zealand. It highlights the concerns with the use of codeine in children and discusses alternative oral opioids. Key features of oral, parenteral, inhaled and intranasal analgesic agents are discussed, as well as evidence supported use of sweet tasting solutions and non-pharmacological interventions. One of the biggest changes in acute care pain management has been the advent of intranasal fentanyl providing reliable potent analgesia without the need for intravenous access. The article will also address the issue of multimodal analgesia where a single agent is insufficient.

DTB Select: 6 | June 2015

Further restrictions on the use of codeine in children ● MHRA reminder on misleading medicine advertising ● A protocol for deprescribing ● Regulating herbal medicines: next steps ● Paracetamol ineffective...

WHAT DO DOCTORS WORKING IN PAEDIATRICS THINK ABOUT SWITCHING FROM CODEINE TO MORPHINE?

Purpose Following the publication of restrictions on the use of codeine in children by the Medicines and Healthcare Products Regulatory Agency (MHRA) in July 2013,1 many paediatric centres changed to using morphine in place of codeine. In our centre, the switch occurred in October 2013. Approximately six weeks later we asked all doctors working in paediatrics for their opinions on switching from codeine to morphine. Methods Six questions were developed to assess how doctors had found out about the safety concerns with codeine; their opinion on the information provided and the coordination of the switch within the Trust; whether they thought the switch to morphine was a positive or negative change and what they thought could be done to improve the way morphine is used. The questions were inputted into survey monkey software and the link generated was emailed to all consultants and junior doctors working in paediatrics (approximately 280 recipients). Two weeks after the survey was circulated the responses were collated and analysed using descriptive statistics and thematic analysis. Results Twenty nine doctors responded to the survey. They reported receiving information about the safety concerns with codeine from a variety of sources with emails from MHRA/outside the Trust being the most common. 83% were happy with the information they received from within the Trust about the planned switch from codeine to morphine and 88% were positive or neutral about how the switch was coordinated. Of the 64 comments made about using morphine instead of codeine, 77% were negative, 20% positive and 3% neutral with the most common concerns being increased risk of errors, abuse/ingestion potential in the community, lack of an intermediate analgesic and reduced availability due to controlled drug restrictions. Positive themes included improved pain management with morphine, simpler regimes and the variety of preparations giving greater flexibility. Ideas for improving the way morphine is used included audit, feedback, training and using a single strength of morphine solution or adding warnings to highlight the stronger preparation. Conclusions Although the response rate to the survey was poor, the results showed that the majority of those replying had negative opinions about the switch to using morphine instead of codeine. Most were concerned about the potential risks associated with increased use of morphine although there were positive comments about morphine improving pain management. The survey is due to be repeated in July 2014 to determine whether opinions have changed and a comparison between the quantities of morphine and codeine issued from pharmacy will be undertaken to see if overall oral opiate use has changed.

Tramadol can selectively manage moderate pain in children following European advice limiting codeine use.

The European Medicine Agency recommendations limiting codeine use in children have created a void in managing moderate pain. We review the evidence on the pharmacokinetic, pharmacodynamic and safety profile of tramadol, a possible substitute for codeine. Tramadol appears to be safe in both paediatric inpatients and outpatients. It may be appropriate to limit the current use of tramadol to monitored settings in children with risk factors for respiratory depression, subject to further safety evidence.

Why Can’t We Retire Codeine?

Some remedies have long outlived their usefulness and have thankfully been relegated to historical archives, supplanted by safer, more effective drugs. We no longer prescribe mercury loop diuretics or antisyphilitic arsenicals. Yet, the use of codeine-containing products persists for cough relief and analgesia in children. As Kaiser et al1 report in their study “National Patterns of Codeine Prescriptions for Children in the Emergency Department” in this month’s issue, prescriptions for codeine-containing products barely edged down in frequency between 2001 and 2010, despite convincing studies documenting their lack of benefit and serious adverse effects. Using data from the National Hospital and Ambulatory Medical Care Survey database, they found codeine prescribed in the pediatric emergency department at the incredible rate of 558 805 to 876 729 prescriptions per year with only a small statistical decline over that period. Additionally, the US Food and Drug Administration reported that >1.7 million children aged 17 years and younger had a prescription for a codeine product filled at a pharmacy in 2011.2 These high numbers continue despite guidance from professional societies discouraging the use of codeine in children. Why do pediatric practitioners continue to write prescriptions for codeine? Kaiser et al … Address correspondence to Alan D. Woolf, MD, MPH, FAAP, Pediatric Environmental Health Center, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: alan.woolf{at}childrens.harvard.edu

National patterns of codeine prescriptions for children in the emergency department.

National guidelines have recommended against codeine use in children, but little is known about prescribing patterns in the United States. Our objectives were to assess changes over time in pediatric codeine prescription rates in emergency departments nationally and to determine factors associated with codeine prescription. We performed a serial cross-sectional analysis (2001-2010) of emergency department visits for patients ages 3 to 17 years in the nationally representative National Hospital Ambulatory Medical Care Survey. We determined survey-weighted annual rates of codeine prescriptions and tested for linear trends over time. We used multivariate logistic regression to identify characteristics associated with codeine prescription and interrupted time-series analysis to assess changes in prescriptions for upper respiratory infection (URI) or cough associated with two 2006 national guidelines recommending against its use for these indications. The proportion of visits (N = 189 million) with codeine prescription decreased from 3.7% to 2.9% during the study period (P = .008). Odds of codeine prescription were higher for children ages 8 to 12 years (odds ratio [OR], 1.42; 95% confidence interval [1.21-1.67]) and among providers outside the northeast. Odds were lower for children who were non-Hispanic black (OR, 0.67 [0.56-0.8]) or with Medicaid (OR, 0.84 [0.71-0.98]). The 2006 guidelines were not associated with a decline in codeine prescriptions for cough or URI visits. Although there was a small decline in codeine prescription over 10 years, use for cough or URI did not decline after national guidelines recommending against its use. More effective interventions are needed to prevent codeine prescription to children.

PRAC recommends restricting codeine use in children

PRAC recommends restricting codeine use in children

Wither codeine?

Wither codeine?

Post-op codeine use in children, new Boxed Warning

Post-op codeine use in children, new Boxed Warning

Pain Management in Children: Part 2 — A Transition from Codeine to Morphine for Moderate to Severe Pain in Children

Opioids remain the agent of choice for the treatment of moderate to severe pain in both adults and children. Codeine, an opioid analogue, is commonly used in the treatment of mild to moderate pain in both adults and children. However, there has been growing concern about the safety of codeine use in children. This second part of the article on pain management in children will focus on codeine's questionable efficacy and safety concerns about the use of codeine in children.

Pain Management in Children: Part 1 — Pain Assessment Tools and a Brief Review of Nonpharmacological and Pharmacological Treatment Options

If pain is not treated quickly and effectively in children, it can cause long-term physical and psychological sequelae. Therefore, it is important for all health care providers to understand the importance of effective pain control in children. This article is divided into 2 parts: Part 1 reviews the pharmacotherapy of pain management in children and Part 2 will review the problems relating to the use of codeine in children, and the rationale for recommending morphine as the opioid of choice in the treatment of moderate to severe pain. There has been growing concern about codeine's lack of efficacy and increased safety concerns in its use in children. Due to the variability of codeine metabolism and unpredictable effects on efficacy and safety, The Hospital for Sick Children in Toronto, Ontario, no longer includes codeine or codeine-containing products on the regular hospital formulary and now recommends oral morphine as the agent of choice for the treatment of moderate to severe pain in children. A knowledge translation (KT) strategy was developed and implemented by the hospital's Pain Task Force to support this practice change.