Codeine Prescription Research Articles

Risk of overdose and death following codeine prescription among immigrants

BackgroundImmigrants may be at a higher risk of adverse drug reactions, in that poor language proficiency reduces individuals understanding of drug label instructions. Additionally, there are reports of severe or...

Codeine Still Prescribed for Children in the ED

Children presenting to U.S. emergency departments (EDs) with cold and upper respiratory infections are still receiving prescriptions for codeine,

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.

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 Patterns of Codeine Prescriptions for Children in the Emergency Department

Current Practices Regarding Codeine Administration Among Pediatricians and Pediatric Subspecialists

Pharmacogenomic studies have revealed a wide variation in the metabolism of codeine to its active metabolite, morphine. A particular subset of patients, known as ultrarapid metabolizers, possesses multiple copies of the CYP2D6 gene responsible for codeine metabolism. This has been linked to serious morbidity and mortality in pediatric patients leading to considerable debate regarding the use of codeine for analgesia in the pediatric population. The current study surveyed the current practice of codeine prescription in pediatric health care providers from a single tertiary care pediatric hospital. Of the 298 responders, 43.3% (129 of 298) continue to prescribe codeine for pain management in children. The vast majority of codeine prescribers were primary health care providers (89.1%). Most of the primary care practitioners were in office-based (42.6%) or hospital-based (45.7%) group practices. There was no significant difference in codeine use based on years of experience. Given the risks associated with this practice, increased education targeting this group appears warranted.

Boxed Warning Added To-Codeine's Label

* Codeine's prescribing label now carries a boxed warning that the risks of serious respiratory adverse effects and death are increased if the drug is given to children for pain after tonsillectomy or adenoidectomy

Prescription Patterns of Pain Medicine Physicians

Our study surveyed physician members of 3 American pain societies to determine prescription patterns and whether these practices reflect current expert opinion. We sent 3 mailings to 2938 physicians from January 2010 to January 2011. The questionnaire contained 49 questions on topics related to opioids, antidepressants, anticonvulsants, and preferences for the different pain syndromes. A total of 474 physicians responded, representing a 16% return. Seventy-two percent ask patients to sign an opioid agreement, 59% order random urine drug testing, 13% wait until the dose of methadone is between 100 and 150mg before converting the drug to another opioid, and 85% do not think there is a maximum dose of opioids with respect to driving. Most responders prescribe codeine to Caucasians and Asians. While 42% stated that the maximum daily dose of acetaminophen is 3000mg, 75% would decrease the dose in patients who are moderate or heavy drinkers. Fifty-four percent do not order an ECG at all when prescribing tricyclic antidepressants. The responses pertaining to opioid agreements, urine drug testing, acetaminophen, and treatment for neuropathic pain are reassuring in that they prevent misuse and abuse of opioids, prevent acetaminophen-induced hepatotoxicity, and reflect evidence-based treatments. However, we identified gaps in knowledge, including the prescription of codeine in certain populations and the use of electrocardiogram in patients on antidepressants. Further education of physicians who treat chronic pain pharmacologically is warranted.

Mastocytose bulleuse diffuse du nourrisson : une forme clinique rare

Mastocytosis is a rare condition related to an abnormal proliferation of mast cells and their accumulation in tissues. Cutaneous mastocytosis is the most common form and mainly affects newborns and infants. The symptoms are caused by the release of mediators contained in mast cells, including histamine. Mastocytosis may be associated with a mutation in the gene encoding the c-kit receptor. Clinically, there are different dermatological findings, which combine acute cutaneous, digestive, or even hemodynamic manifestations in varying degrees. The diagnosis is confirmed by the histological study of a skin sample. We report here the case of a 4-month-old infant suffering from diffuse cutaneous bullous mastocytosis, a very rare variety of mastocytosis. This infant had an erosive and bullous manifestation of dermatosis, initially confused with impetigo. The proliferation of bullous lesions led to her hospitalization. Codeine intake for pain was responsible for a large and extensive bullous reaction associated with anaphylactic shock. This context of bullous spread occurring after taking codeine led to the suspicion of bullous diffuse cutaneous mastocytosis, a diagnosis that was confirmed histologically. This observation demonstrates the difficulty of mastocytosis diagnosis, mostly due to its rarity, especially in its diffuse bullous forms. The rapid deterioration of this patient, after the codeine prescription, emphasizes the importance of the eviction of histamine-releaser compounds in the management of this disease.

Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: A retrospective cohort study

Objectives. To examine whether postpartum maternal prescription of codeine was associated with an increased risk of harm to newborns. Design. Population-based retrospective cohort study. Setting. Ontario, Canada, from April 1, 1998 to March 1, 2008. Participants. A total of 7804 mothers with publically-funded prescription drug coverage. Women who received a prescription for a codeine-containing product within 7 days following hospital discharge and their neonates were matched to 7804 mothers who did not receive codeine following delivery. Main outcome measures. The primary outcome was readmission of the neonate to hospital for any reason within 30 days. Secondary outcomes included arrival to hospital by ambulance, hospitalization for dehydration, for injury, any hospitalization involving resuscitation or assisted ventilation, and all-cause mortality. Results. We studied 7804 infants whose mothers filled a prescription for codeine shortly after delivery and 7804 whose mothers did not. In the primary analysis, infants whose mothers received codeine were no more likely to be readmitted to hospital in the subsequent 30 days than children whose mothers did not (hazard ratio 0.95, 95% confidence interval (CI) 0.81–1.11). Moreover, we found no association between maternal codeine use and the other adverse neonatal outcomes studied. A stratified analysis revealed no differential risk among infants born by Caesarian section (hazard ratio 0.86; 95% CI 0.69–1.08). Conclusions. In this large population-based study, maternal prescription of codeine following delivery was not associated with death or hospitalization in the early neonatal period.

Analgesic Prescribing Practices Can Be Improved by Low-Cost Point-of-Care Decision Support

Context Codeine has become a controversial choice for analgesia in children compared with other commonly available drugs. Objectives To evaluate whether an educational campaign shifted resident prescribing patterns away from codeine toward more appropriate analgesics. Methods Our intervention consisted of a pocket-sized reference card given to all trainees and key staff in an inpatient pediatric acute care unit; pediatrics residents also had the option to attend a one-hour lecture. The pocket card recommended against codeine (including rationale) and gave prescription guidance for our institution's preferred formulary alternative analgesics, which include tramadol and hydrocodone. We used inpatient prescribing data to track the prescribing of codeine and alternative medications over time. Results Following the interventions, there was a significant decrease in the percentage of patients receiving codeine (13.5% of patients received the drug in the year before, 5.4% in the year after, P < 0.0001). Use of hydrocodone-containing analgesics increased overall during the same period (7.4%–16%, P < 0.0001) as did tramadol use (0.2%–2.6%, P < 0.0001). There were no changes in pain management satisfaction scores. Conclusion A simple low-cost educational campaign consisting primarily of a pocket guide to analgesics markedly improved analgesic prescribing patterns, and that improvement extended to services not targeted by the didactic component of our educational campaign. Point-of-care decision support by means of a pocket card may be sufficient for effecting change in medication prescribing patterns of trainees.

Anomalous Observations of Codeine in Patients on Morphine

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of codeine in a patient who is only prescribed morphine has clinical implications. Morphine preparations are known to have small amounts of codeine as an impurity estimated to be about 0.04%. In a population of 535 pain patients prescribed morphine, Kadian, MS Contin, and/or Avinza, the investigators observed 24 samples that contained codeine >20 ng/mL. Fifteen of the 24 contained codeine >20 and <50 ng/mL. Of the 9 samples that were >50 ng/mL, 7 had high levels of codeine (indicating codeine use), 1 was from a patient who had a prescription for codeine, and 1 was also positive for 6-acetylmorphine, indicating heroin use. A control group of 680 patients taking oxycodone was negative for codeine. The finding of codeine was ascribed to the manufacturing process of the morphine medications. Clinicians and laboratories testing urine for drugs should be aware of this possibility.

Repeated dispensing of codeine is associated with high consumption of benzodiazepines

Aims: Our objective was to explore the use of codeine analgesics in individual patients in Norway, giving special attention to the 10% who consume the highest amounts. Methods: We retrieved data from the Norwegian Prescription Database on patients who were dispensed at least one codeine analgesic prescription during 2006. We looked at age and gender specific 1-year periodic prevalence. The 10% of codeine users who were prescribed the highest amounts of the drug that year were further characterized. Age and gender distribution and concurrent high consumption of other potential drugs of abuse were also considered. Results: In the year 2006, a total of 386,836 individuals filled at least one prescription for codeine analgesics from Norwegian pharmacies, excluding cancer patients. The crude prevalence for the use of codeine analgesics was 7.3% and 9.3% of the male and female Norwegian population, respectively. Twelve percent of women and 9% of men who filled a codeine prescription received 120 defined daily doses (DDD) or more of codeine analgesics in 2006 (moderate to high consumers). Fifty percent of those patients (21,759) were also dispensed large amounts of benzodiazepines or carisoprodol over the same period. In comparison, only ten percent of patients who received fewer than 120 DDD of codeine analgesics were dispensed large amounts of benzodiazepines or carisoprodol. Conclusions: A high percentage of the Norwegian population used codeine analgesics. One-year prevalence use of codeine increased with age and was higher for women at all ages. Our study showed that codeine use was mainly sporadic, but that a relatively large sub-group of users were dispensed repeated prescriptions of the drug in combination with other potential drugs of abuse. Key Words: Codeine analgesics, Norwegian Prescription Database, prevalence, dispensed quantity, concurrent use, high consumers, abuse.

Prescription pattern of codeine for non‐malignant pain: a pharmacoepidemiological study from the Norwegian Prescription Database

Opioid prescription for pain relief is increasing. Codeine is the dominating opioid in several European countries, with Norway being among the highest codeine users. To determine whether codeine is primarily used for acute pain or whether there is a prescription pattern indicating problematic opioid use. All pharmacies in Norway are obliged to submit data electronically to the Norwegian Prescription Database at the Norwegian Institute of Public Health on all dispensed prescriptions. Because all prescriptions are identified with a unique person identifier, it is possible to identify all prescriptions to one subject. All subjects who had prescription(s) of codeine dispensed to them in 2004, 2005 or 2006 are included in the study. 385 190 Norwegian persons had at least one prescription of codeine dispensed to them due to non-cancer pain in 2005, corresponding to a 1-year periodic prevalence of 8.3%. 223 778 (58%) received only one prescription in 2005, 121 025 (31%) received more than one prescription but <120 defined daily doses (DDDs), 30 939 (8%) received between 120 and 365 DDDs, 7661 (2%) between 365 and 730 DDDs, while only 1787 (0.5%) exceeded the maximum recommended dose of 730 DDDs. In the latter group, co-medication with benzodiazepines (65%) and carisoprodol (45%) was prevalent. About one in 10 adult persons in Norway were dispensed codeine in 2005. A majority (58%) received codeine only once, most likely for acute pain, whereas a small minority (0.5%) had a prescription pattern indicating problematic opioid use.

The Risk of Motor Vehicle Accidents Involving Drivers With Prescriptions for Codeine or Tramadol

Previous studies have only partially characterized the road-accident risks linked to driving while taking opioid analgesics used for moderate pain.1,2,3,4 A prospective cohort design with data from national population–based registries—the Norwegian Prescription Database and the Norwegian Road Accident Registry—and observation of >8 million person-years were used in order to examine whether a driver who has filled a prescription for codeine or tramadol is at increased risk of being involved in a road accident resulting in injury to persons. Clinical Pharmacology & Therapeutics (2009); 85, 6, 596–599 doi:10.1038/clpt.2009.14

Parental assessment and management of children's postoperative pain: a randomized clinical trial

As day case surgery increases, one needs to improve the management of pain in children at home. This study wished to determine whether the use of a self-report pain scale would result in children receiving more analgesia. Eighty-eight children aged four to 12 years undergoing tonsillectomy, whose parents agreed they could participate, were randomly assigned into two groups. Group A received the routine postoperative advice and a three-day prescription of paracetamol, ibuprofen and codeine. In addition, group B used the Wong-Baker Faces Pain Scale. Seventy-two children completed the study. There was no difference in the total number of analgesics administered to children in the two groups (p = 0.26, Mann- Whitney U-test). It appears that a self-report pain scale does not improve the postoperative management of pain in children at home.

Opiate Addiction Made Easier Bv Plethora of Web Sites

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessOpiate Addiction Made Easier Bv Plethora of Web SitesJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:21 Jul 2006https://doi.org/10.1176/pn.41.14.0018aNew Year's Day 2003 stands out sharply in the memory of Robert Forman, Ph.D., a clinical scientist affiliated with the University of Pennsylvania's Center for Studies of Addiction and Treatment Research Institute.Forman learned that an acquaintance was addicted to opioid medications and obtaining them via the Internet. Forman started perusing the Internet for Web sites offering to sell such medications without a prescription. “I was amazed by what I found,” he told Psychiatric News.He was so dumbfounded by the plethora of such sites that he had located that he and some colleagues decided to launch an explorative study to get a better idea of their prevalence and content.Between March 3, 2003, and September 7, 2004, they conducted 47 Internet searches for such sites. The searches were intended to replicate what Internet users would undertake if they conducted the searches themselves using terms such as, “codeine,” “Vicodin,”“ OxyContin,” “no prescription codeine,” “no prescription Vicodin,” and “no prescription OxyContin.” Each search was limited to the first 100 sites listed because any Internet search usually presents the results that are most relevant to the search term first.The searches yielded 302 Web sites offering to sell opioid medications without a prescription, the team reported in the July American Journal of Psychiatry. The harvest of such Web sites was especially rich when they prefaced their searches with the words “no prescription.” Although both Google and Yahoo provided access to such Web sites, Yahoo generated significantly more sites than Google did.“The whole phenomenon was absolutely jaw-dropping at first—and still is,” Forman said.George Woody, M.D., a professor of psychiatry at the University of Pennsylvania and one of the study investigators, told Psychiatric News that he was both surprised and troubled “by the breadth and depth of offers to sell prescription opioid medications on the Web without any meaningful medical evaluation showing that the person requesting the medication had a problem that required it.”How much Internet users, especially young people, are tapping these Web sites for opioid medications is not known, the study investigators stated in their study report. However, three national drug-use monitoring studies have cited marked increases in prescription opioid use, especially by youth, during the past five years. These increases could well be due to young people's easy access to opioid medications via the Internet, suspected the researchers.And that leads to the question: Why are such Web sites allowed to exist? One reason, the researchers explained in their study report, is because many are located in countries that do not require prescriptions for opioid medications or do not enforce prescription regulations that are in effect in the United States. For example, of the 302 Web sites that were found to be selling opioid medications without a prescription, 189 (65 percent) were registered in 44 countries outside the United States. That leaves, of course, the remaining 113 (35 percent) that were registered in the United States. The U.S. Drug Enforcement Administration is taking action against some of these sites, Forman said, but unfortunately many still abound.Indeed, during their searches for Web sites selling opioid medications without a prescription, the researchers came across Web sites selling numerous other controlled substances as well. These included sedatives, stimulants, steroids, marijuana, opium poppies, coca leaves, nitrous oxide, psilocybin, and peyote. Only cocaine, ecstasy, heroin, and LSD seemed to be missing.All things considered, Wood advised, psychiatrists “should be aware of the possibility that their patients may be purchasing opioid medications [or other controlled substances] on the Web and should ask them about it, especially if their patients are suspected or shown to have a substance use disorder.”The study was funded by the National Institute on Drug Abuse Clinical Trials Network.“The Availability of Web Sites Offering to Sell Opioid Medications Without Prescriptions” is posted at<http://ajp.psychiatryonline.org/cgi/content/full/163/7/1233>.▪ ISSUES NewArchived

The Availability of Web Sites Offering to Sell Opioid Medications Without Prescriptions

This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.

The Availability of Web Sites Offering to Sell Opioid Medications Without Prescriptions

This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.

The black market in prescription drugs

A black market is an illicit trading system that avoids government regulation. It operates outside the law and is driven by the opportunity for profit and the needs of consumers. It is subject to the economic rules of supply and demand and can be rapidly subverted by a change in the laws that make possible its existence. Because the legitimate business of selling prescription drugs is very profitable and highly regulated, opportunities for blackmarket entrepreneurship of these drugs exist in both developed and developing countries. Regulations that govern legitimate access to pharmaceuticals are set by state, national, and international bodies. India has circumvented international patent law by creating a national black market, thereby making it legal to copy a medicine that has been patented elsewhere as long as a different and unique manufacturing process is used. This has allowed the Indian people and other foreign buyers to access highquality medications at a fraction of the cost of the same medication in the USA or Europe, but the practice has understandably been criticised vigorously by multinational pharmaceutical firms and the World Trade Organization.