Health Canada advisory impacts on the prevalence of oral codeine use in the Pediatric Canadian population: comparative study across provinces.

Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from - 0.6 to - 18.4%) in children and from - 2.1 to - 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

Síndrome de Pisa asociado a codeína / Pisa syndrome associated with codeine

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Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery / Comparação dos efeitos analgésicos pós-operatórios de naproxeno sódico e naproxeno sódico-fosfato de codeína em artroscopia de menisco

ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p < 0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p < 0.001). Meperidine consumption was higher in Group N compared with Group NC (p < 0.001). There was no difference between groups with respect to side effects (p > 0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os anti-inflamatórios não esteroides (AINEs) são frequentemente usados para controlar a dor após artroscopia. A adição de um opiáceo oral eficaz (codeína) aos AINEs pode ser mais efetiva e diminuir o consumo de opiáceo parenteral no pós-operatório. O objetivo deste estudo foi comparar a eficácia e os efeitos colaterais de naproxeno sódico e uma nova preparação, naproxeno sódico-fosfato de codeína, quando administrados preventivamente para meniscectomia artroscópica. MÉTODOS: Foram randomicamente divididos em dois grupos 61 pacientes para receber naproxeno sódico por via oral (Grupo N) ou naproxeno sódico-fosfato de codeína (Grupo NC) antes da cirurgia. A cirurgia foi feita sob anestesia geral. Meperidina intravenosa foi iniciada por meio de analgesia controlada pelo paciente (ACP) para todos os pacientes. O desfecho primário foi o escore de dor na primeira hora de pós-operatório, avaliada com a escala visual snalógica (EVA). A sedação foi avaliada com a escala de sedação de Ramsey. A primeira demanda de ACP, o consumo de meperidina no pós-operatório, os efeitos colaterais e os dados hemodinâmicos também foram registrados. RESULTADOS: Os grupos foram demograficamente comparáveis. As medianas dos escores EVA tanto em repouso quanto em movimento foram significativamente menores no Grupo NC comparado com o Grupo N; exceto para movimento na avaliação de 18 horas (p < 0,05). A mediana do tempo até a primeira demanda de ACP foi menor no Grupo N em comparação com o Grupo NC (p < 0,001). O consumo de meperidina foi maior no Grupo N em comparação com o Grupo NC (p < 0,001). Não houve diferença entre os grupos em relação aos efeitos colaterais (p > 0,05). CONCLUSÕES: A combinação de naproxeno sódico-fosfato de codeína forneceu analgesia mais efetiva que naproxeno sódico, sem aumentar os efeitos colaterais.

Imagen ecográfica del hidroadenoma poroide / Ultrasound Image of Poroid Hidradenoma

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Eficácia analgésica da associação de 30mg do fosfato de codeína com 500mg do paracetamol após exodontias de terceiros molares inferiores impactados / Analgesic efficacy of codeine phosphate 30mg association with paracetamol 500mg after extraction of impacted lower third molars

Avaliar a eficácia analgésica da associação de 30mg do fosfato de codeína com 500mg do paracetamol após exodontias de terceiros molares inferiores impactados. Foi realizado um estudo clínico bilateral com uma amostra de 47 pacientes. Em um dos lados, todos os pacientes receberam a dosagem de 30mg do fosfato de codeína em associação com 500mg do paracetamol após exodontia (grupo teste). Para a exodontia contralateral, foi disponibilizado outro frasco contendo cápsulas idênticas, porém com a dosagem de 500mg de paracetamol (grupo controle). 100% dos pacientes do grupo teste não necessitaram utilizar a medicação resgate e não consumiram doses adicionais da medicação após as cirurgias. No grupo controle, 44,7% dos participantes relataram o uso do medicamento resgate. O consumo total de comprimidos no grupo teste foi, em média, inferior quando comparados ao lado contralateral. 80,8% dos pacientes relataram maior conforto, quanto ao critério da dor, no lado em que foi utilizado a dosagem de 30mg de fosfato de codeína associado a 500mg de paracetamol. Os efeitos colaterais estiveram mais presentes no grupo teste, sendo mais comum o relato de sonolência (34%) e tontura (31,9%), não havendo relato de abandono desta medicação por nenhum dos pacientes. Concluímos que a dosagem de 30mg do fosfato de codeína associada a 500mg de paracetamol apresentou resultados favoráveis no controle da dor e uma baixa incidência de efeitos colaterais...

To assess the analgesic efficacy of regular dosage of codeine phosphate 30mg association with paracetamol 500mg after extraction of impacted lower third molars. We performed a bilateral clinical study analyzing a sample of 47 patients. All patients received a 30mg codeine phosphate dosage in combination with paracetamol 500mg after extraction (test group). For the contralateral tooth extraction, we had another bottle available containing identical capsules, with a 500mg paracetamol dosage (control group). 100% of the test group patients did not need to use rescue medication and did not consume additional doses of medication after surgeries. In the control group, 44.7% reported the use of rescue medication. Total consumption of pills in the test group was on average lower than the contralateral side. 80.8% of patients reported greater comfort, as the criterion of pain in the side that was used 30mg codeine phosphate dosage associated with paracetamol 500mg. The adverse effects were more present in the test group, with sleepiness being more common (34%) and dizziness (31.9%), without any patient medication abandonment. We conclude that the 30mg codeine phosphate dosage associated with paracetamol 500mg showed favorable results in controlling pain associated with a low incidence of side effects...

Pancreatitis secundaria a paracetamol-codeína / Pancreatitis due to acetaminophen-codeine

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Codeine challenge in chronic urticaria patients

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Pharmacological stimuli in asthma/urticaria / Estimulos farmacológicos en el asma/urticaria

Background: The use of opioids as analgesics is becoming increasingly widespread, which may have repercussions in patients with urticaria or asthma, as these agents frequently cause adverse reactions. Material and methods: We present three patients who developed allergic reactions after receiving codeine: two patients who developed acute urticaria, and a third asthmatic patient receiving specific immunotherapy who developed bronchospasm. Skin prick-testing (SPT) and intradermal reaction (IDR) tests with various opioids were performed, followed by controlled oral challenge. Prick tests and IDR were also carried out in 20 controls. Results: Similar SPT and IDR results were recorded in the three patients and in the controls. In the case of controlled oral challenge with codeine, patient 1 suffered bronchospasm, while patient 2 developed generalized urticaria. The test was not performed in the third patient. All of the patients tolerated tramadol 50 mg without problems. We advised the use of tramadol as analgesic and fentanyl or remifentanil as anesthetics. Discussion: In these types of manifestation, the pharmacological properties of the opioids used are highly important, particularly as regards their histamine-releasing potential. Codeine, morphine and pethidine present the greatest histamine-releasing capacity, while tramadol, fentanyl and remifentanil do not release histamine and their use is thus recommended in pulmonary disease requiring opioid administration. Cutaneous symptoms are more frequently caused by opioids than by respiratory symptoms, since these drugs act on the MTC mast cell population, which is more prevalent in the skin than in the lungs. Some of this action is inhibited by naloxone. Conclusions: In most patients, these reactions are not IgE-mediated. Consequently, SPT and IDR are of little diagnostic value, and controlled oral challenging with the suspect drug or with one of the non-histamine releasing agents should be used. The patch test is useful in occupational contact dermatitis

Introducción: Como fármacos analgésicos, cada vez está más extendido el uso de opiáceos y éstos pueden tener repercusiones sobre pacientes con urticaria o asma. La mayoría de las veces la causa es un efecto secundario. Material y Métodos: Presentamos dos pacientes que han tenido una urticaria tras la toma de codeína y otra paciente asmática que está recibiendo inmunoterapia y tiene crisis de broncoespasmo tras la toma de éste fármaco. Se realizan prick-test e IDR con varios opiáceos, y tras esto se realiza exposición oral controlada. También se realizan pricks e IDR a 20 controles. Resultados: En los tres casos y en los controles se obtienen resultados similares de los pricks y de las IDR. En la exposición oral controlada con codeína, la paciente 1 sufre un broncoespasmo, la 2 una urticaria generalizada y la 3 no se realiza. Las tres toleran tramadol 50mg sin problemas. Se recomienda el uso de tramadol como analgésico y fentanilo o remifentanilo como anestésicos. Discusión: En este tipo de cuadros las propiedades farmacológicas de los opiáceos son muy importantes, puesto que van a venir marcados por la potencia de liberación de histamina. La codeína, la morfina y la petidina, son los mayores liberadores y por el contrario, el tramadol, el fentanilo y el remifentanilo no lo son y están recomendados en patología pulmonar que necesiten opiáceos. Los opiáceos suelen producir en mayor número de ocasiones cuadros cutáneos por que actúan sobre todo sobre los MTC que son más numerosos en la piel que en el pulmón. La Naloxona inhibe en parte ésta acción. Conclusiones: La mayoría de reacciones de este tipo no son IgE mediadas, por lo que los pricks e IDR no tienen ningún valor, y se debe de recurrir a la exposición controlada con el fármaco implicado o con uno de los no liberadores de histamina. Las pruebas del parche si que tienen utilidad en las dermatitis de contacto ocupacionales

Pancreatitis due to codeine

Pancreatitis is a rare adverse effect of codeine. We report the case of a 42-year-old man who suffered from epigastric pain 1 hour after taking a tablet containing amoxicillin plus clavulanic acid (500/125 mg) and another tablet containing acetaminophen plus codeine (500/30 mg) for a respiratory infection. He was admitted to the emergency room and was treated with metamizol and pantoprazole. A few minutes after receiving intravenous doses of both drugs he developed a maculopapular and itching eruption with facial angioedema. Laboratory tests showed high levels of serum amylase, GOT, GPT and total bilirubin. Serological tests for several viruses showed no evidence of recent infection. Ultrasonography was negative for biliary lithiasis and showed only cholecystectomy performed in 2000. The patient was sent to our department where skin prick and oral challenge tests were performed with negative results. For ethical reasons, oral challenge with codeine was not carried out. We believe that our patient had codeine-induced pancreatitis. The most likely underlying pathophysiological mechanism was probably codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Allergy departments should be aware of possible non-immunological adverse

La pancreatitis es un efecto secundario raramente producido por la codeína. Presentamos el caso de un paciente de 42 años que sufrió dolor epigástrico, una hora después de la ingesta de un comprimido de amoxicilina-clavulánico (500/125 mg) y otro de paracetamol-codeína (500/30 mg) por un cuadro infeccioso de vías altas. Acude al servicio de urgencias donde es tratado con metamizol y pantoprazol por vía intravenosa, presentando unos minutos después de su infusión, una erupción máculo-papulosa muy pruriginosa acompañada de angioedema facial. Las pruebas de laboratorio mostraron niveles elevados de amilasa sérica, GOT, GPT y bilirrubina total. Las pruebas serológicas de distintos virus no mostraron evidencia de infección reciente. El estudio ecográfico fue negativo para litiasis biliar y solamente mostró la existencia de una colecistectomía realizada en el año 2000. Fue derivado a nuestra sección donde se le hicieron pruebas cutáneas y de provocación con resultado negativo con los fármacos implicados, excepto con codeína por razones éticas. Pensamos que la codeína fue la responsable del cuadro de pancreatitis sufrido por el paciente y el probable mecanismo patofisiológico subyacente habría sido el espasmo del esfínter de Oddi inducido por la codeína, combinado con una disfunción relacionada con la colecistectomía previa. Por tanto, los servicios de Alergia deben considerar la posible existencia de reacciones adversas de etiología no inmunológica, que pueden originar patologías graves a los pacientes

Avaliaçäo clínica entre o paracetamol e paracetamol mais codeína em cirurgia bucal / Clinic evaluation between acetaminophen and acetaminophen plus codeine in oral surgery

O propósito desta pesquisa é avaliar comparativamente em duplo-cego cruzado randomizado, a eficácia dos analgésicos paracetamol (500 mg) e paracetamol (500 mg) mais codeína (30 mg) no controle da pós-operatória. O efeito das drogas foi mensurado pelos pacientes e investigado, através de escalas visuais análogas e escalas de categorias durante 24 horas. O paracetamol mais codeína apresentou ligeira superioridade em relaçäo ao paracetamol, porém estatisticamente näo significantes