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BACKGROUND: The influences of Oxycodone (OXY) combined with Paclitaxel (PTX) on breast cancer cells are unclear. The present study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis, and migration of human breast cancer SKBR3 cells and the underlying mechanism. METHODS: The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. RESULTS: OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration, and invasion of SKBR3 cells as compared to the control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-Ⅱ, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with the control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. CONCLUSIONS: The present study indicates that OXY can enhance the antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.

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Introduction: Opioids are widely used for pain management, and increased intracranial pressure (ICP) has been evidenced in some cases. We reported a patient with severe cerebral edema after initiating methadone and its complete resolution upon discontinuing the medication. Additionally, a review of the literature is made. Case report: A 53-year-old woman patient with a history of systemic lupus erythematosus developed mechanic chronic lower back pain, refractory to conventional treatments. She presented improvement with oxycodone. She withdrew this medication due to a lack of supplies in her country (Colombia) and showed withdrawal symptoms. She consulted the emergency department, where oral methadone was started and symptom control was achieved. Three days after admission, she presented intense headaches and emesis. A brain CT scan was performed in which severe cerebral edema was appreciated. Methadone was discontinued, and neurological symptoms quickly disappeared. A follow-up brain CT scan was performed later, finding full resolution of the edema. Conclusion: A case of severe cerebral edema associated with the initiation of oral methadone and its rapid resolution without neurological sequelae after its withdrawal is presented, clinicians must be attentive to this adverse event.

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Abstract Background: The influences of Oxycodone (OXY) combined with Paclitaxel (PTX) on breast cancer cells are unclear. The present study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis, and migration of human breast cancer SKBR3 cells and the underlying mechanism. Methods: The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. Results: OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration, and invasion of SKBR3 cells as compared to the control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-II, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with the control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. Conclusions: The present study indicates that OXY can enhance the antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.

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Abstract We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine

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Background: Previous research demonstrated that utilization management (UM) such as prior authorization (PA) or non-formulary (NF) restrictions may reduce pharmacy costs when designed and applied appropriately to certain drug classes. However, such access barriers may also have unintended consequences. Few studies systemically analyzed the impact of major UM strategies to extended-release (ER) opioids on different types of health plans. Objective: This study evaluated, from payer perspective, the impact of formulary restrictions (PA, NF, or step therapy [ST]) for branded oxycodone HCl extended release (OER) on market share, and healthcare resource utilization/costs in ER opioids patients for multiple types of health plans in the United States. Methods: This retrospective, longitudinal case-control study analyzed prescription and outpatient medical claims data (2012 to 2015) for adult ER opioid patients from US plans (commercial,/Medicare, national/regional) that instituted OER PA, NF, or ST. Patients from each restricted plan (cases) were matched to patients in an unrestricted plan (controls) on key patient characteristics. ER opioid market share and healthcare resource utilization/costs for both cases and controls were evaluated for the 6-month period before and after the formulary restriction dates. A difference-in-differences (DiD) approach was utilized to evaluate change in the total per patient per month (PPPM) healthcare utilization and costs. Results: The study comprised 1622 (national commercial PA), 2020 (regional commercial PA), 34 703 (national commercial ST), and 4372 (national Medicare NF) cases and equivalent number of controls. OER market share decreased after the formulary restrictions, with the national Medicare NF plan showing the greatest decrease (9.2%). DiD analyses indicated that PPPM office visit change in the PA and NF plans were non-significant (decreased by 0.1 and 0.2, P>0.05), but significant in the ST plan (increased by 0.1, P=0.0001). For most plans, no significant total monthly cost change was observed; PPPM costs decreased by $48.74 and $59.87 in ST and regional PA plans and increased by $37.90 in national NF plans (all P>0.05). Conclusions: This study observed that despite reducing the market share of OER, OER formulary restrictions had negligible impact on overall ER opioid utilization, and did not result in substantial pharmacy/medical cost savings.

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OBJETIVO: Muitos pacientes apresentam intensa dor após artroplastia, que pode resultar em perda de qualidade de vida e ônus financeiro considerável devido ao custo de medicamentos analgésicos, intervenções e hospitalizações. O cloridrato de oxicodona de liberação prolongada é um opioide de ação semelhante à morfina com eficácia comprovada no tratamento da dor de moderada a forte intensidade. O objetivo deste estudo foi avaliar custos de medicamentos e hospitalizações em pacientessubmetidos ao tratamento com oxicodona de liberação prolongada comparado à morfina, em regime "se necessário" no manejo da dor pós artroplastia, sob as perspectivas dos sistemas de saúde público e privado, no Brasil. MÉTODOS: Um modelo de decisão foi desenvolvido para análisede dois cenários. Em ambos, os pacientes do grupo 1 receberam oxicodona de liberação prolongada e opioide de liberação imediata. Em relação ao grupo 2, no cenário 1, os pacientes receberam opioide de liberação imediata e, no cenário 2, opioide de liberação imediata e placebo. Custos foramobtidos a partir de listas de preços oficiais. No cenário 1, o horizonte temporal foi relativo ao período de tratamento de 3 semanas e, no cenário 2, determinado através do período de hospitalização. Taxas de desconto não foram aplicadas. Uma análise de sensibilidade univariada foi realizada para avaliar diferentes categorias hospitalares. RESULTADOS: No cenário 1, sob a perspectiva do sistema de saúde público, os custos totais foram R$ 1.486 e R$ 1.520 por paciente tratado nos grupos 1 e 2, respectivamente. Na perspectiva do sistema de saúde privado, os custos totais foram R$ 3.132 e R$ 3.457 por paciente tratado nos grupos 1 e 2, respectivamente. No cenário 2, sob perspectiva do sistema de saúde público, os custos totais foram R$ 3.299 e R$ 3.591 por paciente tratado nos grupos 1 e 2, respectivamente. Na perspectiva do sistema de saúde privado, os custos totais foram R$ 7.197 e R$ 8.181 por paciente tratado nos grupos 1 e 2, respectivamente. Na análise de sensibilidade univariada, todos os cenários avaliados continuaram consistentes e favoráveis à utilização da oxicodonade liberação prolongada. CONCLUSÃO: Por diminuir o tempo de hospitalização, a utilização da oxicodona de liberação prolongada pode ocasionar redução de custos totais do tratamento da dor em pacientes submetidos a artroplastia

OBJECTIVE: Many patients have severe pain after arthroplasty, which can result in loss of quality of life and considerable financial burden due to the cost of analgesic drugs, interventions and hospitalizations. The extended-release oxycodone hydrochloride is an opioid with similar action to morphine with proven efficacy in the treatment of moderate to severe pain. The objective of this study was to evaluate drug and hospitalizations costs for patients undergoing treatment with extended-release oxycodone comparedto morphine in a "if necessary" regime in the management of pain post-arthroplasty, from public and private health care systems perspectives in Brazil. METHODS: A decision model was developed to analyze two scenarios. In both, patients in group 1 received extended-release oxycodone and immediate-release opioid. Regarding group 2, in scenario 1, patients received immediate-release opioid and, in scenario 2, immediate-release opioid and placebo. Costs were obtained from official prices lists. In scenario1, time horizon was related to a 3-week treatment period and, in scenario 2, determined by the hospitalization period. Discount rates were not applied. Univariate sensitivity analysis was performed to evaluate different hospital categories. RESULTS: In scenario 1, from the public perspective, total costs were 1,486 BRL and 1,520 BRL per patient treated in groups 1 and 2, respectively. From the private perspective, total costs were 3,132 BRL and 3,457 BRL per patient treated in groups 1 and 2, respectively. In scenario 2, from the public perspective, total costs were 3,299 BRL and 3,591 BRL per patient treated in groups 1 and 2, respectively. From the private perspective,total costs were 7,197 BRL and 8,181 BRL per patient treated in groups 1 and 2, respectively. In the univariate sensitivity analysis, all evaluated scenarios remained consistent and favorable to the use of extended-release oxycodone. CONCLUSION: By decreasing the length of hospital stay, extended-release oxycodone can result in reduction of total post-arthroplasty pain related costs

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Objective: To evaluate the safety and tolerability of controlled-release oxycodone in the treatment of postoperative pain of head and neck oncologic resections. Methods: We conducted a prospective, observational and open study, with 83 patients with moderate to severe pain after head and neck oncological operations. All patients received general anesthesia with propofol, fentanyl and sevoflurane. Postoperatively, should they have moderate or severe pain, we began controlled-release oxycodone 20 mg 12/12 b.i.d on the first day and 10 mg b.i.d. on the second. We assessed the frequency and intensity of adverse effects, the intensity of postoperative pain by a verbal numeric scale and the use of rescue analgesia from 12 hours after administration of the drug and between 7 and 13 days after the last oxycodone dose. Results: The most common adverse events were nausea, vomiting, dizziness, pruritus, insomnia, constipation and urinary retention, most mild. No serious adverse events occurred. In less than 12 hours after the use of oxycodone, there was a significant decrease in the intensity of postoperative pain, which remained until the end of the study. The rescue medication was requested at a higher frequency when the opioid dose was reduced, or after its suspension. Conclusion: Controlled release oxycodone showed to be safe and well tolerated and caused a significant decrease in post-operative pain. .

Objetivo: avaliar a segurança e a tolerabilidade da oxicodona de liberação controlada no tratamento da dor pós-operatória de ressecções oncológicas de cabeça e pescoço. Métodos: estudo prospectivo, observacional e aberto. Foram estudados 83 pacientes com dor de moderada a intensa após operações oncológicas de cabeça e pescoço. Todos receberam anestesia geral com propofol, fentanil e sevoflurano. No pós-operatório, quando apresentaram dor moderada ou intensa, foi iniciada oxicodona de liberação controlada, 20mg de 12/12 horas no primeiro dia e 10mg de 12/12 horas no segundo dia. A frequência e a intensidade de efeitos adversos, a intensidade da dor pós-operatória pela escala verbal numérica e o uso de medicação analgésica de resgate foram avaliadas de 12/12 horas após a administração do medicamento e entre 7 e 13 dias após a última dose de oxicodona. Resultados: os efeitos adversos mais frequentes foram: náusea, vômito, tontura, prurido,insônia, constipação e retenção urinária, sendo a maioria, de leve intensidade. Não ocorreram eventos adversos graves. Em menos de 12 horas após o emprego da oxicodona, ocorreu diminuição significativa da intensidade da dor pós-operatória, que permaneceu até o final do estudo. A medicação de resgate foi solicitada em uma frequência maior quando a dose do opioide foi reduzida,ou após sua suspensão. Conclusão: aoxicodona de liberação controlada demonstrou ser segura e bem tolerada e promoveu diminuição significativa da dor pós-operatória. .

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Introducción: Estudio descriptivo que busca evaluar la experiencia de nuestra Unidad con uso de oxicodona, opioide, con perfil de analgesia similar a morfina, en pacientes con dolor por cáncer avanzado. Objetivo: Analizar la eficacia analgésica de oxicodona (de liberación controlada), perfil de paciente, dosis utilizadas y efectos adversos descritos. Metodología: Estudio descriptivo-retrospectivo. Revisión de fichas de pacientes tratados con oxicodona durante años 2009 y 2010 en UADyCP. Respuesta analgésica estimada con test de Wilcoxon. Estadística descriptiva en resto de las variables. Evaluación de dolor según Escala Numérica de rango 0 a 10. Resultados: Muestra 64 pacientes: 34 mujeres y 30 hombres. Edad promedio 59,5 años. Tipo dolor: somático (53 por ciento), visceral (19 por ciento), neuropático (5 por ciento), mixto (23 por ciento). Tiempo medio de uso oxicodona: 3,2 meses. EVA 8 (5-9) antes del inicio de oxicodona. EVA 3 (2-8) con oxicodona (p<0,0005). La dosis promedio utilizada fue de 40mg/día (20-80mg/día). 44 pacientes con efectos adversos: náuseas (22 por ciento), constipación (18 por ciento ), prurito (15 por ciento) anorexia (13 por ciento). 31 por ciento se encontraba en tratamiento previo con opioides débiles, 62 por ciento con metadona o morfina. 7 por ciento recibió oxicodona como terapia inicial. Las principales razones para el cambio de oxicodona fueron mal control analgésico (54 por ciento), necesidad de uso de medicamentos vía subcutánea (29 por ciento), intolerancia al medicamento (17 por ciento). Conclusiones: Oxicodona permite adecuado control analgésico. Dosis utilizadas son inferiores a las descritas en la literatura y su perfil de efectos adversos es similar a otros opioides. Constituye alternativa en intolerancia a morfina o rotación de opioides.

Introduction: Descriptive study that seeks to evaluate the experience of our unit with the use of oxycodone, an opioid with a profile similar to morphine, in patients with advanced cancer pain. Objective: to evaluate analgesic efficacy of oxycodone (controlled release), patient profile, doses and adverse effects. Methodology: A descriptive, retrospective study. Review records of patients treated with oxycodone during 2009 and 2010. Analgesic response estimated with Wilcoxon test. Descriptive statistics on other variables. Assessment of pain by numeric scale range 0 to 10.Results: 64 patients. 34 women and 30 men were analyzed Mean age 59.5 years. Type of Pain: Somatic (53 per cent), visceral (19 per cent) neuropathic (5 per cent) mixed (23 per cent). Average time of oxycodone use: 3.2 months . Average VAS before starting Oxycodone 8 (5-9). Average VAS with oxycodone 3 (2-8) (p <0.0005). The average dose used was 40mg/day (20-80mg/day). Adverse effects: in 44 patients: nausea (22 per cent), constipation (18 per cent), pruritus (15 percent), anorexia (13 per cent). 31 per cent patients were using weak opioids previously, 62 per cent was using methadone or morphine. 7 per cent received oxycodone as initial therapy. The main reasons for discontinue the use of oxycodone were poorly controlled pain (54 percent), need for subcutaneous drug use (29 per cent) drug intolerance (17 per cent). Conclusions: Oxycodone allows adequate pain control. Doses used were lower that the described in the literature and its adverse effect profile is similar to other opioids. Alternative in intolerance to morphine or opioid rotation.

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Este artigo contém as conclusões de reunião de 17-18 de novembro de 2006 do Grupo Brasileiro de Estudo em Síndrome das Pernas Inquietas (GBE-SPI) sobre diagnóstico e tratamento de SPI. Reiterou-se que se trata de condição de diagnóstico exclusivamente clínico, caracterizada por sensação anormal localizada, sobretudo, mas não exclusivamente, em membros inferiores, com piora noturna e alívio por movimentação da parte envolvida. Agentes terapêuticos com eficácia comprovada por estudos classe I são agonistas dopaminérgicos, levodopa e gabapentina enquanto que ácido valpróico de liberação lenta, clonazepam, oxicodona e reposição de ferro têm eficácia sugerida por estudos classe II. As recomendações do GBE-SPI para manejo de SPI primária são medidas de higiene do sono, suspensão de agentes agravantes de SPI, tratamento de comorbidades e agentes farmacológicos. Para estes as drogas de primeira escolha são agentes dopaminérgicos; segunda escolha são gabapentina ou oxicodona; e terceira escolha são clonazepam ou ácido valpróico de liberação lenta.

This article contains the conclusions of the November 17-18, 2006 meeting of the Brazilian Study Group of Restless Legs Syndrome (GBE-SPI) about diagnosis and management of restless legs syndrome (RLS). RLS is characterized by abnormal sensations mostly but not exclusively in the legs which worsen in the evening and are improved by motion of the affected body part. Its diagnosis is solely based on clinical findings. Therapeutic agents with efficacy supported by Class I studies are dopamine agonists, levodopa and gabapentine. Class II studies support the use of slow release valproic acid, clonazepan and oxycodone. The GBE-SPI recommendations for management of SPI are sleep hygiene, withdrawal of medications capable of worsening the condition, treatment of comorbidities and pharmacological agents. The first choice agents are dopaminergic drugs, second choice are gabapentine or oxycodone, and the third choice are clonazepan or slow release valproic acid.

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