Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain

Aim:

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

Materials and Methods:

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Results:

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient''s and physician''s global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

Conclusions:

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.     

High‐dose buprenorphine for treatment of high potency opioid use disorder

A 29‐year‐old woman presented to detox for treatment of an opioid use disorder with illicit fentanyl. While in detox, she was started on opioid agonist treatment with buprenorphine/naloxone. Unfortunately, she continued to have withdrawal symptoms despite being optimised to a dose of 32 mg. She was given additional PRNs of buprenorphine/naloxone to a total daily dose of 40 mg, which helped to alleviate her symptoms of withdrawal and cravings. She was stabilised on buprenorphine/naloxone 40 mg daily without any side effects and was discharged to a rehabilitation centre.     

瑞芬太尼与芬太尼在小儿先天性心脏病介入手术麻醉中的效果分析

目的 探讨瑞芬太尼与芬太尼在小儿先天性心脏病介入手术麻醉中的效果。方法 80例小儿先天性心脏病患儿入院后被分为两组,对照组（40例）给予芬太尼麻醉,观察组（40例）给予瑞芬太尼麻醉,依据麻醉前后不同时间的收缩压（SDP）、舒张压（DBP）、心率（HR）,两种麻醉药物的拔管时间、苏醒时间及麻醉用药量及麻醉期间患儿出现的不良反应情况,评价瑞芬太尼与芬太尼在小儿先天性心脏病介入手术麻醉中的效果。结果 与诱导前的基础值相比,麻醉药物诱导后两组SDP、DBP值均降低,组内比较差异有统计学意义（P<0.05）;两组HR水平与诱导前的基础值相比,差异无统计学意义。观察组拔管时间、苏醒时间均短于对照组,组间差异有统计学意义（P<0.05）;但观察组麻醉药物用量多于对照组,两组比较差异显著（P<0.05）。麻醉期间,两组不良反应率相比,差异无统计学意义。结论 瑞芬太尼对小儿先天性心脏介入手术麻醉效果好,对心功能的影响较小,术后能早期拔管,副作用较小,是目前临床上一种理想的麻醉药物。     

Drug metabolism in early infancy: opioids as an illustration

Introduction: Drug dosing in infants frequently depends on body weight as a crude indicator for maturation. Fentanyl (metabolized by Cytochrome P450 3A4) and morphine (glucuronidated by UDP-glucuronosyltransferase-2B7) served as model drugs to provide insight in maturation patterns of these enzymes and provide understanding of the impact of non-maturational factors to optimize dosing in infants.

Areas covered: Systematic searches on metabolism and population pharmacokinetic (Pop-PK) models for fentanyl and morphine were performed. Pre- and post-model selection criteria were applied to assess and evaluate the validity of these models. It was observed that maturational changes have been rather well investigated, be it with variability in the maturational function estimates. The same holds true for Pop-PK models, where non-maturational covariates have also been reported (pharmacogenetics, disease state or external influences), although less incorporated in the PK models and with limited knowledge on mechanisms involved.

Expert opinion: PK models for fentanyl and morphine are currently available. Consequently, we suggest that researchers should not continue to develop new models, but should investigate whether collected data fit in already existing models and provide additional value concerning the impact of (non)-maturational factors like drug-drug interactions or pharmacogenetics.     

芬太尼透皮贴剂治疗带状疱疹及疱疹后神经痛的疗效观察

目的 :观察芬太尼透皮贴剂 (多瑞吉 )对带状疱疹及疱疹后神经痛的疗效 ,本文选择了 31例不宜行神经阻滞的病人作为研究对象。方法 :31例病人在抗病毒治疗的同时均使用 2 5 μg/h的多瑞吉作为首次量 ,如疼痛控制不满意 ,临时追加曲马多缓释片 ,下次换贴时再增加至 5 0 μg/h ,观察其对患者疼痛的缓解程度、生活质量的改善以及出现的并发症。结果 :31例病人经多瑞吉治疗后 ,2例因副反应而终止治疗 ,其余患者疼痛明显缓解 ,VAS评分从 8.5 1± 1.12降至 2 .4 7± 1.2 3,生活质量明显提高 ,部分并发症随时间延长而减少。结论 :多瑞吉能有效地控制带状疱疹及疱疹后神经痛 ,改善病人的生活质量 ,随着病人对多瑞吉的适应 ,部分并发症逐渐减少。     

自控硬膜外分娩镇痛对产程和母婴预后的影响

目的 研究罗哌卡因联合芬太尼于潜伏期即行硬膜外分娩镇痛的有效性及对母婴预后的影响.方法 回顾性分析2008年1月-2010年12月期间在该院妇产科分娩的1 800例初产妇,其中600例自愿接受罗哌卡因联合芬太尼自控硬膜外镇痛的600例产妇为镇痛组,条件类似却未行镇痛的1 200例为对照组,记录两组产妇的镇痛效果、各产程时间、催产素使用情况、分娩方式、产后出血量、新生儿Apgar评分以及不良反应;测定分娩过程中规律宫缩时（T1）、宫口开全时（T2）、胎儿娩出时（T3）、胎盘娩出后30 min（T4）时的空腹血糖（FPG）、空腹胰岛素（FINS）并计算出胰岛素抵抗指数HOMA-IR.结果 所有产程阶段镇痛组的VAS评分均显著低于对照组;镇痛组潜伏期及活跃期时间均较对照组缩短,第二产程时间较对照组长,差异具有统计学意义（P＜0.05）;两组在第三产程时间以及总产程时间上无明显差异（P＞0.05）;镇痛组阴道分娩率、催产素使用率高于对照组;两组新生儿Apgar评分及胎儿窘迫率无显著差别;镇痛组可以减轻胰岛素抵抗程度和血糖升高程度.结论 罗哌卡因联合芬太尼于潜伏期用于PCEA可降低剖宫产率,提高顺产率,减轻胰岛素抵抗程度和血糖升高程度,且不增加母婴并发症,是一种安全、有效、值得大范围推广的分娩镇痛方法     

鞘内注射阿片复合纳洛酮对切口痛大鼠痛行为学及血浆胃动素的影响

目的观察鞘内注射吗啡、芬太尼复合小剂量纳洛酮对切口痛大鼠痛行为学及血浆胃动素(MTL)的影响。方法取鞘内置管成功的健康雄性SD大鼠72只,随机分为6组(n=12):生理盐水(NS)组,切口痛(P)组,吗啡(5μg/kg)+芬太尼(0.25μg/kg)组(MFP组),吗啡+芬太尼+纳洛酮1(0.2 ng/kg)、2(1 ng/kg)、3(5 ng/kg)组(MFPN1、2、3组)。后5组行足跖肌切口。各组取其中6只于鞘内置管前24 h(T0)、造模前24 h(T1)、术后1 h(T2)、3 h(T3)、6 h(T4)、24 h(T5)、48 h(T6)、72 h(T7)检测机械缩足阈值(PWMT)与热缩足反射潜伏期(PWTL),剩余6只于术后6h即刻断头处死,取血浆以ELISA法检测MTL浓度。结果 MFPN2组与NS组各时点PWMT差异无统计学意义,而与NS组相比,T2、T5时点PWTL上调(P<0.05),其余各时点差异无统计学意义。P组、MFPN3组与NS组比较,T2、T3、T4时点PWMT、PWTL显著下调(P<0.05)。而MFPN3组与P组比较,T6时点PWMT及T3、T4时点PWTL下调更为显著(P<0.05)。P、MFP、MFPN1、MFPN3组与NS组比较,术后6 h MTL表达下调(P<0.05)。而MFPN2与NS组MTL表达差异无统计学意义。结论鞘内注射1 ng/kg纳洛酮抑制了吗啡+芬太尼对切口痛大鼠血浆MTL表达的影响,并能上调大鼠热辐射痛阈值,增强了阿片类药物的镇痛效果。     

Inpatient Prescribing and Monitoring of Fentanyl Transdermal Systems: Adherence to Safety Regulations

Background:

National safety guidelines were developed to minimize the occurrence of serious adverse drug events (ADEs) associated with the use of the fentanyl transdermal system (FTS), however, reports of use in opioid-naïve patients for treatment of acute pain and associated ADEs continue to occur.

Objective:

To evaluate the prescribing patterns of the FTS for adherence to recent US regulatory recommendations and identify the impact of health information technology (HIT) on adherence rates.

Methods:

A retrospective pre- and postintervention analysis was performed in hospitalized adult patients receiving FTS. Electronic medication order instructions and text questions were incorporated into FTS electronic medication orders. The primary outcome measure was adherence of FTS medication orders to regulatory guidelines defined as (a) a new order in an opioid-tolerant patient for use in moderate to severe chronic pain or (b) continuation of the documented home dose in use for at least 7 days. Safety measures included respiratory rate and documented ADEs.

Results:

Adherence rates were significantly increased in the postintervention cohort as compared to the preintervention cohort (48.7% vs 85.0%; P < .0001). Incidence of ADEs was significantly lower post intervention (34.7% vs 23.3%; P = .043), including a lower incidence of respiratory depression (16.7% vs 8.3%; P = .043). Documentation was increased in the postintervention cohort (76% vs 100%). However, supporting documentation confirmed responses in only 59.2% of records reviewed.

Conclusions:

Incorporation of HIT via electronic order text questions increased overall adherence rates to regulatory recommendations, increased documentation, and decreased the rate of associated ADEs.