Efficacy of Fentanyl Buccal Tablets for Patients Who Cannot Retain at the Above a Rear Molar between the Upper Cheek and Gum

Fentanyl buccal tablets place the tablet at the buccal site (above a rear molar, between the upper cheek and gum) and wait until it dissolves, but some patients may not be able to retain it due to defects of the maxillary molars. The aim of this study was to evaluate the effectiveness and safety of fentanyl buccal tablets when they were used outside the buccal site. Seven patients were treated with fentanyl buccal tablets outside the buccal site. For each of 5 episodes in which effective dose was identified, were investigated to average pain intensity assessed on a 0 to 10 numerical rating scale at 30 min postadministration and reduction in pain intensity of more than 33%. Pain intensity significantly decreased at 30 min postadministration in 5 patients with effective doses identified (p<0.001). In 92.0% of episodes treated, there was a reduction in pain intensity of more than 33%. Adverse events were somnolence and nausea with mild. However, these effects did not result in discontinuation of medication. Our findings suggested that fentanyl buccal tablets can be used effectively and safely even when patients used outside the buccal site.

Awareness of Short-acting Opioid Formulation and Rapid-onset Opioid Formulation in Healthcare Professionals: A Questionnaire Survey

Objective: The present study was conducted to determine the level of awareness about the difference between short-acting opioid (SAO) and rapid-onset opioid (ROO) formulation. Methods: A questionnaire survey was conducted to evaluate levels of awareness regarding the definition of cancer breakthrough pain, how to use the ROO formulation, and the difference between SAO and ROO formulation among physicians, nurses, and pharmacists. The surveillance period is between December 1, 2017 and December 31, 2017. Results: We received responses from 35 physicians, 102 nurses, and 171 pharmacists. The awareness of the difference between SAO formulation and ROO formulation across all occupation groups was approximately 3.8 in 11 steps from 0 to 10. Regarding the appropriate use of the ROO formulation, there was a tendency for variation among respondents in awareness about items referring to “the starting dose” and “the starting dose does not depend on the daily dose of the opioid analgesic administered on time.” Conclusion: The results of the present study suggest that it is necessary for each healthcare professional to reconfirm their knowledge of ROO formulation in the future and ensure appropriate administration.

Overview of the Management of Chronic Non-Cancer Pain in Patients with Spinal Disease / 대한척추외과학회지

STUDY DESIGN: Cross-sectional, multi-center survey study. OBJECTIVES: The objective of this study was to investigate the pain status, pain management methods, and pain experience after treatment among patients suffering from chronic non-cancer pain due to spinal disease. SUMMARY OF LITERATURE REVIEW: No thorough investigation of the current status of chronic non-cancer pain management in patients with spinal disease has recently been reported. MATERIALS AND METHODS: We surveyed 330 patients with chronic non-cancer pain who visited spine clinics in Korea. RESULTS: Prior to treatment, 86.7% of the patients had severe pain and 99.4% of the patients had taken oral analgesics for pain control. After treatment, the percent of patients with severe pain was reduced to 42.1%, and 52.4% of patients responded that they experienced intermittent pain. End of dose failure was experienced by 29.1% of patients, and 41.7% of patients experienced pain again 3–6 hours after taking analgesics. Furthermore, 8.2% of patients experienced breakthrough pain, and 29.1% of patients experienced pain that interfered with sleeping. CONCLUSIONS: Many patients with chronic pain reported experiencing pain due to end of dose failure after medication. As the causes of chronic pain are complex, appropriate analgesics should be considered and selected for effective pain management.

Factors Influencing Pain Medication Preference for Breakthrough Cancer Patients and Their Application to Treatments: Survey on Physicians / 한국호스피스완화의료학회지

PURPOSE: The purpose of this study was to assess the factors influencing the rescue medication decisions for breakthrough cancer patients and evaluate treatments using the factors. METHODS: Based on the results of an online survey conducted by the Korean Society of Hospice and Palliative Care from September 2014 through December 2014, we assessed the level of agreement on nine factors influencing rescue medication preference. The same factors were used to evaluate oral transmucosal fentanyl lozenge, oral oxycodone and intravenous morphine. RESULTS: Agreed by 77 physicians, a rapid onset of action was the most important factor for their decision of rescue medication. Other important factors were easy administration, strong efficacy, predictable efficacy and less adverse effects. Participants agreed that intravenous morphine produced a rapid onset of action and strong and predictable efficacy and cited difficulty of administration and adverse effects as negative factors. Oral oxycodone was desirable in terms of easy administration and less adverse effects. However, its onset of action was slower than intravenous morphine. While many agreed to easy administration of oral transmucosal fentanyl lozenge, the level of agreement was low for strength and predictability of its efficacy, long-term durability and sleep improvement. CONCLUSION: Rapid onset of action is one of the important factors that influence physicians' selection of rescue medication. Physicians' assessment of rescue medication differed by medication.

Initial titration with 200 μg fentanyl buccal tablets: a retrospective safety analysis in Korean cancer patients

BACKGROUND/AIMS: Managing breakthrough pain (BTP) is important for many cancer patients because of the rapid onset and unpredictable nature of the pain episodes. Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for BTP management. However, FBT titration is needed to optimize BTP management. In this study, we aimed to evaluate the safety and efficacy of initiating 200 μg FBTs in Korean cancer patients. METHODS: A retrospective analysis of medical records was performed on all advanced cancer patients treated with FBTs for BTP between October 2014 and July 2015. Patients who received initial doses of 200 μg FBTs for at least 3 days and cases in which FBT was available at doses of 200, 400, and 800 μg were included. RESULTS: A total of 56 patients with a median age of 62 years (range, 32 to 80) were analyzed, 61% of whom were male. The median and mean values of morphine equivalent daily doses were 60 mg/day (range, 15 to 540) and 114.8 ± 124.8 mg/day, respectively. The most frequent effective doses of FBT were 200 μg (41 patients, 74%) and 400 μg (12 patients, 21%). Three patients (5%) could not tolerate 200 μg of FBT and discontinued treatment. Nausea, vomiting, somnolence, and dizziness were the most frequent treatment-related adverse events (AEs), and all AEs were grade 1 (mild) or 2 (moderate). CONCLUSIONS: FBT at the initial 200 μg dosage was well-tolerated and effective as a BTP management strategy in Korean cancer patients. Further prospective studies are needed to determine appropriate initiating doses of FBT in Korean patients with opioid tolerance.

A Survey of the Current Status of Fentanyl Sublingual Tablets and Evaluation of Problems Associated with Their Proper Use / 日本プライマリ・ケア連合学会誌

<p><b>Objectives: </b>A survey was conducted to investigate the usability and safety of fentanyl sublingual tablets (FST) and to examine problems associated with their proper use.</p><p><b>Methods: </b>Subjects were 18 cancer inpatients who received FST for breakthrough pain in their pharmacological cancer pain management. Changes in the pain score and the occurrence of adverse effects (nausea, vomiting and somnolence) were compared before and after FST administration.</p><p><b>Results: </b>The pain score before FST administration was 6.4±2.4, and this was significantly improved to 3.4±2.8 at 30 min after administration (p<0.01). Somnolence occurred significantly more often 30 min and 2 h after FST administration than immediately before administration (p<0.05). There were no differences in the occurrence of nausea and vomiting before or after FST administration. Nine patients receiving FST therapy developed xerostomia, but there were no significant changes in the pain score or occurrence of adverse effects while they had xerostomia.</p><p><b>Conclusion: </b>It is essential to observe the oral condition to judge whether FST therapy is indicated, and FST should be administered after providing sufficient oral care. The results indicate the possibility of increased occurrence of somnolence as an adverse effect.</p>

A Case Report on the Use of the Rapid-onset Opioid Fentanyl Resulting in Numbness and Pain in the Mouth and Taste Disturbance

<p>Introduction: The rapid-onset opioid fentanyl is used to treat breakthrough pain in the management of cancer pain. Case Report: A 33-year-old woman started to receive palliative radiation for multiple spinal metastases and pathological fracture of the sacrum following surgery for right breast cancer. Although oxycodone sustained-release tablets and oxycodone powder had been used for the treatment of pain, there had been no alleviation in response to oxycodone powder at times that she experienced breakthrough pain. Therefore, the patient was switched to rapidly acting fentanyl citrate sublingual tablets. An analgesic effect was obtained, but numbness of the lower lip and taste disturbance emerged. Furthermore, pain in the lower jaw emerged and eating became difficult. Therefore, the patient was switched to fentanyl citrate buccal tablets. However, once the agents were dissolved and spread inside the mouth, the same symptoms emerged. Conclusion: Because the same symptoms were observed even after switching agents, fentanyl citrate or the common ingredient contained in both agents appeared to be the cause of this event.</p>

Breakthrough pain experiences of advanced cancer patients:a qualitative research / 中国实用护理杂志

Objective To get further insight into the breakthrough pain experiences in advanced cancer patients in order to provide targeted nursing measures for breakthrough pain patients. Methods Semi structured interviews were performed in 12 advanced cancer patients. Colaizzi analysis program was used to analyze, induct and extract the themes. Results The breakthrough pain experiences of advanced cancer patients were as follows:overall perception of breakthrough pain;the experience when experiencing breakthrough pain; personal growth related to breakthrough pain. Conclusions Nurses should provide sufficient information to patients timely, consider patients′needs and combine with non-drug methods to better manage breakthrough pain to improve patients′experience about breakthrough pain.

Analgesic effects of 0.15% ropivacaine for the breakthrough pain during labor after epidural analgesia / 临床麻醉学杂志

Objective To compare the analgesic effects for breakthrough pain after epidural la-bor analgesia during vaginal delivery by different concentrations of ropivacaine with or without sufen-tanil.Methods A total of 60 full term nulliparous women with singleton (ASA physical status Ⅰ orⅡ)were included,who received successful epidural labor analgesia and experienced breakthrough pain during the first labor phrase.They were randomized into group A (n = 30)and group B (n =30),rescue dose with 0.1 5% pure ropivacaine and 0.08% ropivacaine plus sufentanil 0.4 μg/ml,re-spectively.The VAS score,modified Bromage score,boluses of rescue dose,consumption of analge-sics and oxytocin,durations of labor phrase,modes of labor,and side effects during labor were ob-served.Results Compared with group B,the VAS score 20 min after rescue dose for the break-through pain,the frequency of rescue,the dosage of sufentanil and the incidence of side effects such as itching and urine retention were significantly decreased in group A.Modified Bromage score was 0 in each group. The cases using oxytocin, labor time and childbirth way were similar. Conclusion Rescue dose of 0.1 5% ropivacaine can provide better analgesic effect than those of 0.08% ropivacaine plus sufentanil 0.4 μg/ml for the breakthrough pain during the first labor phrase, with less side effects and higher satisfaction scales.

Physician's Attitude toward Treating Breakthrough Cancer Pain in Korea / 한국호스피스완화의료학회지

PURPOSE: Adequate control of breakthrough pain is essential for patients with cancer. Managing breakthrough pain mainly depends on understanding the concept of breakthrough pain and the proper usage of rescue medication by physicians. This study aims to assess the attitudes and practice patterns of palliative physicians in managing breakthrough pain for patients in Korea. METHODS: This study was based on data from the 2014 breakthrough cancer pain survey conducted by the Korean Society for Hospice and Palliative Care. One hundred physicians participated in the online survey. Among total 33 self-reported questionnaires, twelve items were selected in this analysis. RESULTS: Rapid onset of action is the main influencing factor in selecting rescue opioids. Oral oxycodone (65%) and parenteral morphine (27%) are commonly used. A few physicians (3%) prefer to use transmucosal fentanyl. The percentage of physicians prescribing oral oxycodone due to its rapid onset of action is just 21.5%, whereas the percentage of physicians using parenteral morphine is 81.5%. Two thirds of respondents (66%) answered that breakthrough pain is not well controlled with rescue medications. CONCLUSION: There is a gap between the needs of physicians in terms of the perceived difficulties of managing breakthrough cancer pain and their practice patterns selecting rescue medications.

Prevalence and characteristics of breakthrough pain in cancer patients: a pilot study

The aim of this study was to clarify the prevalence and characteristics of breakthrough pain in cancer patients. We conducted a cross-sectional survey of consecutive patients older than 20 years of age admitted to a University Hospital with a cancer diagnosis Breakthrough pain was defined as meeting all of the following criteria： Pain 1）with background pain present most of the time, 2）which is well controlled, 3）with short-lived episodes of exacerbation. One hundred and sixty-nine patients were recruited and 118（69.8％）completed the survey. Of these 118 patients, 11％（95％CI：7–18％）had breakthrough pain. Breakthrough pain occurred in 23％（14–35％）of patients with cancer-related pain and 29％（17–45％）of patients with pain from the cancer itself. Patients reported episodes occurring up to three times a day,a time to peak intensity of within 5 minutes, and a duration of untreated episodes of up to 15 minutes are 54％（29–77％）, 54％（29–77％）, 54％（29–77％）, respectively.

A case of impaired consciousness due to fentanyl sublingual tablet overdose

Oral transmucosal fentanyl has been developed for the management of breakthrough pain in cancer patients. Buccal and sublingual fentanyl tablets have been licensed in Japan. However, the optimal use of oral transmucosal fentanyl has not been elucidated. We describe the treatment of cancer‒related pain using a 100μg fentanyl sublingual tablet and a 12.5μg/hr fentanyl patch in a 77 year‒old man with rectal cancer and thoracic vertebral metastasis. After the first use of the fentanyl sublingual tablet, the patient’s consciousness was impaired for 6 hours, however respiration was stable. This case shows that administration of fentanyl sublingual tablets may not be recommended for breakthrough pain incancer patients who are being treated with 30mg/day of oral morphine equivalent dose (20mg/day oxycodone, 12.5μg/hr fentanyl patch).

Breakthrough Cancer Pain / 한국호스피스완화의료학회지

Breakthrough cancer pain is a transient exacerbation of pain that occurs despite relatively well controlled background pain with around-the-clock analgesia. It is highly prevalent in patients with cancer pain, with an overall prevalence of 70~90%. Breakthrough cancer pain has several negative effects on quality of life, including a decrease in functional status and social relationship, and higher incidence of anxiety/depression. It also places a detrimental burden on their families, society, and the healthcare system. According to the pathogenic mechanism, breakthrough cancer pain is classified into two categories: idiopathic (or spontaneous) pain and incident pain. Episodes of breakthrough cancer pain have typical characteristics, including rapid onset (5~10 min), severe intensity, and short duration (30~60 min). However, there are some variations in timing and severity of pain among patients and episodes. Therefore, a thorough assessment of pain episodes is needed and management plan must be individualized to provide optimal treatment. Several immediate-release formulations such as oxycodone, morphine, and hydromorphone are widely used despite relatively slow onset of action. Recent studies have shown that transmucosal fentanyl preparations were effective for faster control of breakthrough pain. We hope to improve management of breakthrough cancer pain with more efficient analgesics in line with currently available evidence.

Pregabalin combined with intrathecal sufentanil infusion for breakthrough pain in patients with bone metastases / 中南大学学报(医学版)

Objective: To evaluate the analgesic effect of pregabalin combined with intrathecal sufentanil infusion for the treatment of breakthrough pain in patients with bone metastases. Methods: A total of 60 breakthrough pain patients with bone metastases were randomly divided to 3 groups: group A (pregabalin combined with intrathecal sufentanil infusion group,n=20), group B (placebo combined with intrathecal sufentanil infusion group,n=20) and group C (oral morphine sulfate controlled-release tablet group,n=20). The differences in visual analogue scale (VAS)between background pain and breakthrough pain, the seizure frequency of breakthrough pain, general satisfaction and side effects of the 3 groups were observed. Results: hTe seizure frequency and VAS of breakthrough pain in group A decreased signiifcantly after the treatment (P<0.05) and the general satisfaction was the best among the the 3 groups (P<0.05), with less nausea and vomiting, constipation, drowsiness and fewer other side effects. Conclusion: Pregabalin combined with intrathecal sufentanil infusion can effectively relieve breakthrough pain in patients with bone metastases.

Factors influencing the treatment effect of cancer pain in patients with moderate and severe chronic pain / 中国肿瘤临床

Objective:This study aimed to analyze the factors affecting the outcome of cancer pain in patients with moderate and severe chronic cancer pain for clinical decision making. Methods: Data were collected from 426 cancer patients with moderate and severe chronic cancer pain, and the factors affecting pain treatment were analyzed. Results:A total of 85.6%of patients had good pain control in 3 days (NRS≤3). Multivariate logistic regression models showed that the pain of patients with bone metastases (P=0.026), breakthrough pain after stable pain control (P0.05). Opioid combination with NSAIDs contributed to easier pain control (P=0.024). Digestive system tumors, pain intensity, limb pain, neuropathic pain, use of transdermal fentanyl matrix patch, multiple metastases in stage-IV patients were suggested to be risk factors of pain control in univariate logistic regression models (P<0.05). Conclusion: Bone metastases, breakthrough pain after pain relief, and high dose of MEDD were independent risk factors. Opioid combination with NSAIDs was a protective factor of pain control.

Efficacy of flurbiprofen axetil for treatment of break-through pain in patients with metastatic bone cancer pain / 中华麻醉学杂志

Objective To evaluate the efficacy of flurbiprofen axetil for treatment of break-through pain (BTP) in patients with metastatic bone cancer pain.Methods Ninety-seven patients with metastatic bone cancer pain complicated with BTP were randomly divided into morphine group (M group,n =51) and flurbiprofen axetil group (F group,n =46).In group M,immediate release morphine sulfate was given orally,and the single dose for pain relief was about 10％ to 15％ of the daily slow-release dose,and the administration was repeated until BTP was relieved.In group F,flurbiprofen axetil 50 mg was infused intravenously over 30 min,and the maximum dose was 150 mg.The BTP frequency was recorded within one month after the first BTP relief.The drug consump-tion for treatment of primary cancer pain,and adverse reaction were recorded.Results The onset time of flurbiprofen axetil and immediate release morphine sulfate was (18± 9) and (35± 11) min,respectively (P ＜ 0.05).The onset time of BTP treatment was significantly shorter,and the incidence of constipation was lower in group F than in group M (P ＜ 0.05).There was no statistical significance in the BTP frequency between the two groups (P ＞ 0.05).As compared with that before BTP treatment,the drug consumption for treatment of primary cancer pain was significantly increased after treatment in group M (P ＜ 0.05) and no significant changes were found after treatment in group F (P ＞ 0.05).Conclusion Flurbiprofen axetil is safer and more effective in relieving BTP in patients with metastatic bone cancer pain than immediate release morphine sulfate,and it does not affect the drug tolerance for treatment of primary pain.

Current research and advances in cancer breakthrough pain / 肿瘤

Although the control of background pain is satisfying, the patients may also suffer from transient exacerbation of pain, which is known as cancer breakthrough pain (BTP). A typical episode of BTP has a fast onset and a short duration. The BTP can apparently affect the quality of life and may also have an adverse impact on healthcare resources. Normal-release oral opioids have been applied in the treatment of cancer BTP, but the late onset and long duration of action of oral opioids may not appropriate for controlling a typical cancer BTP. Some formulations of fentanyl provide more favourable efficacy in the control of cancer BTP, such as oral transmucosal fentanyl citrate (OTFC), buccal fentanyl citrate (FBT), sublingual fentanyl citrate (SLF), and intranasal fentanyl spray (INFS). In addition, some studies have focused on the treatment of cancer BTP with transnasal butorphanol. Copyright© 2011 by TUMOR.