Sublingual Fentanyl Tablets Research Articles

Efficacy, safety, and tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study

Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients.The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8).A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey).Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.

Feasibility of a transmucosal sublingual fentanyl tablet as a procedural pain treatment in colonoscopy patients: a prospective placebo-controlled randomized study

Since patients often experience pain and unpleasantness during a colonoscopy, the present study aimed to evaluate the efficacy and safety of sublingually administered fentanyl tablets for pain treatment. Furthermore, since the use of intravenous drugs significantly increases colonoscopy costs, sublingual tablets could be a cost-effective alternative to intravenous sedation. We conducted a prospective placebo-controlled randomized study of 158 patients to evaluate the analgesic effect of a 100 µg dose of sublingual fentanyl administered before a colonoscopy. Pain, sedation, nausea, and satisfaction were assessed during the colonoscopy by the patients as well as the endoscopists and nurses. Respiratory rate and peripheral arteriolar oxygen saturation were monitored throughout the procedure. There were no differences between the fentanyl and placebo groups in any of the measured variables. The median pain intensity values, as measured using a numerical rating scale, were 4.5 in the fentanyl group and 5 in the placebo group. The sedation and oxygen saturation levels and the respiratory rate did not differ between the groups. The majority of the colonoscopies were completed.Our results indicate that a 100 µg dose of sublingual fentanyl is not beneficial compared to the placebo in the treatment of procedural pain during a colonoscopy.

Therapeutic experience with tramadol for opioid dependence in a patient with chronic low back pain: a case report

BackgroundLong-term opioid treatment for chronic non-cancer pain has become controversial, given the increasing prevalence of opioid dependence. However, there is little information on therapeutic strategies for this condition in Japanese patients. Here, we present a case of successful management of iatrogenic opioid dependence with tramadol in a patient with chronic low back pain.Case presentationA 68-year-old male suffering from intractable low back pain was referred to our pain clinic. He was previously treated in another hospital with transdermal fentanyl patches 6 mg/day and fentanyl sublingual tablets (100 μg as required) for this condition. On the basis of medical examination, including a review of the patient’s medical history, physical examination, X-ray, and his family statement, we diagnosed him with iatrogenic opioid dependence due to inadequate fentanyl use. Then, we developed a treatment plan consisting in fentanyl detoxification with a weak opioid, tramadol. At first, the use of fentanyl sublingual tablets was interrupted after obtaining informed consent. Then, we reduced the dose of transdermal fentanyl 1 mg per 4–5 days replacing with oral sustained-release tramadol. The patient developed mild to moderate withdrawal symptoms during this period, which could be effectively managed by supportive treatments. The hospital psychiatry liaison team continuously provided the patient and his wife with information, counseling, and education regarding the treatment of opioid dependence. Throughout the detoxification process, his reported pain did not exacerbate, even slightly improved over time. The final prescription was sustained-release tramadol 300 mg/day without fentanyl, and his activities of daily living drastically improved. However, unfortunately, he died due to an aortic dissection of stent-graft edge 65 days after surgery.ConclusionsOur case highlighted that sustained-release tramadol could be effectively applied as a detoxification agent for iatrogenic opioid dependence in patients with chronic non-cancer pain.

Effect of Opioid Exposure on Efficacy and Tolerability of Sublingual Fentanyl and Subcutaneous Morphine for Severe Cancer Pain Episodes. Secondary Analysis From a Double-Blind Double-Dummy, Randomized Trial

ContextFew studies have addressed the impact of previous opioid exposure on the effect of opioids for the treatment of severe cancer pain episodes. ObjectivesWe aimed to test whether previous exposure to higher opioid doses was associated with a reduced analgesic effect of fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) and whether it had an influence on their relative effect. MethodsThis is a secondary analysis of a placebo-controlled randomized trial comparing 100 μg FST with 5 mg SCM for the acute treatment of severe cancer pain episodes. The effect of previous opioid exposure (oral morphine equivalent daily dose from 20 to 120 mg) on pain intensity difference (PID) and side effects at 30 and 60 minutes after administration (PID 0–30 minutes, PID 0–60 minutes, and adverse events 30–60 minutes) and on re-medication for inefficacy, was studied by multivariable linear and logistic regression models and statistical tests for interaction. ResultsA total of 114 patients were enrolled. Results indicate modest and nonstatistically significant effect of previous opioid exposure on all the outcomes examined (P = 0.11, P = 0.35, P = 0.07, and P = 0.52, respectively, for PID 0–30 minutes, re-medication, PID 0–60 minutes, and adverse events 30–60 minutes). Nonstatistically significant tests for interaction for all models indicated a lack of impact of previous opioid exposure on the difference in the analgesic effect between treatments. ConclusionIn this study, we could not demonstrate an effect of previous opioid exposure, from 20 to 120 mg oral morphine equivalent daily dose, on the absolute and relative efficacy and tolerability of 100 μg FST and 5 mg SCM for severe cancer pain episodes.

Effects of Age Among Elderly Cancer Patients on Breakthrough Pain Management with Sublingual Fentanyl Tablets.

IntroductionSublingual fentanyl tablets (SFTs) have been shown to be a safe and effective option in controlling breakthrough cancer pain (BTcP). However, further examination is required to investigate the use of SFTs among the elderly. The aim of this study was to examine the influence of age in BTcP management with SFTs in the elderly population.MethodsWe performed subgroup analyses of a recently completed trial in two subsets of individuals: patients aged 65–74 years (low age group) and patients ≥ 75 years (high age group). Pain intensity (PI), onset of pain relief, frequency and duration of BTcP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health status instruments used were the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and the Short Form 12, version 2 (SF-12v2) questionnaire.ResultsLevels of PI at the end of the study improved significantly as compared with baseline in both the low and the high age groups (30.0% and 27.7% reduction, respectively). The onset of analgesia at the end of the study began in < 10 min in 85.0% of young–old subjects and in 62.5% of patients ≥ 75 years, but no significant differences were found. BTcP episodes lasted < 15 min in 75.0% of patients in the low age group and 58.3% in the high age group (p = 0.24). Most of patients in both groups experienced one to five BTcP daily episodes, at all assessment points. HADS-D decreased from 10.78 (± 4.33) to 8.21 (± 3.57) in the low age group, and from 10.96 (± 4.26) to 9.36 (± 3.35) in the high age group (p = 0.02). Significant differences in HADS-A scores from baseline to the end of the study were also observed in both subgroups (p < 0.05). Patients in the low age group had less favorable mental component summary (MCS) and physical component summary (PCS) scores than patients in the high age group. At the end of the study, 10.0% of young–old patients and 29.2% of patients aged ≥ 75 years reported AEs related to their treatment. The most commonly reported AEs included nausea, vomiting, constipation, somnolence, and skin disorders and they were generally mild to moderate in severity.ConclusionsThe results of this study showed that SFTs provided safe and clinically meaningful pain relief in both elderly subgroups. Clinical implications of these findings await validation in large, confirmatory studies to identify age subgroup divergences among elderly cancer patients treated with SFTs.

The efficacy of oral piroxicam fast-dissolving tablets versus sublingual fentanyl in incident breakthrough pain due to bone metastases: a double-blinded randomized study.

Breakthrough pain (BTP) is a transient exacerbation of pain occurring in a patient with chronic, persistent pain. The most common type is incident pain that is mostly related to bone metastases. The oral mucosa is an attractive route for drug delivery. Sublingual fentanyl preparations are a very attractive agent in controlling attacks of BTP due to its rapid absorption through the oral mucosa. Non-steroidal anti-inflammatory drugs (NSAIDs) play a key role as a first step in treatment of cancer pain; piroxicam sublingual formulations could be a useful alternative in controlling incident pain. Our study hypothesis is to evaluate the efficacy of sublingual fentanyl versus oral piroxicam fast-dissolving tablets in patients with incident pain and its impact on functional status. A cohort of 100 adults of both genders suffering from bone metastases. Patients were assigned to receive either sublingual fentanyl tablet (group 1) or oral piroxicam fast-dissolving tablets (group 2). The pain intensity reduction on a 0-10 visual analog scale (VAS), frequency of BTP attacks, and onset of pain relief. Secondary end points included the functional interference items of the Brief Pain Inventory (BPI). There is no significant difference between the two groups regarding the patients' demographics. Significant decline of the VAS in each group in comparison to the pretreatment values (p = 0.001). Non-significant changes of the VAS, duration of pain attacks, and number of rescue doses in comparing both groups were measured. There was significant reduction in group 2 BPI regarding the relation with others, sleep pattern and enjoyment of life parameters at 2 and 4weeks (p = 0.001). Our study demonstrated that oral piroxicam fast-dissolving tablet is an analgesic alternative to sublingual fentanyl in patients with bone metastasis to control incidental BTP attacks with more favorable cost-benefit values.

Correction to: Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain Management According to Cancer Stage and Background Opioid Medication.

In the Original Publication.

Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain Management According to Cancer Stage and Background Opioid Medication.

ObjectiveOur objective was to assess the effect of sublingual fentanyl tablets (SFTs) on pain relief, quality of life, and adverse effects in patients with cancer pain, according to cancer stage and background opioid regimen.MethodsSubgroup analyses from a recently completed study were performed according to cancer stage (locally advanced cancer [LAC] vs. metastatic cancer) and most frequent background opioid medication (fentanyl vs. oxycodone/naloxone). The efficacy and safety of SFTs were evaluated, recording pain intensity (PI), onset of pain relief, and adverse events (AEs). Health status was assessed with the Short Form 12, version 2 (SF-12v2) questionnaire and the Hospital Anxiety and Depression Scale (anxiety subscale [HADS-A] and depression subscale [HADS-D]).ResultsIn total, 54 (67.5%) patients had LAC and 26 (32.5%) had metastatic cancer. The oxycodone/naloxone group included 39 patients (48.1%) and the fentanyl group 29 (35.8%). In all subgroups, pain relief was achieved within 5 min in an increasing number of individuals over time; at the end of the study, PI values decreased (PI-end: 44.4% for LAC vs. 57.9% for metastatic cancer; 44.4% for fentanyl vs. 38.6% for oxycodone/naloxone). HADS and mental component summary (MCS) SF-12v2 scores significantly improved in the LAC group (HADS-A 9.44–8.04; HADS-D 10.46–8.15; MCS 44.69–45.94) and in the fentanyl group (HADS-A 10.05–8.33; HADS-D 11.95–8.76; MCS 44.38–47.19). AEs were reported in few patients and were mostly mild.ConclusionsExploratory subgroup analyses show the efficacy and safety of SFTs for the treatment of breakthrough pain in patients with cancer, regardless of their cancer stage and background opioid medication.

Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.

IntroductionBreakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories.MethodsWe performed age subgroup analyses (<65 and ≥65 years) from a recently completed study conducted in Spain. Pain intensity (PI), onset of pain relief, frequency and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF-12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D).ResultsTwenty-six patients were aged <65 years and 54 were aged ≥65 years. SF-12v2 scores did not enhance significantly from baseline. HADS scores and PI decreased significantly at the end of the study, particularly in younger patients (HADS-A: 19.05 vs. 14.41%; HADS-D: 21.35 vs. 18.57%; PI: 67.23 vs. 56.30%). Onset of analgesia began in 2–5 min in 63.3% of subjects aged <65 years and in 36.4% of subjects aged >65 years. Most patients experienced one to five daily episodes after 30 days, and <5% needed a treatment change. AEs were less frequently reported in older individuals (20.5 vs. 36.4%).ConclusionAge subgroup analyses suggest that SFTs are an effective and safe treatment for the management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated and efficient option to control cancer BTP in the elderly.

Fentanyl Sublingual Tablets Versus Subcutaneous Morphine for the Management of Severe Cancer Pain Episodes in Patients Receiving Opioid Treatment: A Double-Blind, Randomized, Noninferiority Trial.

Purpose Fentanyl sublingual tablets (FST) are a potentially useful alternative to parenteral opioids such as subcutaneous morphine (SCM) to treat severe cancer pain episodes. No direct comparison between FST and SCM is available. The aim of this study was to test noninferiority of FST versus SCM during the first 30 min postadministration. Methods Patients receiving stable opioid therapy and experiencing a severe pain episode were randomly assigned to either 100 µg FST or 5 mg SCM in a double-blind, double-dummy trial. Average pain intensity (PI) assessed on a 0 to 10 numerical rating scale at 10, 20, and 30 min postadministration was the main end point. Analysis of covariance, adjusted by baseline PI, was the main analysis. The noninferiority margin (NIm) for the between-group difference was set at -0.6, that is, equal to one third of the minimum clinically important PI difference of two points. Results A total of 114 patients were randomly assigned to either FST (n = 58) or SCM (n = 56). One patient (in the FST group) withdrew consent before drug administration and was excluded from analysis. Baseline mean PIs were 7.5 in both groups; mean average PIs assessed at 10, 20, and 30 min postadministration were 5.0 and 4.5 for FST and SCM, respectively, with the 95% CI of the between-group difference including the NIm (-0.49; 95% CI, -1.10 to 0.09). Patients taking FST received a second drug dose after 30 min more frequently than did patients taking SCM (51% v 37%, respectively; risk difference, -13%; 95% CI, -30% to 3%). Both treatments were well tolerated, with average follow-up adverse event scores below the response of "A Little." Ninety-three percent of patients preferred the sublingual administration. Conclusion This trial did not show noninferiority of FST versus SCM within the chosen NIm. Both treatments were safe, and patients preferred the sublingual route of administration. FST provides analgesia with modest to moderate increased risk of lower efficacy compared with SCM.

フェンタニル舌下錠の適正使用に向けた現状調査と問題点の検討

目的：フェンタニル舌下錠（Fentanyl Sublingual Tablets：FST）の有用性および安全性について調査を行い，FSTの適正使用に向けた問題点について検討した．

Erratum to: Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes.

Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30 days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. Of the 102 patients considered eligible, 81 (79.4 %) were enrolled; of these, 69 (85.1 %) completed the study. Significant pain reduction was achieved for average PI (p < 0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p = 0.005) and the anxiety subscale (p < 0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p < 0.001) and the physical component score (p = 0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.

Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes.

Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. Of the 102 patients considered eligible, 81 (79.4%) were enrolled; of these, 69 (85.1%) completed the study. Significant pain reduction was achieved for average PI (p<0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p=0.005) and the anxiety subscale (p<0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p<0.001) and the physical component score (p=0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.

Gasto económico del tratamiento del dolor irruptivo

This article presents two pharmacoeconomic studies comparing the compressedfentanyl lozengewith an integral oromucosalapplicator (Actiq®); fentanyl sublingual tablets(Abstral®); effervescent fentanyl buccal tablets(Effentora®) and nasal fentanyl with two technologies: a formulation that contains pectin in a gel-based nasal spray (PecFent®) and another formulation in an aqueous solution without pectin (Instanyl®). The first of these studies aimed to analyze the potential savings due to the progressive introduction of fentanyl pectin nasal spray for the treatment of adult patients with breakthrough cancer pain. The second study aimed to determine the effectiveness and efficiency of fentanyl pectin nasal spray compared with the other tansmucosal treatments currently on the market. The first study showed a reduction in healthcare costs with the progressive introduction of fentanyl pectin nasal spray for the treatment of breakthrough pain in the publicly-funded health system in Spain. The second study showed that the most efficient option (greatest effectiveness and lowest cost) in all the cases analyzed was the fentanyl-pectin nasal spray.

Efficacy and Safety of Sublingual Fentanyl Tablets for the Management of Breakthrough Pain in Patients with Chronic Musculoskeletal Pain with Neuropathic Component: Multicenter Prospective Study

Despite its prevalence and impact, breakthrough pain (BTP) in chronic non-cancer pain with neuropathic component, has not been well studied and is sometimes unrecognized and often undertreated. We evaluated the efficacy of sublingual fentanyl tablet (SLF) for the treatment of BTP in opioid-tolerant patients with chronic musculoskeletal pain with neuropathic component in terms of relief of pain intensity and assessed whether hypothetical pain relief impacts on quality of life (QoL). A multicenter, prospective, open-label study was conducted over a 30-day period. Efficacy was evaluated using a visual analogue scale (VAS) and time to onset of action of SLF. The incidence of dependence was assessed by the Leeds Dependence Questionnaire (LDQ). Changes in QoL were evaluated using the Brief Pain Questionnaire (BPI) and the EuroQol (EQ-5D). Adverse events (AE) were recorded throughout. 106 patients were enrolled and 105 completed the study. The average pain reduction across the study was -3.30 points [95 % confidence interval (CI) 2.9-3.7; P < 0.0001]. Pain intensity improvement from baseline was statistically significant at first assessment and all subsequent assessments (P < 0.0001). The most common AEs included nausea (33.87 %), constipation (33.06 %), somnolence (19.35 %) and vomiting (6.45 %). No significant differences were observed on LDQ (P = 0.71). QoL as measured by BPI showed statistically significant improvement in all four severity items and all interference items (P < 0.0001) and a significant improvement in the percentage of pain relief reported by patients (P < 0.0001). EQ-5D results showed a trend towards improvement. Mean self-rate health status, as measured by the EQ VAS scale increased significantly (P < 0.0001). SLF provides significant reductions in BTP intensity. The results of the BPI and EQ-5D assessments indicate that pain relief is associated with improvement of functioning and enhancement of QoL.

フェンタニル舌下錠使用時の留意点と院内スタッフへの周知─ライセンス制と網羅的院内勉強会の導入

フェンタニル舌下錠使用時の留意点と院内スタッフへの周知─ライセンス制と網羅的院内勉強会の導入

Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain.

BackgroundThe purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP) in Spain.MethodsA 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal). Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.ResultsPatients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in the total costs of BTcP over the next 4 years. Results of the sensitivity analysis showed that the model was most sensitive to drug cost per day for the fentanyl buccal tablet. A 50% decrease in the daily cost of the fentanyl buccal tablet resulted in the largest overall decrease in budget impact of €5.4 million.ConclusionThe increase in use of the fentanyl buccal tablet leads to overall savings in the budget impact for the Spanish National Health System. Although the economic impact of treatment for BTcP was shown to increase over 4 years due to population growth, the average annual cost per patient was reduced by €29 with increased use of the fentanyl buccal tablet.

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

IntroductionBreakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients.MethodsThis was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral®, Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel.ResultsDisintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age.ConclusionSublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-013-0019-6) contains supplementary material, which is available to authorized users.

Letter to the Editor: Trauma pain - a military perspective.

We read with interest the article on the military perspective of trauma pain.1 We agree that the dose and the intramuscular route of the morphine autojet is suboptimal for patients in shock who require analgesia.2 Either fentanyl or ketamine would be a more suitable alternative. The fentanyl lozenge has been in military use since the early 1990s, and there are reports of soldiers biting and swallowing the contents of the lozenge. The UK military has chosen the 400 µg dose, but interestingly the US military has opted for the 800 µg dose.3 In 2012 the Danes opted for intranasal fentanyl (Instanyl®) based on the experience of their civilian ambulance service (personal communication with Dr S. Trautner, Senior Medical Officer, Falck Ambulance Services, Denmark). We feel that fentanyl is potentially better administered via the intranasal or the sublingual/buccal route than as a lozenge. Whatever the pre-hospital analgesia choice(s), education of the provider must include clinical observation of these analgesic approaches. At our hospital we have a long tradition of military paramedics being placed on clinical attachments. They are shown how ketamine in 10- to 20-mg boluses administered intravenously or sublingual fentanyl tablets (Abstral®) can be used safely for painful procedures at the regional burns centre. For medical officers, the benefits of rapid analgesia by combining morphine (10 mg) and alfentanyl (1 mg) have been seen in the recovery unit.4 The biggest difference between civilian and military hospital practice is the early use by the military of co-analgesics5 (amitriptyline and pregabalin) for high-risk neuropathic pain conditions such as amputations, burns,6 plexus or nerve injuries. In the pain clinic, we treat both veterans and serving members of the military. Although there is a particular military perception regarding everyday aches and pains, it cannot always be generalised to the trauma patient. We have observed that soldiers will recall with great detail their memories of the time leading up to and following injury. They can vividly remember the kindness or cruelty of the people around them along their journey. A recurring theme is the failure to relieve thirst and/or pain. The importance of early aggressive analgesia is emphasised on the Battlefield Advanced Trauma Life Support (BATLS) course, provided there is C>ABC stability.7 The emphasis should be on not only drugs but also non-drug approaches such as reassurance, distraction, elevation, splintage and cling film (for burns). Early pain relief also addresses the psychosocial complications of traumatic injury. Holbrook et al.8 have shown a reduction in perceived pain levels with morphine or other opiates, which may also lower the rate of post-traumatic stress disorder onset after major military trauma. The best advice for civilian doctors with no military experience would be to read the excellent article by Gauntlett-Gilbert and Wilson in the same issue.9 It highlights the differences between military and civilian populations and provides a useful history-taking checklist. Future publications should include outcome measures, otherwise we run the risk of basing our responses on misleading sound bites rather than sound statistics.10

Evidence-Based Treatment of Cancer-Related Breakthrough Pain With Opioids

Opioids are considered important analgesics in the treatment armamentarium for moderate-to-severe background cancer pain. The past decade has seen clinical trials of transmucosal opioid formulations for breakthrough pain in cancer (BTPc), beginning with oral transmucosal fentanyl citrate (OTFC), followed by fentanyl buccal tablet and intranasal fentanyl spray, and most recently sublingual fentanyl tablet, fentanyl buccal soluble film, and fentanyl pectin nasal spray. During that time, enough rigorous evidence has accumulated to support the development of recommendations on treating BTPc with transmucosal formulations. This article describes the randomized controlled trials that have led to the support of the use of transmucosal fentanyl therapies for BTPc, starting in 1999 with OTFC formulations through to the end of 2011. Although oral opioids have been used for historical reasons, evidence supports the use of intravenous morphine or transmucosal fentanyl for treating BTPc, regardless of the opioid being taken to manage background pain. Furthermore, most studies have found no meaningful relationship between the effective dose of transmucosal opioid and the around-the-clock scheduled medication nor the previous rescue medication. The accumulated evidence shows that transmucosal fentanyl formulations provide a rapid effect on BTPc, with adverse events typical of opioids.