Oral Transmucosal Fentanyl Citrate Research Articles

Oral transmucosal fentanyl citrate as breakthrough pain relieving medication: A pilot study

ABSTRACT Background: Breakthrough pain in cancer patients is a common and distressing symptom that significantly impacts their quality of life. Traditional pain management strategies often fail to provide adequate relief. Oral transmucosal fentanyl citrate (OTFC) has emerged as a rapid-onset opioid analgesic, offering a potential solution for managing this challenging condition in home care settings. Aims: This study aims to evaluate the efficacy of OTFC in managing breakthrough pain and its effects on the quality of life in cancer patients treated at home. Materials and Methods: A pilot study was conducted with 40 cancer patients experiencing more than one episode of breakthrough pain daily. These patients were administered OTFC 400 μg for pain management. Degree of pain (NRS) and modified ‘Quality of Well-being’ (QWB) scores were analysed using data filled in by patients. Data were collected and analysed using paired t-tests to compare pre- and post-treatment scores. Results: The administration of OTFC resulted in a significant reduction in pain, as indicated by the decrease in NRS scores from 9.9 ± 0.304 to 0.5 ± 0.906 within 30 minutes (P < 0.0001). Additionally, there was a marked improvement in QWB scores, which increased from 26.18 ± 2.8 to 36.3 ± 3.16 over the same period (P < 0.001). Mild side effects, such as nausea, headache, and somnolence, were reported, but no serious adverse events were observed. Conclusions: We conclude that OTFC 400 μg is an effective and well-tolerated option for managing breakthrough pain in cancer patients and in improving the quality of life in home care settings.

Deployed Combat Use of Methoxyflurane for Analgesia.

The U.S. Military needs fast-acting, non-opioid solutions for battlefield pain. The U.S. Military recently used morphine auto-injectors, which are now unavailable. Off-label ketamine and oral transmucosal fentanyl citrate use introduces challenges and is therefore uncommon among conventional forces. Sublingual suftentanil is the only recent pain medication acquired to fill this gap. Conversely, methoxyflurane delivered by a handheld inhaler is promising, fast-acting, and available to some partner forces. We describe methoxyflurane use reported in the Department of Defense Trauma Registry (DODTR). We requested all available DODTR encounters from 2007 to 2023 with a documented intervention or assessment within the first 72 hours of care. We analyzed casualties who received methoxyflurane in the prehospital setting using descriptive statistics. There were 22 encounters with documented methoxyflurane administration. The median patient age was 23 (range 21-31) years. All were men. The largest proportion was partner force (50%), followed by U.S. Military (27%). Most (64%) sustained battle injuries. Explosives were the most common mechanism of injury (46%), followed by firearms (23%). The median injury severity score was 5 (range 1-17). The most frequent injuries were serious injuries to the extremities (27%), and 23% of patients (5) received a tourniquet. One-half of the casualties received concomitant pain medications. Only three casualties had multiple pain scores measured, with a median pain score change of -3 on a scale of 10. Methoxyflurane use in deployed combat shows both feasibility and usability for analgesia.

Oral transmucosal fentanyl citrate analgesia in prehospital trauma care: an observational cohort study

BackgroundPain is one of the major prehospital symptoms in trauma patients and requires prompt management. Recent studies have reported insufficient analgesia after prehospital treatment in up to 43% of trauma patients, leaving significant room for improvement. Good evidence exists for prehospital use of oral transmucosal fentanyl citrate (OTFC) in the military setting. We hypothesized that the use of OTFC for trauma patients in remote and challenging environment is feasible, efficient, safe, and might be an alternative to nasal and intravenous applications.MethodsThis observational cohort study examined 177 patients who were treated with oral transmucosal fentanyl citrate by EMS providers in three ski and bike resorts in Switzerland. All EMS providers had previously been trained in administration of the drug and handling of potential adverse events.ResultsOTFC caused a statistically significant and clinically relevant decrease in the level of pain by a median of 3 (IQR 2 to 4) in NRS units (P < 0.0001). Multiple linear regression analysis showed a significant absolute reduction in pain, with no differences in all age groups and between genders. No major adverse events were observed.ConclusionsPrehospital administration of OTFC is safe, easy, and efficient for extrication and transport across all age groups, gender, and types of injuries in alpine environments. Side effects were few and mild. This could provide a valuable alternative in trauma patients with severe pain, without the delay of inserting an intravenous line, especially in remote areas, where fast action and easy administration are important.

The Saunders report into the Manchester arena attack

Journal of Paramedic PracticeVol. 14, No. 12 CommentaryThe Saunders report into the Manchester arena attackTom MallinsonTom MallinsonEmail:E-mail Address: [email protected]Lecturer, College of Remote and Offshore Medicine, MaltaSearch for more papers by this authorTom MallinsonPublished Online:6 Dec 2022https://doi.org/10.12968/jpar.2022.14.12.490AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Aldington D, Jagdish S. The fentanyl ‘lozenge’ story: from books to battlefield. J R Army Med Corps. 2014;160(2):102–104. https://doi.org/10.1136/jramc-2013-000227 Crossref, Google ScholarCarenzo L, McDonald A, Grier G. Pre-hospital oral transmucosal fentanyl citrate for trauma analgesia: preliminary experience and implications for civilian mass casualty response. Br J Anaesth. 2022;128(2):e206–e208. https://doi.org/10.1016/j.bja.2021.08.017 Crossref, Google ScholarEllerton JA, Greene M, Paal P. The use of analgesia in mountain rescue casualties with moderate or severe pain. Emerg Med J. 2013;30(6):501–505. https://doi.org/10.1136/emermed-2012-202291 Crossref, Google ScholarEvents Industry Forum. The purple guide to health, safety and welfare at music and other events. 2022. https://www.thepurpleguide.co.uk (accessed 24 November 2022) Google ScholarGrassin-Delyle S, Shakur-Still H, Picetti R et al.. Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial. Br J Anaesth. 2021;126(1):201–209. https://doi.org/10.1016/j.bja.2020.07.058 Crossref, Google ScholarJESIP. Working Together, Saving Lives. 2022. https://www.jesip.org.uk/ (accessed 28 November 2022) Google ScholarManchester Arena Inquiry. Volume 2: emergency response. 2022. https://manchesterarenainquiry.org.uk/report-volume-two (accessed 24 November 2022) Google ScholarNational Ambulance Resilience Unit. National Amnulance Resilience Unit: Preparing for the future, protecting lives today.. 2022, https://naru.org.uk/ (accessed 28 November 2022) Google ScholarOakeshott JE, Griggs JE, Wareham GM, Lyon RM; Kent Surrey Sussex Air Ambulance Trust. Feasibility of prehospital freeze-dried plasma administration in a UK helicopter emergency medical service. Eur J Emerg Med. 2019;26(5):373–378. https://doi.org/10.1097/MEJ.0000000000000585 Crossref, Google ScholarPark CL, Langlois M, Smith ER et al.. How to stop the dying, as well as the killing, in a terrorist attack. BMJ. 2020;368:m298. https://doi.org/10.1136/bmj.m298 Crossref, Google ScholarVassallo J, Moran CG, Cowburn P, Smith J. New NHS prehospital major incident triage tool: from MIMMS to MITT. Emerg Med J. 2022;39(11):800–802. https://doi.org/10.1136/emermed-2022-212569 Crossref, Google Scholar FiguresReferencesRelatedDetails 2 December 2022Volume 14Issue 12ISSN (print): 1759-1376ISSN (online): 2041-9457 Metrics History Published online 6 December 2022 Published in print 2 December 2022 Information© MA Healthcare LimitedPDF download

Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way Crossover Study in 24 Healthy Volunteers.

Background For more than 60 years, the synthetic opioid fentanyl has been widely used in anaesthesia and analgesia. While the intravenous formulation is primarily used for general anaesthesia and intensive care settings, the drug's high lipophilic properties also allow various noninvasive routes of administration. Published data suggest that intranasal administration is also attractive for use as intranasal patient-controlled analgesia (PCA). A newly developed intranasal fentanyl formulation containing 47 μg fentanyl, intravenous fentanyl, and oral transmucosal fentanyl citrate were characterised, and bioavailability was compared to assess the suitability of the intranasal formulation for an intranasal PCA product. Methods 27 healthy volunteers were enrolled in a single-centre, open-label, randomised (order of treatments), single-dose study in a three-period crossover design. The pharmacokinetics of one intranasal puff of fentanyl formulation (47 μg, 140 mL per puff), one short intravenous infusion of 50 μg fentanyl, and one lozenge with an integrated applicator (200 μg fentanyl) were studied, and bioavailability was calculated. Blood samples were collected over 12 hours, and plasma concentrations of fentanyl were determined by HPLC with MS/MS detection. Results 24 volunteers completed the study. The geometric mean of AUC0-tlast was the highest with oral transmucosal administration (1106 h ∗ pg/ml, CV% = 32.86), followed by intravenous (672 h ∗ pg/ml, CV% = 32.18) and intranasal administration (515 h ∗ pg/ml, CV% = 30.10). Cmax was 886 pg/ml (CV% = 59.38) for intravenous, 338 pg/ml (CV% = 45.61) for intranasal, and 310 pg/ml (CV% = 29.58) for oral transmucosal administration. tmax was shortest for intravenous administration (0.06 h, SD = 0.056), followed by intranasal (0.21 h, SD = 0.078) and oral transmucosal administration (1.20 h, SD = 0.763). Dose-adjusted absolute bioavailability was determined to be 74.70% for the intranasal formulation and 41.25% for the oral transmucosal product. In total, 38 adverse events (AEs) occurred. Fourteen AEs were potentially related to the investigational items. No serious AE occurred. Conclusion Pharmacokinetic parameters and bioavailability of the investigated intranasal fentanyl indicated suitability for its intended use as an intranasal PCA option.

The Newest Battlefield Opioid, Sublingual Sufentanil: A Proposal to Refine Opioid Usage in the U.S. Military

There is an ongoing opioid epidemic in the USA, and the U.S. military is not immune to the health threat. To combat the epidemic, the Department of Defense (DoD) and Department of Veterans' Affairs (DVA) issued new clinical practice guidelines and launched the Opioid Safety Initiative aimed at reducing opioid prescriptions. Furthermore, the DoD continually refined opioid protocols for acute pain on the battlefield, evolving from intramuscular morphine to intravenous morphine administration to oral transmucosal fentanyl citrate lollipops (Actiq) to finally sublingual sufentanil tablets (SSTs, Dsuvia). Interestingly, the newest introduction of SSTs into the military sparked great controversy, as there are concerns over the drug's potential for misuse. However, although the opioid crisis may understandably foster an aversion to new candidate opioids, the therapeutic benefits of effective opioids in acute trauma settings should not be overlooked. SSTs may offer an improved analgesic option to meet the battlefield's unmet needs with its non-invasive, sublingual delivery system and favorable pharmacologic properties that mitigate the risk for side effects, addiction, and adverse outcomes. Accordingly, this commentary aims to (1) review the evolution of opioid use on the battlefield and discuss the medical benefits and limitations of SSTs in acute trauma settings, (2) highlight the importance of chronic pain management post-deployment through evidence-based non-opioid modalities, and (3) explore avenues of future research. Ultimately, we propose that SSTs are an important improvement from existing battlefield opioids and that refining, not abandoning, opioid usage will be key to effectively managing pain in the military.

Trends in prehospital pain management following the introduction of new clinical practice guidelines.

Early pain treatment following injury has been shown to improve long-term outcomes, while untreated pain can facilitate higher posttraumatic stress disorder rates and worsen outcomes. Nonetheless, trauma casualties frequently receive inadequate analgesia. In June 2013, a new clinical practice guideline (CPG) regarding pain management was introduced in the Israel Defense Forces (IDF) Medical Corps, recommending oral transmucosal fentanyl citrate (OTFC) and low-dose intravenous (IV)/intramuscular ketamine. The purpose of this study was to examine trends in prehospital pain management in the IDF. All cases documented in the IDF trauma registry between 2008 and 2020 were examined. This study compared casualty parameters before and after the introduction of analgesia CPG in 2013. Parameters compared included demographics, injury parameters, treatment modalities, and types of analgesia provided. Overall, 5,653 casualties were included in our study. During the 6 years before the introduction of the CPG, 289 (26.7%) of 1,084 casualties received an analgesic treatment, compared with 1,578 (34.5%) of 4,569 casualties during the 7 years following (p < 0.001). Since its introduction, OTFC was administered to 41.8% of all casualties who received analgesia and became the most used analgesic drug in 2020 (61.1% of casualties receiving analgesia). The rate of IV morphine significantly decreased after 2013 (22.6-16%, p < 0.001). Pain management has become more common in trauma patients' prehospital care in the IDF in recent years. There has been a significant increase in analgesia administration, with the increased use of OTFC, along with a significant reduction in the use of IV morphine. These results may be attributed to introducing a pain management CPG and implementing OTFC among medical teams. The perception of OTFC as a safe user-friendly analgesic may have contributed to its use by medical providers, increasing analgesia rates overall. Therapeutic/care management, level III.

The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

The Efficacy of Meperidine for Pain Management in Orthopedic, Dental, and General Surgery in Children: A Review Study

Background: The present study aimed to assess the efficacy of Meperidine for pain relief in children after orthopedic, abdominal surgery, and laceration repair. Materials and Methods: A systematic serch was performed using the following online databases: Medline, Cochrane, Web of Science, Scopus, and Embase to 2 June 2020, with keywords: (Meperidine OR Pethidine) AND (Pain) AND (Child OR Children) with no language restriction. Results: The Acetaminophen had slightly higher pain scores compared to Meperidine after dental restoration among children. There was better sedation along with more rapid onset and recovery in the combined regimens of Atropine/Midazolam/Ketamine compared to Meperidine/Midazolam. Two studies reported the superiority of Morphine over Meperidine for pain management. A study found a significant increase in the mean pediatric pain scores in the Tramadol group compared to the Meperidine group after 24 hours. There was no difference in the Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) between MPC (Meperidine/Promethazine/Chlorpromazine), and OTFC (Oral Transmucosal Fentanyl Citrate) groups during the laceration repair. In the study on the incidence of sleep on the way home or shortly after arriving at home, there were differences in chloral hydrate, Meperidine, and Hydroxyzine regimen compared to Midazolam alone among children being sedated during endodontic procedures. Conclusion: Meperidine was effective for controlling pain in orthopedic, abdominal surgery, laceration repair, and dental restoration. However, it was only superior to the Tramadol group. Regarding dental surgery, a combination regimen were more effective compared to single Midazolam. The pain intensity during early recovery was slightly lower in Meperidine group. The regimen had better sedation with more rapid onset and recovery compared to Meperidine/Midazolam.

Trends in Prehospital Analgesia Administration by US Forces From 2007 Through 2016

Background: Tactical Combat Casualty Care (TCCC) guidelines regarding prehospital analgesia agents have evolved. The guidelines stopped recommending intramuscular (IM) morphine in 1996, recommending only intravenous (IV) routes. In 2006, the guidelines recommended oral transmucosal fentanyl citrate (OTFC), and in 2012 it added ketamine via all routes. It remains unclear to what extent prehospital analgesia administered on the battlefield adheres to these guidelines. We seek to describe trends in analgesia administration patterns on the battlefield during 2007–2016.Methods: This is a secondary analysis of a Department of Defense Trauma Registry data set from January 2007 to August 2016. Within that group, we searched for subjects who received IM morphine, IV morphine, OTFC, parenteral fentanyl, or ketamine (all routes).Results: Our predefined ED search codes captured 28,222 subjects during the study period. Of these, 594 (2.1%) received IM morphine; 3,765 (13.3%) received IV morphine; 589 (2.1%) received OTFC; and 1,510 (5.4%) subjects received ketamine. Annual rates of administration of IM morphine were relatively stable during the study period, while those for OTFC and ketamine generally trended upward starting in 2012. In particular, the proportion of subjects receiving ketamine rose from 3.9% (n = 995/25,618) during the study period preceding its addition to the TCCC guidelines (2007 to 2012) to 19.8% thereafter (2013–2016, n = 515/2,604, p < 0.001).Conclusions: During the study period, rates of prehospital administration of IM morphine remained relatively stable while those for OTFC and ketamine both rose. These findings suggest that TCCC guidelines recommending the use of these agents had a material impact on prehospital analgesia patterns.

A Survey of Wilderness Medicine Analgesia Practice Patterns

In 2014, the Wilderness Medical Society (WMS) published guidelines for the treatment of acute pain in remote settings. We surveyed wilderness medicine providers on self-reported analgesia prescribing practices. We conducted a prospective, anonymous survey. Respondents were recruited from the WMS annual symposium in 2016. All willing attendees were included. During the symposium, we collected a total of 124 surveys (68% response rate). Respondent age was 42±12 (24-79) years (mean±SD with range), 58% were male, and 69% reported physician-level training. All respondents had medical training of varying levels. Of the physicians reporting a specialty, emergency medicine (59%, n=51), family medicine (13%, n=11), and internal medicine (8%, n=7) were reported most frequently. Eighty-one (65%) respondents indicated they prefer a standardized pain assessment tool, with the 10-point numerical rating scale being the most common (54%, n=67). Most participants reported preferring oral acetaminophen (81%, n=101) or nonsteroidal anti-inflammatory drugs (NSAID) (91%, n=113). Of those preferring NSAID, most reported administering acetaminophen as an adjunct (82%, n=101). Ibuprofen was the most frequently cited NSAID (71%, n=88). Of respondents who preferred opioids, the most frequently preferred opioid was oxycodone (26%, n=32); a lower proportion of respondents reported preferring oral transmucosal fentanyl citrate (9%, n=11). Twenty-five (20%, n=25) respondents preferred ketamine. Wilderness medicine practitioners prefer analgesic agents recommended by the WMS for the treatment of acute pain. Respondents most frequently preferred acetaminophen and NSAIDs.

Clinical rationale for administering fentanyl to cancer pain patients: Two Delphi surveys of pain management experts in Denmark

To describe the rationale behind the choice of fentanyl administration forms as reported by Danish nurses and physicians specializing in pain management. Sixty nurses and 60 physicians specializing in pain management in Denmark were contacted via an Internet survey system to perform two Delphi surveys. In the brainstorming phase, the main reasons for administering and not administering fentanyl patches and oral transmucosal fentanyl citrate (OTFC) were identified. In the second phase, the nursing and medical experts rated the importance of these reasons on an 11-point Numerical Rating Scale. Responses from 10 pain nurses and 14 pain doctors were used for the final analysis. Impossible or difficult oral intake of analgesia was the most important reason to administer fenantyl patches, whereas patients' dermatological problems and neuropathic pain origin were the most important reasons for not administering fenantyl patches in both panels. OTFC was presented as an alternative or second choice administration form for breakthrough cancer pain by both nurses and doctors. A damaged mouth, the high cost, and energy required for administration of this medication were reported as the main reasons why OTFC was only rarely prescribed to cancer pain patients in Denmark. The reasons for administering fentanyl in different administration forms reported by Danish pain nurses and pain specialists partly differed from those derived from the literature. Studies of pain management traditions could improve the understanding of the reasons for analgesic administration.

Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naïve patients with severe chronic noncancer pain

Chronic noncancer pain is often undertreated. To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain. A total of 215 patients with chronic (> or =6 months), severe (VAS > or = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 microg/h fentanyl TTS was titrated in 25 microg/h increments to a visual analog scale (VAS) score < or = 4. OTFC was administered as single-unit doses of 400 microg. The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 microg/h dose in 48 percent of patients, the 75 microg/h dose in 18 percent, and the 100 microg/h dose in 5 percent (only two patients required >100 microg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two. Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain.

Prehospital Interventions During Mass-Casualty Events in Afghanistan: A Case Analysis.

Mass-casualty (MASCAL) events are known to occur in the combat setting. There are very limited data at this time from the Joint Theater (Iraq and Afghanistan) wars specific to MASCAL events. The purpose of this report was to provide preliminary data for the development of prehospital planning and guidelines. Cases were identified using the Department of Defense (DoD; Virginia USA) Trauma Registry (DoDTR) and the Prehospital Trauma Registry (PHTR). These cases were identified as part of a research study evaluating Tactical Combat Casualty Care (TCCC) guidelines. Cases that were designated as or associated with denoted MASCAL events were included. Data Fifty subjects were identified during the course of this project. Explosives were the most common cause of injuries. There was a wide range of vital signs. Tourniquet placement and pressure dressings were the most common interventions, followed by analgesia administration. Oral transmucosal fentanyl citrate (OTFC) was the most common parenteral analgesic drug administered. Most were evacuated as "routine." Follow-up data were available for 36 of the subjects and 97% were discharged alive. The most common prehospital interventions were tourniquet and pressure dressing hemorrhage control, along with pain medication administration. Larger data sets are needed to guide development of MASCAL in-theater clinical practice guidelines. Schauer SG , April MD , Simon E , Maddry JK , Carter R III , Delorenzo RA . Prehospital interventions during mass-casualty events in Afghanistan: a case analysis. Prehosp Disaster Med. 2017;32(4):465-468.

Efficacy of Oral Transmucosal Fentanyl Citrate for Premedication in Patients for Surgery under General Anesthesia.

Background:Oral transmucosal fentanyl citrate (OTFC), a water soluble salt when mixed in saliva is 80% nonionized; making it the only opioid suitable for transmucosal absorption. OTFC has rapid onset of action (3–5 min) with peak effect at 20–40 min and total duration of activity is 2–3 h.Aims:This study aims to determine the efficacy of OTFC as premedicant in patients scheduled for surgery under general anesthesia (GA) and to assess the effects of OTFC on anxiety, sedation.Settings and Design:A prospective randomized study.Subjects and Methods:Patients between 21 and 60 years of age in American Society of Anesthesiologists physical status Classes I and II scheduled for elective surgery under GA were randomly assigned to three groups of 30 each: OTFC, placebo, and control. Mean arterial blood pressure (MAP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) along with anxiety and sedation scores were recorded as baseline and upon entering the operation theater. Adverse effects were also recorded.Statistical Analysis Used:Statistical analysis was done using Statistical Package for Social Sciences Version 15.0 Statistical Analysis Software.Results:No significant differences were found in MAP, HR, RR, or SpO2 among the groups. OTFC group demonstrated significantly higher levels of anxiolysis than the control group (P < 0.05). No significant difference in sedation score was found. No remarkable adverse effects were observed.Conclusions:OTFC is an effective anxiolytic in adult with minimal risks and side effects. It is readily acceptable by the patients in its given form.

Effect of Modulated Electrohyperthermia on the Pharmacokinetics of Oral Transmucosal Fentanyl Citrate in Healthy Volunteers

PurposeThis study aimed to determine whether changes occur in fentanyl absorption and disposition when administered in conjunction with modulated electrohyperthermia (mEHT) treatment. MethodsA randomized, single-dose, crossover, open-label study was used to investigate the effect of mEHT on the pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing. FindingsGeometric mean ratios (ratio of fentanyl with mEHT to fentanyl alone) for the Cmax and AUC0–last were 1.20 (90% CI, 1.09–1.32) and 1.15 (90% CI, 0.99–1.33), respectively. The mean temperature of the abdominal skin surface increased by approximately 4°C. ImplicationsThere was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with mEHT, and it is not necessary to modify the dosing regimen. cris.nih.go,kr Identifier: KCT0001286.

Comparing the effectiveness of intranasal fentanyl spray with oral transmucosal fentanyl citrate in breakthrough pain

Breakthrough cancer pain (BTCP) is complex and severe, affecting quality of life and increasing hospitalisation. BTCP has a rapid onset that requires fast acting medication with minimal side effects. This article compares the effectiveness of intranasal fentanyl spray (INFS) and oral transmucosal fentanyl citrate (OTFC) and their alleviation of BTCP within 10 minutes of administration. The article considers pharmacokinetic and bioavailability studies demonstrating the efficacy of the route of administration, time-based effects of pain relief as well as patient preference. The data collected indicates that INFS is more effective than OTFC for BTCP.

Manejo de opioides para el dolor basal e irruptivo oncológico

Cancer-related pain is experienced by 90% of patients with cancer. The mainstays of treatment are opioids and the World Health Organization's analgesic ladder. Breakthrough cancer pain (BCP) is a form of cancer-related pain that is particularly difficult to manage with classical opioids. In this review, we discuss titration and opioid rotation in both background and breakthrough pain. We also review the contribution of fast-acting fentanyl preparations for the treatment of BCP and its indications and dose titration. The first drugs developed specifically for the treatment of BCP were oral transmucosal fentanyl citrate (CFOT) and fentanyl buccal tablets. Because oral fentanyl administration is not an option in many cancer patients, the development of a fentanyl nasal spray (FNS) has emerged as a more effective method of administration.

Treatment with ketamine mouthwashes with and without transmucosal fentanyl in major opiate-resistant orofacial cancer pain

PurposeThe objective of this study was to determine if an oral ketamine mouth wash and expectorant, that may or may not rinse transmucosal fentanyl, was a safe and effective method to alleviate a series of various difficult to control orofacial pain of cancer origin. Materials and methodsA prospective review was made of the medical charts of 20 patients, finding 8 patients who received ketamine mouthwash (40mg=4ml), 8 patients who received ketamine mouthwash and oral transmucosal fentanyl citrate 200mcg, and 4 patients with systemic opioids for refractory orofacial and mucositis pain. ResultsOf the 20 patients, 16 had orofacial or mucositis pain refractory to a mixture of lidocaine and opioids. The effectiveness of ketamine mouthwash was 50% (8/16 patients). The combination of ketamine and/or fentanyl transmucosal had an analgesic efficacy of 94.1% (15/16 patients). The adverse effects were associated with the ketamine mouthwash; all side effects were transient and subsided when the ketamine mouthwash was stopped. ConclusionKetamine mouthwash for orofacial pain due to cancer may be an effective treatment option. In cases of reported episodes of breakthrough pain, the combination of a ketamine mouthwash and oral transmucosal fentanyl citrate may be a viable treatment option in refractory mucositis pain.

Prehospital pain medication use by U.S. Forces in Afghanistan.

We report the results of a process improvement initiative to examine the current use and safety of prehospital pain medications by U.S. Forces in Afghanistan. Prehospital pain medication data were prospectively collected on 309 casualties evacuated from point of injury (POI) to surgical hospitals from October 2012 to March 2013. Vital signs obtained from POI and flight medics and on arrival to surgical hospitals were compared using one-way analysis of variance test. 119 casualties (39%) received pain medication during POI care and 283 (92%) received pain medication during tactical evacuation (TACEVAC). Morphine and oral transmucosal fentanyl citrate were the most commonly used pain medications during POI care, whereas ketamine and fentanyl predominated during TACEVAC. Ketamine was associated with increase in systolic blood pressure compared to morphine (+7 ± 17 versus -3 ± 14 mm Hg, p = 0.04). There was no difference in vital signs on arrival to the hospital between casualties who received no pain medication, morphine, fentanyl, or ketamine during TACEVAC. In this convenience sample, fentanyl and ketamine were as safe as morphine for prehospital use within the dose ranges administered. Future efforts to improve battlefield pain control should focus on improved delivery of pain control at POI and the role of combination therapies.