-
Journal of Pain and Symptom Management Oct 2013Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray.
OBJECTIVES
To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator.
METHODS
Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP.
RESULTS
Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability).
CONCLUSION
This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP.
Topics: Administration, Oral; Analgesics, Opioid; Breakthrough Pain; Causality; Comorbidity; Controlled Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Fentanyl; Humans; Male; Morphine; Neoplasms; Prevalence; Risk Factors; Treatment Outcome
PubMed: 23380337
DOI: 10.1016/j.jpainsymman.2012.09.009 -
MMWR. Morbidity and Mortality Weekly... Jan 2019Unintentional drug overdose deaths have climbed to record high levels, claiming approximately 70,000 lives in the United States in 2017 alone (1). The emergence of...
Unintentional drug overdose deaths have climbed to record high levels, claiming approximately 70,000 lives in the United States in 2017 alone (1). The emergence of illicitly manufactured fentanyl* (a synthetic, short-acting opioid with 50-100 times the potency of morphine) mixed into heroin, cocaine, and counterfeit pills, with or without the users' knowledge, has increased the risk for fatal overdose (2,3). The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducts routine overdose mortality surveillance by linking death certificates with toxicology findings from the NYC Office of the Chief Medical Examiner (OCME). A 55% increase in the rate of fatal drug overdose in NYC was observed from 2015 to 2017, resulting in the highest number of overdose deaths recorded since systematic reporting began in 2000. Toxicology data indicate that this unprecedented increase in overdose deaths is attributable to fentanyl. Early identification of increased fentanyl involvement enabled DOHMH to respond rapidly to the opioid overdose epidemic by increasing awareness of the risks associated with fentanyl and developing effective risk reduction messaging. These results strongly suggest that, wherever possible, jurisdictions should consider integrating toxicology findings into routine overdose surveillance and work with local medical examiners or coroners to include fentanyl in the literal text on death certificates.
Topics: Drug Overdose; Fentanyl; Humans; New York City
PubMed: 30653482
DOI: 10.15585/mmwr.mm6802a3 -
Scientific Reports Jul 2020The recent emergence of new fentanyl analogues and synthetic opioids on the drug market poses a global public health threat. However, these compounds cannot typically be...
The recent emergence of new fentanyl analogues and synthetic opioids on the drug market poses a global public health threat. However, these compounds cannot typically be identified using existing analytical methods. In this study, we aimed to develop and validate a rapid and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 37 fentanyl analogues and novel synthetic opioids in hair samples. Hair samples (20 mg) were extracted by cryogenic grinding in an extraction medium of methanol, acetonitrile, and 2 mmol/L ammonium acetate (pH 5.3). Following centrifugation of the samples, the analytes were separated using a WATERS Acquity UPLC HSS T column. The limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.5 to 2.5 pg/mg and from 2 to 5 pg/mg, respectively. The intraday and interday precisions were within 13.32% at LOQ, low, medium, and high levels. The accuracies were within the range of 85.63-116.1%. The extraction recoveries were in the range of 89.42-119.68%, and the matrix effects were within the range of 44.81-119.77%. Furthermore, the method was successfully applied to the detection and quantification of fentanyl and sufentanil in hair samples from two authentic cases. Thus, this method has great potential for detecting fentanyl analogues and novel synthetic opioids in forensic work.
Topics: Analgesics, Opioid; Chromatography, High Pressure Liquid; Fentanyl; Hair; Humans; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 32665579
DOI: 10.1038/s41598-020-68348-w -
Scandinavian Journal of Trauma,... Jan 2023Pain is one of the major prehospital symptoms in trauma patients and requires prompt management. Recent studies have reported insufficient analgesia after prehospital... (Observational Study)
Observational Study
BACKGROUND
Pain 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.
METHODS
This 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.
RESULTS
OTFC 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.
CONCLUSIONS
Prehospital 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.
Topics: Humans; Female; Male; Fentanyl; Analgesics, Opioid; Administration, Oral; Pain; Analgesia; Cohort Studies; Emergency Medical Services
PubMed: 36609399
DOI: 10.1186/s13049-023-01066-0 -
Medicine Jan 2022Patients with coronavirus disease (COVID-19) commonly experience distressing and challenging respiratory symptoms. Interventions such as oxygen therapy, oral opiates,...
Patients with coronavirus disease (COVID-19) commonly experience distressing and challenging respiratory symptoms. Interventions such as oxygen therapy, oral opiates, and traditional nebulizers like ipratropium bromide and salbutamol are variable in their efficacy, and therapy responses in patients are difficult to predict. The purpose of this study is to investigate the efficacy of nebulized fentanyl citrate on dyspnea, cough, and throat pain in patients with COVID-19 and evaluate the safety with any potential adverse events.In COVID-19, about 59% of patients will exhibit cough, 35% generalized body ache and sore throat, and 31% dyspnea. Some methods such as nebulized lidocaine, magnesium sulfate, and systemic opioids have been used to manage the respiratory symptoms. It has been previously shown that fentanyl nebulizer has beneficial effect in improving shortness of breath in patients with chronic obstructive pulmonary disease. The proposed theory behind that was that fentanyl decreased the rate of spontaneous respiratory rate, diminished the brain stem chemoreceptor response to hypoxia and hypercarbia, in addition to exhibiting a modulating effect on the brain stem. Therefore, we hypothesize that nebulized fentanyl has superior effect in improving shortness of breath and relieving cough compared to normal saline, in addition to its advantageous throat pain relief, while exhibiting fewer side effects in patients with COVID 19 infection. Therefore, this phase-III, randomized, comparative, parallel assignment, single-blinded clinical trial aims at assessing the efficacy and safety of nebulized fentanyl to suppress cough, improve breathlessness, and relieve throat pain in patients with COVID-19.
Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analgesics, Opioid; COVID-19; Clinical Trials, Phase III as Topic; Cough; Dyspnea; Fentanyl; Humans; Middle Aged; Nebulizers and Vaporizers; Pharyngitis; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult; COVID-19 Drug Treatment
PubMed: 35089202
DOI: 10.1097/MD.0000000000028637 -
Drug Design, Development and Therapy 2020The combination of naloxone hydrochloride (NH) and fentanyl citrate (FC) in patient-controlled analgesia (PCA) is examined to reduce the risk of opioid-induced nausea...
Physical Compatibility and Chemical Stability of Fentanyl and Naloxone Hydrochloride in 0.9% Sodium Chloride Injection Solution for Patient-Controlled Analgesia Administration.
BACKGROUND AND OBJECTIVE
The combination of naloxone hydrochloride (NH) and fentanyl citrate (FC) in patient-controlled analgesia (PCA) is examined to reduce the risk of opioid-induced nausea and vomiting. However, there are no such commercially available drug mixtures, and there is also no published evidence on the compatibility and stability of NH and FC. Thus, the primary purpose of the current research is to investigate the physical compatibility and chemical stability of NH when mixed with FC over a 72-h period in a 0.9% sodium chloride injection solution for PCA administration under storage at 4°C and 25°C.
METHODS
Test solutions of 20 μg/mL FC and 4 μg/mL NH were prepared and stored in polyvinyl chloride (PVC) bags or glass bottles with a 0.9% sodium chloride injection solution as the diluent. During the 72-h storage period at 4°C or 25°C without light protection, the concentrations of the test drugs were assayed via high-performance liquid chromatography (HPLC), and the physical compatibility was determined with the naked eye. Furthermore, pH measurement of each sample was also performed with a pH meter.
RESULTS
The percentages of the initial concentrations of FC and NH in the various solutions were maintained at a minimum of 98% over the 72-h study period. All of the mixtures remained clear and colourless throughout the observation period, and no precipitation or turbidity was observed in any of the batches.
CONCLUSION
The 20 μg/mL FC test solution was physically compatible and chemically stable with the 4 μg/mL NH test solution when stored at 4°C or 25°C in PVC bags or glass bottles containing the 0.9% sodium chloride injection solution.
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Chromatography, High Pressure Liquid; Drug Incompatibility; Drug Packaging; Drug Stability; Fentanyl; Injections, Intravenous; Naloxone; Narcotic Antagonists; Reference Standards; Reproducibility of Results; Saline Solution
PubMed: 33116406
DOI: 10.2147/DDDT.S248209 -
Brazilian Journal of Anesthesiology... 2020In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case... (Comparative Study)
Comparative Study
STUDY OBJECTIVE
In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use.
DESIGN
In vitro prospective study.
SETTING
University Clinical Microbiology Laboratory.
MEASUREMENTS
In our study, in vitro antimicrobial effect of 0.05 mg.mL fentanyl citrate, 5 mg.mL bupivacaine were tested against American Type Culture Collection (ATCC) 29213, ATCC 27853, ATCC 13883, ATCC 25922 and ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. ATCC 29213, ATCC 27853, ATCC 13883 and ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18−24 hours at 37 °C.
MAIN RESULTS
In terms of inhibition zone diameters, ATCC 29213, ATCC 27853, and ATCC10231 values obtained after 12 and 24 hours of incubation were significantly higher in Group F than Group B ( < 0.001). In terms of inhibition zone diameters, ATCC 25922, and ATCC 13883 values obtained after 12 and 24 hours of incubation were significantly higher in Group B than Group F ( < 0.001, E. coli 12ª hour = 0.005).
CONCLUSIONS
Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.
Topics: Anesthetics, Local; Anti-Infective Agents; Bupivacaine; Drug Synergism; Fentanyl; Hydrochloric Acid; Microbial Sensitivity Tests; Prospective Studies; Sodium Hydroxide
PubMed: 32819727
DOI: 10.1016/j.bjan.2020.04.010 -
Anesthesiology Aug 1991Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia.... (Clinical Trial)
Clinical Trial
Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Administration, Oral; Adult; Biological Availability; Fentanyl; Half-Life; Humans; Infusions, Intravenous; Intestinal Absorption; Male; Mouth Mucosa; Random Allocation
PubMed: 1859010
DOI: 10.1097/00000542-199108000-00009 -
Journal of Analytical Toxicology Jan 2021Fentanyl analogs constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their...
Fentanyl analogs constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism, and studies utilizing liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis of hepatocyte incubations and/or authentic urine samples do not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study, seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogs, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogs, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogs where nothing is known about the metabolism.
Topics: Analgesics, Opioid; Chromatography, Liquid; Fentanyl; Hepatocytes; Humans; Mass Spectrometry; Reference Standards; Substance Abuse Detection
PubMed: 32104892
DOI: 10.1093/jat/bkaa021 -
Revista Da Associacao Medica Brasileira... Nov 2017The authors performed an economic assessment of opioids currently being used for control of postoperative pain relating to the surgical treatment of cancer (fentanyl and... (Comparative Study)
Comparative Study Review
OBJECTIVE
The authors performed an economic assessment of opioids currently being used for control of postoperative pain relating to the surgical treatment of cancer (fentanyl and sufentanil) within the Brazilian Unified Health System (SUS, in the Portuguese acronym).
METHOD
The assessment was based on the perspective of the government, in order to collaborate with the promotion of effectiveness in public policies of health, and to optimize the allocation of public resources into health. A cost-effectiveness analysis was performed using data collected from the Brazilian Unified Health System and information from literature review, in order to build a decision tree on the alternatives for control of postoperative pain related to cancer treatment among adult patients. The outcomes considered were: effectiveness of postoperative analgesia and occurrence of nausea and vomit in the 48 hour period after surgery, and additional 24-hour cycles in patient follow-up. A univariate sensitivity analysis was conducted in order to verify robustness of the model estimated.
RESULTS
Literature review showed a limited number of studies directly comparing fentanyl and sufentanil for control of postoperative pain. The adoption of sufentanil (cost = U$ 25.72 / outcome = 1.6 VAS points) was dominant in relation to the use of fentanyl (cost = U$ 32.58 / outcome = 2.6 VAS points). The estimated model showed robustness in relation to changes in the parameters analyzed.
CONCLUSION
Sufentanil presented higher cost-effectiveness ratio in relation to fentanyl for control of postoperative pain in surgeries related to cancer treatment among adult patients in the Brazilian Unified Health System.
Topics: Adult; Analgesics, Opioid; Brazil; Cost-Benefit Analysis; Fentanyl; Humans; National Health Programs; Neoplasms; Pain Measurement; Pain, Postoperative; Sufentanil
PubMed: 29451660
DOI: 10.1590/1806-9282.63.11.962