Fentanyl Transdermal System Research Articles

Efficacy of Fentanyl Transdermal Patch in Impacted Mandibular Third Molar Surgery-A Comparative Study.

Removal of mandibular third molars surgically is one of the most frequently performed oral surgical procedures which are often accompanied with post-operative pain, swelling and trismus. Despite general progress in pain management, moderate to severe acute post-operative pain after removal of lower third molars remains a problem. Fentanyl is an extremely effective drug in the treatment of severe chronic pain such as cancer pain and post-operative pains which acts by increasing patient's tolerance to pain. Fentanyl Transdermal System (FTS) is a rectangular transdermal patch which contains high concentration of fentanyl, a potent short-acting Schedule II opiate. In this study the efficacy of transdermal fentanyl for management of post-operative pain after impacted mandibular 3rd molar surgery is evaluated. 20 patients within the age group of 18-40 years with asymptomatic impacted mandibular third molars were equally divided into 2 groups as group A & group B which underwent surgery in Local Anaesthesia. In every patient one side belonged to group A and other side belonged to group B. 50 μg FTS was applied in group A while placebo patch was applied in group B. Patients in group A performed significantly better than group B in terms of mean pain intensity scores assessed by VAS and VRS along with minimum need of post-operative rescue analgesics. It was found that FTS resulted in significantly better pain relief, longer pain-free intervals, and lesser post-operative analgesic consumption.

Evaluation of in vitro/in vivo correlations for three fentanyl transdermal delivery systems using in vitro skin permeation testing and human pharmacokinetic studies under the influence of transient heat application

The value of developing an in vitro/in vivo correlation (IVIVC) is substantial in biopharmaceutical drug development because once the model is developed and validated, an in vitro method may be used to efficiently assess and predict drug product performance in vivo. In this study, three bioequivalent, matrix-type, fentanyl transdermal delivery systems (TDS) were evaluated in vitro using an in vitro permeation test (IVPT) and dermatomed human skin, and in vivo in human pharmacokinetic (PK) studies under harmonized study designs to evaluate IVIVC. The study designs included 1 h of transient heat application (42 ± 2°C) at either 11 h or 18 h after TDS application to concurrently investigate the influence of heat on drug bioavailability from TDS and the feasibility of IVPT to predict the effects of heat on TDS in vivo. Level A (point-to-point) and Level C (single point) IVIVCs were evaluated by using PK-based mathematical equations and building IVIVC models between in vitro fraction of drug permeation and in vivo fraction of drug absorption. The study results showed that the three differently formulated fentanyl TDS have comparable (p > 0.05) heat effects both in vitro and in vivo. In addition, the predicted steady-state concentration (Css) from in vitro flux data and the observed Css in vivo showed no significant differences (p > 0.05). However, the effects of heat on enhancement of fentanyl bioavailability observed in vivo were found to be greater compared to those observed in vitro for all three drug products, resulting in a weak prediction of the impact of heat on bioavailability from the in vitro data. The results from the current work suggest that while IVPT can be a useful tool to evaluate the performance of fentanyl TDS in vivo with a relatively good predictability at a normal temperature condition and to compare the effect of heat on drug delivery from differently formulated TDS, additional testing measures would enhance the ability to predict the heat effects in vivo with a lower prediction error.

Predicting Opioid Therapy Safety In Pancreatic Cancer Patients

Background — Obligatory use of strong opioids for treating chronic pain syndrome in patients with pancreatic cancer provides the implementation of opioid-associated adverse reactions. Genetic and non-genetic risk factors are predictive of the opioid therapy safety. Contemporary methods of information analysis allow using prognostic risk models for practical application. Objective — Identification of significant risk factors for the development of opioid-associated adverse drug reactions in patients with chronic pain syndrome against the background of pancreatic cancer. Material and Methods — The study included 90 patients with chronic pain against the background of pancreatic cancer, randomized at a ratio of 1: 1. Group 1 received morphine sulfate (MS), group 2 received fentanyl transdermal therapeutic system (FTTS) with standard adjuvant therapy (ketoprofen, diazepam, amitriptyline). To assess pain level, the 10-point Digital Rating Scale, the Visual Analogue Scale and the pain questionnaires were used. The assessment of the treatment safety was conducted by the Naranjo Scale. Assessment of prognostic genetic and non-genetic factors was carried out using ROC analysis with calculation of AUC (the area under the ROC-curve). Results — Prognostic models of good quality were determined with the optimal ratio of sensitivity and specificity for the influence of genetic and non-genetic risk factors on the development of opioid-associated adverse drug reactions (OA-ADRs) in comparison groups. Various prognostic factors, complementing each other, were identified in the comparison groups. Conclusion — The following OA-ADRs predicting factors were identified: for FTTS-associated nausea and vomiting – age and carriage of rs7438135 AG genotype of UGT2B7 gene; for local reactions – the sum of points on the ESAS scale and carriage of rs7438135 AA genotype of UGT2B7 gene; for difficulty urinating – the level of glomerular filtration rate; for neurotoxicity – the level of AST and bilirubin, and the carriage of rs1128503 GG genotype of ABCB1 gene; for pruritus – carriage of rs1045642642 AA genotype of ABCB1 gene. The prognostic factors for the implementation of MS-associated neurotoxicity were age and comorbidity; for dry mouth was predicted best from the sum of points on the MMCE scale; weakness was predicted by the carriage of rs7668258 TT genotype of UGT2B7 gene.

Method development and validation for the GC-FID assay of ethanol in reservoir-type fentanyl transdermal patches

With ethanol acting as a skin permeation enhancer in the reservoir-type fentanyl transdermal delivery system, accurate assay of ethanol in the adapted cosolvent system is an important quality control component. This paper describes the development and validation of an isothermal gas chromatography-flame ionization detection (GC-FID) method for the assay of ethanol in reservoir-type fentanyl patches (Durogesic(superscript ®). Samples were extracted with water by ultrasonic vibration using acetone as the internal standard. Using a polar column (Supelco OVI-G43, 30 m×0.53 mm) for the gas chromatographic analysis, ethanol and excipients were well resolved. The method was fully validated according to the ICH Q2A and Q2B guidelines. The range of linearity for ethanol was demonstrated from approximately 0.1 to 0.9 mg/mL (r^2＞0.99). The accuracy (recovery tests at 60, 100, and 140% of the nominal analytical concentration of 0.5 mg/mL) was determined in the range of 98~101% with RSD≤0.75%. The precision (repeatability or intermediate precision) was calculated as RSD≤1.21%. The detection and quantitation limits were determined to be 1.99 and 6.03 μg/mL, respectively. Furthermore, the robustness and system suitability testing were also considered. In conclusion, a validated method for the assay of ethanol in reservoir-type fentanyl transdermal patches was successfully applied to quality control practices.

Raman mapping of fentanyl transdermal delivery systems with off-label modifications.

Raman mapping is a powerful and emerging tool in characterization of pharmaceuticals and provides non-destructive chemical and structural identification with minimal sample preparation. One pharmaceutical form that is suitable but has not been studied in-depth with Raman mapping is transdermal delivery systems (TDS). TDS are dosage forms designed to deliver a therapeutically effective amount of active pharmaceutical ingredient (API) across a patient's skin. To enhance drug delivery through the skin, the API in the formulation is often close to a saturated or supersaturated state. Thus, improper use or off-label modifications can lead to occurrence of unwanted API changes, specifically, crystallization over time. Here, off-label modifications were mimicked on a set of fentanyl drug-in-adhesive TDS sold on the U.S. market by four different manufacturers via die cutting, and then the die cut TDS were investigated through confocal Raman mapping for structural and chemical changes. Using Multivariate Curve Resolution (MCR), not only was morphological and chemical characterization of transdermal systems provided, but also fentanyl crystals in certain products due to off-label modifications were identified. The chemometric model used in analysis of Raman maps allowed precise identification of fentanyl as the crystalline material as confirmed by the hit-quality-index correlation of component spectra from the chemometric model with library spectra of a fentanyl reference standard. The results show that confocal Raman mapping with MCR can be utilized in assessing pharmaceutical quality of TDS. This method has the potential to be widely used in characterization of such systems as an alternative to existing techniques.

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

Assessment of prior opioid tolerance among new users of fentanyl transdermal system in FDA's Sentinel System.

Fentanyl transdermal system (FTS) is intended only for patients with prior opioid tolerance. The purpose of this study is to identify the proportion of new FTS users who had evidence of prior opioid tolerance, by dosage strength, in FDA's Sentinel System. We identified new FTS episodes (183-day washout) from 2009 through 2013. Members were <65years and enrolled in medical and pharmacy coverage for 183days prior to initial FTS dispensing (index). We assessed the proportion of users with prior tolerance stratified by dosage strength of FTS using four definitions of opioid tolerance: ≥30-mg oxycodone equivalents/day in each of 7 consecutive days immediately prior to index; ≥30-mg oxycodone equivalents/day for any 7days in the 30days prior to index (secondary); any dose in each of 7days in the 7 consecutive days immediately prior to index (tertiary); and any dose for any 7days in the 30days prior to index (quaternary). Of 44450 episodes of 25 mcg/hr FTS, 37% met the primary definition, and 77% met the quaternary definition. Of 3507 episodes of 100 mcg/hr FTS, 57% and 74% met the primary and quaternary definitions, respectively. Those aged 25 to 34years had the highest proportion of episodes with prior tolerance; those aged 55 to 64 accounted for more of the episodes overall. In Sentinel, many new users of FTS did not have evidence of prior opioid tolerance by the primary definition, ie, the product label definition, which is the minimum standard for the lowest FTS dose (12 mcg/hr), especially at the highest strength (100 mcg/hr). Validation of this metric is warranted, but our findings suggest the need for further prescriber education regarding appropriate prescribing of FTS.

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.

Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system

Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States. An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 microg/h) and the matrix system (100 microg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours. Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application. The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast, and AUCinfinity) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments. The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.

Pain relief in pediatric palliative care: the place of fentanyl transdermal therapeutic system (according to the materials of Advisory Board Meeting)

Pain relief in pediatric palliative care: the place of fentanyl transdermal therapeutic system (according to the materials of Advisory Board Meeting)

The use of fentanyl in pain management in head and neck cancer patients: a narrative review.

Head and neck (H&N) cancers account for about 5% of all malignant tumours. Pain is one of the most feared consequences of H&N neoplasms and is experienced by up to 80% of patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing. Nevertheless, pain is still often underestimated and undertreated. The role of opioids in cancer pain has been well established but evidences about the role and the relative effectiveness of opioids such as fentanyl in the context of H&N cancer pain remains unclear. A literature review based on the guidance of the Centre for Reviews and Dissemination was conducted. An iterative approach was used starting with an electronic search in the MEDLINE database. The search terms (('Neoplasms'[Mesh]) AND 'Head and Neck Neoplasms'[Mesh]) AND 'Fentanyl'[Mesh] were used. A total of 18 publications were found by the first performed search on PubMed. Other publications concordant with our aim were found by cross-reference. Considering inclusion and exclusion criteria for our review, eight papers resulted eligible for analysis. Fentanyl transdermal therapeutic system (TTS) seems to be an important option, thanks to the way of administration, the good safety and tolerability profiles to control baseline pain. For breakthrough cancer pain (BTcP), several formulations of transmucosal fentanyl are available. All the formulations seem to be active and safety but we lack head-to-head studies of fentanyl versus other strong opioids, as well as with different formulation of fentanyl, particularly for BTcP where H&N cancer population is very poorly represented.

TRANSDERMAL FENTANYL: PHARMACOLOGICAL ASPECTS OF THERAPY IN CANCER PATIENTS. PART 1. FROM THE DEVELOPMENT OF TRANSDERMAL FENTANYL FORMULATIONS TILL META-ANALYSES OF CLINICAL TRIALS

There was given a review of data on pharmacology of fentanyl with focus on transdermal formulation. In the first part of the article improvements in technology of fentanyl transdermal patches were reviewed and advantages of the membrane-matrix system that are of practical use were highlighted. The results obtained from bioequivalence and therapeutic equivalence studies of traditional and improved transdermal fentanyl systems were given. Clinical trials with fentanyl transdermal patches as well as systematic reviews and meta-analyses on the efficacy and safety of transdermal fentanyl were summarized. The second part of the article will focus on factors contributing to the variability in pharmacokinetics and pharmacodynamics of fentanyl including pharmacogenetics; the taking into account the whole spectrum of these factors would allow to escaped the majority of errors during the administration of the drug e.g. transdermally. A special attention will be paid to basic principles and issues of the application of fentanyl transdermal therapeutic systems.

Alghedon Fentanyl Transdermal System.

The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain) is well established. Several formulations of fentanyl transdermal systems have been developed to improve the drug delivery and prevent misuse of the active principle. The addition of a rate controlling membrane to the matrix system represented an important advance. The design and functional features of Alghedon patch are compared with other approved generic fentanyl transdermal systems, emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid component in the finished product, therefore no leakage of active ingredient from the system can occur. A rate-controlling membrane provides controlled release of the active substance from the matrix reservoir, ensuring that fentanyl delivery and entry into the microcirculation is not solely controlled by the skin's permeability to this active substance. Alghedon patch contains part of the drug (approximately 15%) in the skin-contact adhesive: this innovative solution allows to overcome a typical drawback of transdermal patches, i.e. the long lag-time before the drug appears in plasma after the first administration, and provides rapid analgesia during the first hours of administration. Alghedon Fentanyl Transdermal System employs materials commonly used in other transdermal applications and having established safety profiles. For each strength level, the fentanyl content - and, thus, the resulting residual fentanyl remaining in the patch after use - is at the lowest end of the range used in commercially available fentanyl patches, minimizing the potential for abuse and misuse.

Efficacy of fentanyl transdermal patch in pain control after lower third molar surgery: A preliminary study.

BackgroundSurgical removal of impacted lower third molars is a common oral surgical procedure, generally followed by moderate to severe postoperative pain. Transdermal drug delivery as a concept offers interesting possibilities for postoperative pain control. The aim of this study was to evaluate the efficacy of transdermal system with fentanyl in relieving pain following impacted lower third molar surgery.Material and MethodsSeventeen patients with bilateral impacted lower third molars were included in this preliminary study. For postoperative pain control, patients randomly received a fentanyl patch plus placebo tablet after the first operation and regular (placebo) patch and an analgesic, after the second operation. Analgesia was evaluated during first 24 hours postoperatively according to patients’ reports about time of first pain appearance and additional analgesic consumption. Pain severity was rated using a 10 cm long visual analogue scale (VAS).ResultsIntensity of postoperative pain and postoperative analgesic consumption were significantly lower after the Fentanyl Transdermal System (FTS) was applied (p<0.05). Duration of postoperative analgesia was significantly higher with FTS when compared to control treatment (p<0.05).ConclusionsBased on the results of this preliminary study, transdermal system with fentanyl significantly reduced postoperative pain after third molar surgery. Key words:Analgesia, fentanyl, transdermal administration, third molar surgery, acute pain, postoperative care.

Long-term efficacy and safety of fentanyl transdermal system

Long-term efficacy and safety of fentanyl transdermal system

G303(P) Awareness of healthcare professionals about the possibility of substandard medicines

Aims The number of reports per year by the MHRA of substandard medicines is rising. The aim of this study was to examine healthcare professionals’ (HCPs) willingness to consider and report defective medicines. To gauge their awareness of reporting systems designed for HCPs to report defective medicines, issues related to medicine quality and the official online pharmacy logo (as the marker of legitimate online pharmacies). Methods This pilot study involved HCPs (paediatric doctors, pharmacists, and children’s nurses) and used self-administered questionnaires containing case scenarios derived from actual reported incidents. An invitation letter and questionnaire were sent to each doctor and nurse working at Derbyshire Children’s Hospital, as well as pharmacist members of the Nottinghamshire and Derbyshire Local Pharmacy Forum. Results 30 doctors (60% response rate), 31 pharmacists (2.7%), and 47 nurses (42%) responded, a total of 108 HCPs. Only 27 HCPs (23% doctors, 39% pharmacists, and 17% nurses) considered the possibility of manufacturer error when a medicine’s defect was obscure (fentanyl transdermal system with manufacturer error causing excessive release of the medicine). Most HCPs (77%, 74%, and 66%) responded that they would report such an incident via the Yellow Card Scheme, established to gather reports of adverse drug reactions. Most HCPs (100%, 87%, and 81%) agreed with the statement that ‘medicines in the UK are manufactured to a high standard’, though more than one-third (40%, 39%, and 30%) believed that poor-quality medicines existed in the medicine supply chain in the UK. However, only 5% of HCPs were aware of the defective medicines reporting system and few (7%, 16%, and 6%) were aware of the official online pharmacy logo. Conclusions HCPs’ awareness of the possibility of defective medicines was low. The vast majority were unaware of the defective medicines reporting system and of the official logo of registered online pharmacies in the UK. Findings suggest a need to increase HCPs’ awareness of these measures.

Inpatient prescribing and monitoring of fentanyl transdermal systems: adherence to safety regulations.

National safety guidelines were developed to minimize the occurrence of serious adverse drug events (ADEs) associated with the use of the fentanyl transdermal system (FTS), however, reports of use in opioid-naïve patients for treatment of acute pain and associated ADEs continue to occur. To evaluate the prescribing patterns of the FTS for adherence to recent US regulatory recommendations and identify the impact of health information technology (HIT) on adherence rates. A retrospective pre- and postintervention analysis was performed in hospitalized adult patients receiving FTS. Electronic medication order instructions and text questions were incorporated into FTS electronic medication orders. The primary outcome measure was adherence of FTS medication orders to regulatory guidelines defined as (a) a new order in an opioid-tolerant patient for use in moderate to severe chronic pain or (b) continuation of the documented home dose in use for at least 7 days. Safety measures included respiratory rate and documented ADEs. Adherence rates were significantly increased in the postintervention cohort as compared to the preintervention cohort (48.7% vs 85.0%; P < .0001). Incidence of ADEs was significantly lower post intervention (34.7% vs 23.3%; P = .043), including a lower incidence of respiratory depression (16.7% vs 8.3%; P = .043). Documentation was increased in the postintervention cohort (76% vs 100%). However, supporting documentation confirmed responses in only 59.2% of records reviewed. Incorporation of HIT via electronic order text questions increased overall adherence rates to regulatory recommendations, increased documentation, and decreased the rate of associated ADEs.

Implementation of an opioid management initiative by a state Medicaid program.

The utilization of prescription opioids has increased over the last 2 decades. Associated with this is the misuse of prescription opioids for nonmedical purposes. Medicaid programs have struggled with developing strategies that balance best practice models, appropriate utilization, and reduction in costs associated with the opioid medication class. To examine the impact of a 2-year stepwise initiative to reduce utilization and therapy costs of long-acting opioid analgesics (LAOA) by addressing issues of high dose, daily dose, and preferred therapeutic alternatives. Utilization data from the Massachusetts Medicaid pharmacy program for LAOAs were reviewed and compared for 2 time periods. The calendar year prior to the initiative, 2002, was used as a base year and represents a time period when there were no restrictions in place for members to obtain long-acting opioids. The calendar year 2005 was the comparison year representing a time period after the multiple steps of the initiative had been implemented. A retrospective claims-based analysis was performed to determine the impact of restrictions on LAOAs, defined as brand and generic versions of oxycodone ER, morphine ER, methadone, and fentanyl transdermal system. The primary measure was the percentage of change of unique utilizers, paid claims, and average daily dose for each LAOA following the implementation of the opioid management initiative. Secondary measures included a cost analysis. Compared with 2002, the overall number of LAOA unique utilizers declined 17.8% (P < 0.0001), and the overall number of claims declined by 4.1% (P < 0.0001), while Medicaid pharmacy benefit member enrollment remained relatively stable. Average daily dose declined in methadone and morphine ER and increased in oxycodone ER and fentanyl transdermal system. The 2005 overall cost of LAOAs decreased 8.0% compared with the overall cost in 2002. The per-member-per-month (PMPM) cost for opioid users in 2002 was $110.57 ($120.04 when adjusted to 2005 dollars) compared with $123.75 in 2005. In comparison, the overall PMPM for all members in 2002 was $3.52 ($3.82 when adjusted to 2005 dollars) compared with $3.59 in 2005. Our study successfully demonstrated that a state Medicaid program initiative can result in a significant overall decrease in opioid class utilization specifically for the targeted, more costly agents. This was achieved via the implementation of a Therapeutic Class Management multidisciplinary workgroup that established a prior authorization process implementing limits on dose, as well as identified preferred less costly agents. It further facilitated the direct opportunity for pharmacy-prescriber collaboration for LAOA medication management.

Conjugated Estrogens and Bazedoxifene

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The March 2014 monograph topics are umeclidinium and vilanterol inhalation powder, sucroferric oxyhydroxide, luliconazole, edoxaban, and secukinumab. The DUE/MUE is on fentanyl transdermal system.

The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p<0.05). The mean VASl and VASm scores measured on the 1(st), 2(nd), 3(rd), 4(th) and 5(th) days were found to be higher in Group IMO than in Groups IVPCA and TTS; however, these differences were not statistically significant (p>0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.