• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.81-87
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• 2018

Objective: There have been many cases of spontaneous adverse drug reactions to fentanyl at a regional pharmacovigilance center in the hospital. To assess the factors causing the adverse drug reactions reported in patients receiving fentanyl patient-controlled analgesia (PCA) monotherapy or in combination with fentanyl transdermal therapeutic system (TTS) for acute post-operative pain management. Methods: We conducted a retrospective cohort study with all patients prescribed fentanyl PCA for pain management after orthopedic surgery at a single university hospital from June 2012 to May 2013. We analysed the factors causing adverse drug reactions reported by a spontaneous reporting system in patients receiving fentanyl PCA monotherapy and those receiving fentanyl TTS in combination with fentanyl PCA. Results: Based on the spontaneous adverse drug reaction reporting, the risk ratio for the incidence rate of adverse drug reaction in the fentanyl TTS combination therapy group was 3.04 (95 % CI: 2.4-4.00, P < 0.0001), which was approximately 3-fold higher than that reported for fentanyl PCA monotherapy. Only 60 % of the adverse drug reactions were reported. Conclusion: It is inappropriate to add fentanyl TTS to fentanyl PCA to manage post-operative acute pain. There is a need to improve adverse drug reaction reporting. We expect that regular analysis of adverse drug reactions reported at regional pharmacovigilance centre would aid in appropriate drug utilization by patients.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.223-228
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• 2008

The purpose of this study was to investigate the feasibility of developing transdermal drug delivery system (TDDS) for fentanyl used for the management of chronic cancer pain. The effect of type of pressure sensitive adhesive on the permeation of fentanyl from polyisobutylene (PIB), silicone and acrylic adhesive was evaluated. Due to the good adhesive force and relatively steady flux for 3 days, both acrylic and PIB adhesives were chosen for further study. The permeation rate of fentanyl was the highest from acrylic adhesive with hydroxyl functional group. Permeation rate increased linearly as the concentration of fentanyl in acrylic adhesive was increased from 2.5% to 10%. In case of PIB adhesive, crystals of fentanyl were developed above 5% drug load. $Crovol^{(R)}$ A40, $Crovol^{(R)}$ PK40 and Plurol $oleique^{(R)}$ provided higher flux of fentanyl.

• Journal of The Korean Society of Clinical Toxicology
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• v.11 no.1
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• pp.49-52
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• 2013

Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.171-175
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• 2001

Background: This purpose of this study is to compare the analgesic efficacy, occurrence of motor block and other side effects of 48 hr continuous postoperative epidural infusions with 0.125% ropivacaine with fentanyl or 0.15% ropivacaine with fentanyl. Methods: Forty patients undergoing Cesarean section were randomly allocated into two groups. Both groups received epidural injection of 2.0% lidocaine 19 ml and 0.75% ropivacaine 2-5 ml with fentanyl $50{\mu}g$ for 20 minutes before surgery. Following surgery, a continuous epidural infusion using a two- day infusor was given for 40 minutes for post-operative pain control. Group 1 (n = 20) then received 0.125% ropivacaine and 6 ug/ml of fentanyl at a rate of 2 ml/h. Group 2 (n = 20) received 0.15% ropivacaine and 6 ug/ml of fentanyl at the same rate. Visual analog scales (VAS) for pain during rest and movement, sensory change and motor blockade were assessed for 48 hr after surgery. Results: There were no significant differences in VAS for pain during rest or movement. The incidence of side effects was similar in both groups. Conclusions: Using 0.125% ropivacaine with fentanyl via an epidural route provided similar pain relief and side effects as 0.15% ropivacaine with fentanyl.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.67-73
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• 2000

Background: This study intends to evaluate the benefits of the administation of continuous infusion and demand doses of 0.125% ropivacaine compared with 0.125% bupivacaine after addition of fentanyl using patient controlled epidural analgesia (PCEA) for pain control during labor. Methods: Thirty-nine American Society of Anesthesiologists physical status 1 or 2 parturients were randomized by double blind design to receive either 0.125% bupivacaine with fentanyl 1 ug/ml or equivalent concentration of ropivacaine/fentanyl using PCEA; with 6~8 ml/hr basal rate, 3 ml bolus, 5 min lockout, 30 ml/hr dose limit. We assessed analgesia, the amount of study solution used in PCEA, sensory levels, motor block (0~3 scales), side effects and patient satisfaction. A postpartum questionnaire was carried out afterward. Results: There were no differences in visual analogue scores (VAS) for pain, hourly study solution use, sensory levels, side effects and patient satisfaction between groups. However, patients administered ropivacaine/fentanyl had significantly less demand, less administered in PCEA, less numbness and restriction of movement compared with patients in the bupivacaine/fentanyl group. Conclusions: Ropivacaine 0.125% with fentanyl, when administerd epidurally by PCEA for labor analgesia, was equally efficious as bupivaciane 0.125% with fentanyl, having with minimal numbness and restriction of motion.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.17-23
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• 2018

Objective: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. Methods: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. Results: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. Conclusion: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.117-128
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• 2022

Background: Moderate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times. Methods: In this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups. Results: Eighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO₂ was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO₂ levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05). Conclusion: The combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.417-422
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• 2013

The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 ${\mu}g/kg$. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneously) to Group 5, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 ${\mu}g/kg$ dexmedetomidine (subcutaneous)+5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.10015-10020
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• 2014

Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and Methods: The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-${\kappa}B$ were evaluated by Western blotting and the levels of Sirt1 and NF-${\kappa}B$ by fluorescence method. SiRNA was used to silence and Ad-Sirt1 to overexpress Sirt1. Results: Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover, fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-${\kappa}B$, which might be mechanisms of fentanyl action. Conclusions: Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-${\kappa}B$ activation in a Sirt1-dependent manner.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.181-186
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• 2005

Background: Hydromorphone has an intermediate lipid solubility range that falls between morphine and fentanyl. Lipophilic activity during opioid epidural administration is important in relation to both the side effects and analgesic efficacy. The purpose of this study was to compare epidural hydromorphone and fentanyl when concomitantly infused with bupivacaine in patients undergoing a thoracotomy. Methods: Seventy-seven thoracotomy patients, with patient-controlled epidural analgesia (PCEA), were blindly allocated into two groups [group F (n = 34); 0.1% bupivacaine and fentanyl $5{\mu}g/ml$, group H (n = 34); 0.1% bupivacaine and hydromorphone $16{\mu}g/ml$)]. The basal PCEA rate and demand dose were 4 ml/hr and 3 ml, respectively. The visual analogue scale (VAS) for pain, and pruritus, sedation and nausea were measured at 6, 12 and 24 hours after the operation. Results: There were no significant differences in the VAS pain scores and the incidences of pruritus, nausea and sedation between the two groups. The total infused volume after 24 hours was lower in H compared to that of F group (P < 0.05). Conclusions: We conclude that epidural hydromorphone or fentanyl administration has a similar analgesic efficacy and shows similar incidences of side effects, when concomitantly infused with bupivacaine, in the management of acute pain following a thoracotomy.