Fentanyl Patch in Reducing Intractable Pain in Patients with Amyotrophic Lateral Sclerosis: A Case Report

Abstract: We report a case of intractable pain in a patient with amyotrophic lateral sclerosis (ALS) that was successfully managed by administering a fentanyl transdermal patch. Case: A 75-year-old man was diagnosed with ALS in 2013 after he became aware of difficulty in walking and systemic pain since 2010. In 2019, he underwent gastrostomy and tracheostomy, and intractable generalized pain necessitated the administration of morphine hydrochloride six times a day; however, it could not provide adequate pain relief. Later, morphine was replaced with a fentanyl patch under a very strict safe-monitored setting and the pain became bearable. Discussion: Although high-level evidence is lacking, pain experts have reported the effectiveness of morphine for intractable pain in patients with ALS. Frequent short-acting morphine dosing is often burdensome due to the complexity of its administration and it also causes end-of-dose pain. A fentanyl patch may possibly improve these drawbacks.

The Efficacy of Fentanyl Transdermal Patch as the First-Line Medicine for the Conservative Treatment of Osteoporotic Compression Fracture / 대한신경손상학회지

OBJECTIVE: There are no strong guidelines on how long or how we should undertake conservative treatment during the acute period of an osteoporotic vertebral compression fracture (VCF). METHODS: We treated 202 patients with conservative treatment on VCF from March 2012 to August 2015. On inclusion criteria, 75 patients (22 males and 53 females) were included in the final analysis. After admission, a transdermal fentanyl patch with low dose (12.5 µg) application was attempted in all patients. In an unresponsive patient, the fentanyl patch was increased by 25 µg. After identifying the tolerable toilet ambulation of the patient without any assistance, hospital discharge was recommended. We classified two patient groups into one favorable group and one unfavorable group and compared several clinical and radiological factors. RESULTS: Among 75 patients, the clinical outcome of 57 patients (76%) was favorable, but that of 18 patients (24%) was unfavorable. In clinical outcomes, the numeric rating scale at 6 and 12 months and Odom's criteria at 12 months was significantly different between the favorable and the unfavorable groups. The dose of the patches used showed statistically significant differences between the two groups (p=0.001). CONCLUSION: The only statistically significant affecting factor for an unfavorable outcome was the use of a higher dose fentanyl patch. Our data inferred that the unresponsiveness to a low-dose fentanyl patch could be helpful to select patients necessary for percutaneous vertebroplasty or kyphoplasty.

A Case of Psychosis Following Delayed Encephalopathy of Transdermal Fentanyl Intoxication / 대한정신약물학회지

Fentanyl is a potent, synthetic opioid analgesic with a rapid onset and short duration of action. Recently, there have been many case reports that overuse or misuse of fentanyl patch resulted in fatal intoxication. Delayed hypoxic leukoencephalopathy typically manifests 2 to 40 days after apparent recovery from hypoxic event, and patients suffer from cognitive impairment, upper motor neuron signs, gait disturbance, or psychosis. We report first case of delayed encephalopathy with psychotic symptoms after overuse of fentanyl patch. Patient was found to have respiratory failure and mental change due to transdermal fentanyl overdose. She made a complete recovery in 2 weeks. After 4 weeks of the event, she readmitted with declining mental status. At 30 weeks after overdose, she complained of auditory and visual hallucination and showed paranoid delusion and odd behavior. Since admission into psychiatric unit, her psychotic symptoms have improved with antipsychotics. In conclusion, fentanyl patch should be used in order to prevent psychotic symptoms as well as medical complications.

Pigmentation by transdermal fentanyl patch

<b>Introduction</b>: There has been no case report in which hyperpigmentation developed on the skin area where a transdermal fentanyl patch was applied in a patient. <b>Case report</b>: A 43-year-old man with recurrence of postoperative rectal cancer was treated by cetuximab plus irinotecan and panitumumab plus FOLFIRI. For cancer pain, transdermal fentanyl patch (Fentos®) was administered, and radiation from behind was performed. Hyperpigmentation then appeared on the chest and the abdominal skin sites where the patches were applied. The hyperpigmentation nearly disappeared four months after the fentanyl patch was discontinued. <b>Discussion</b>: The cause of the pigmentation was possibly due to post inflammatory hyperpigmentation secondary to contact dermatitis. It was desirable to conduct patch test and skin biopsy for making an accurate diagnosis. <b>Conclusion</b>: We should pay a careful attention to hyperpigmentation of the skin where a transdermal fentanyl patch is applied.

Evaluation of the therapeutic efficacy of transdermal fentanyl patches in 39 patients with moderate to severe cancer pain / 中国药学杂志

OBJECTIVE: To evaluate the therapeutic efficacy of transdermal fentanyl patches for moderate to severe cancer pain in aspects of pain control, quality of life, ADR, and etc. METHODS: Using the standard case report form combined with brief pain inventory (BPI) and numerical rating scale (NRS), 39 patients with moderate to severe cancer pain who received transdermal fentanyl (initial dose of 25 μg · h-1) for no less than five weeks were investigated. RESULTS: The total effective rate was 97.4% (38/39) and the average pain relief degree was 60.3%. All the patients gained significant improvement in multiple aspects of the quality of life. The main ADRs included constipation, dizziness, nausea, drowsiness, skin itch and etc, which were endurable, especially in the later therapeutic period. CONCLUSION: Transdermal fentanyl patches are the ideal alternative for patients with moderate to severe cancer pain. Copyright 2012 by the Chinese Pharmaceutical Association.

Effect of nutritional status on transdermal fentanyl absorption in cancer patients

<b>Objective</b>: This study aimed to investigate the effect of nutritional status on estimated fentanyl absorption in cancer patients being treated with a fentanyl transdermal patch (FP), by measuring the residual fentanyl content in used patches. <b>Methods</b>: 24 adult Japanese inpatients receiving FP treatment for chronic cancer-related pain were enrolled. During FP application, the nutritional risk of the patients was measured using the Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening 2002 (NRS 2002), both of which are nutrition screening tools used widely in Japan. We then classified the patients into low-, medium-, and high-risk groups according to the nutritional risk measured by MUST, and compared the transdermal fentanyl delivery efficiency (FE) between that groups. <b>Results</b>: The FE, which is estimated by the residual fentanyl content in used FPs collected from the patients, was found to be decreased in the high-risk group. According to NRS 2002, the mean transdermal fentanyl delivery efficiency in the high-risk group was significantly lower than that in the low-risk group. <b>Conclusion</b>: These results showed that changes in nutritional status affect FE, and that poor nutritional status might decrease transdermal fentanyl absorption in cancer patients.

Dose conversion ratio for continuous intravenous infusion of fentanyl and fentanyl transdermal patches (reservoir-type)

Objectives: At present, the dose conversion ratio for a continuous intravenous infusion of fentanyl (CIV) and fentanyl transdermal patches (TP), which are widely used in Japan, is not based on the results of clinical studies in Japanese patients. Studies comparing serum fentanyl concentrations in patients with cancer pain treated by TP showed large differences between Japanese patients and those in other countries. We therefore studied the dose conversion ratio in Japanese patients. Methods: From October 2003 through October 2008, we extracted information on all patients with gastrointestinal cancer who underwent rotation from CIV to TP in the gastrointestinal ward of Kitasato University East Hospital. We selected patients in whom the daily dose of CIV or TP (i.e., the basic dose) was unchanged for 10 days after rotation and the difference in the number of rescue doses (per day) as compared with immediately before rotation was 1 or less on at least 3 consecutive days. All TP preparations used in this study were reservoir-type. Regression lines were plotted on the basis of the relation of “the basic released dose of TP” to “the basic prescribed dose of CIV,” and the dose conversion ratio was calculated. Results: 47 patients underwent opioid rotation, and 11 of them satisfied the eligibility criteria. Eleven patients were studied. The following regression equation was obtained: Y=1.0227X+1.0103, r²=0.9188, indicating a strong correlation. The dose conversion ratio of CIV to TP (released dose) derived by regression analysis was 1:1. Conclusions: Our results obtained in Japanese patients will allow dose conversion at the time of opioid rotation from CIV to TP to be more appropriately performed.

Effect of Transdermal Fentanyl Patches on the Motility of the Sphincter of Oddi

BACKGROUND/AIMS: Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. METHODS: SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5microgram/hr, respectively. RESULTS: Two of 16 patients receiving a 25microgram/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25microgram/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5microgram/hr TFP group (n=11 patients). CONCLUSIONS: TFPs below a dose of 25microgram/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO.

The effective rotation dose from fentanyl transdermal patch to other opioids

<b>Purpose</b>: A case of effective pain control by opioid rotation from fentanyl patch (oral morphine:fentanyl=100: 1 ratio) was succeeded with less than the theoretically equivalent conversion dose. Therefore, an investigation was undertaken to determine the effective rotation dose from fentanyl patch to other opioids. <b>Methods</b>: Retrospective analysis was carried out on patients with cancer-related pain, who were switched from fentanyl patch to other opioids. <b>Results</b>: Fourteen patients were analyzed and the average effective dose of opioids after the rotation was 76% of the theoretically calculated dose. Effective doses after opioid rotation were less than calculated doses in 11 cases (79%) and more than calculated doses in only 3 cases (21%). Effective doses after opioid rotation were 101% of calculated doses in cases (n=5) with less than 75μg/hr of fentanyl patch, but 63% in cases (n=9) with more than 75μg/hr. <b>Conclusion</b>: Opioid rotation should be considered when administration of more than 75μg/hr of fentanyl patch is needed. It is necessary to reduce the amount of applied dose to approximately 60% of calculated dose for safe opioid rotation. Moreover, it is necessary to remain careful and to provide immediate assistance in case of emergency due to withdrawal syndrome. Palliat Care Res 2009; 5(1): 301-307

A case of gastric cancer with abdominal pain in whom successful pain control was achieved by opioid rotation to morphine

<b>Introduction</b>: Although fentanyl patch (FP) are often used to treat cancer pain because of the low incidence of adverse effects of this formulation, there are cases in which it is impossible to eliminate the pain despite increasing the doses. We report a patient of advanced gastric cancer with abdominal pain, in whom successful pain control was achieved by opioid rotation from FP to continuous intravenous infusion of morphine hydrochloride. <b>Case Report</b>: The patient was a male in his 60's who had been diagnosed as having primary gastric cancer and complained of abdominal pain, thought to be visceral pain caused by obstruction of the digestive tract. Oral intake became more difficult as the disease progressed. Despite a switch to FP from oxycodone used to treat the abdominal pain and an increase in the dose, pain relief was not achieved. Then, we undertook a partial opioid rotation to continuous intravenous infusion of morphine hydrochloride, which provided adequate pain control. <b>Discussion</b>: One possible reason for the pain relief in this patient is suppression of the gastrointestinal motility by morphine. When adequate pain relief cannot be achieved with one opioid, opioid rotation should be considered. We concluded that the opioid rotation should, however, be performed in a stepwise manner. Palliat Care Res 2009; 4(1): 307-311

Efficacy and safety of fentanyl patch in cancer patients from the active treatment period to the terminal stage

A correction of a coauthor's name from Chigusa Nakamura to Chigusa Nakagawa on the author list and the abstract.

Efficacy and safety of fentanyl patch in cancer patients from the active treatment period to the terminal stage

<b>Purpose</b>: From shortly after the fentanyl patch became commercially available, we have been using it as part of our armamentarium for cancer therapy to produce a reliable analgesic effect from the active treatment period to the terminal stage in patients who are expected to develop resistance to oral analgesics. To confirm the usefulness of fentanyl patch, a retrospective study was conducted to determine its efficacy and safety. <b>Method</b>: A survey was conducted of 28 cancer patients who were undergoing pharmacological pain control. The following parameters were recorded: opioids administered prior to fentanyl patch use, reasons for switching to fentanyl patch, duration of administration and dosage of fentanyl patch, pain score before switching to fentanyl patch, adverse effects (nausea, vomiting, constipation and drowsiness), and the results of clinical tests. <b>Results</b>: The major reasons for switching to fentanyl patch were: "pain control with oral agents was expected to become difficult in future" and "adverse effects of chemotherapy were noted or were likely to develop". The mean duration of fentanyl patch use was 133 days, during which time the pain score and the constipation symptom were significantly reduced. No significant difference was found with nausea, vomiting, drowsiness or the results of clinical tests. <b>Conclusion</b>: It is concluded that fentanyl patch is a highly useful opioid for analgesia when administered during chemotherapy for cancer and continued to the terminal stage.

The Effect of Fentanyl Patch in the Treatment of Intractable Postherpetic Neuralgia / 대한피부과학회지

BACKGROUND: Postherpetic neuralgia is a persistant pain which occurs after the reactivation of varicella zoster infection. It sometimes disrupts the lives of otherwise healthy individuals. A transdermal patch of analgesics such as fentanyl could be a novel and safe method, with less adverse problems, to relieve the prolonged pain in postherpetic neuralgia. OBJECTIVE: The aim of this study was to evaluate the analgesic effect and safety of transdermal fentanyl patch in intractable postherpetic neuralgia. METHODS: We applied a fentanyl patch on the chest for 6 days, changing it once on the fourth day. The severity of pain was evaluated by visual analogue scale (VAS), and was assessed before treatment, the first and third day after commencement of treatment, and 1 day after treatment had finished. Any side effects were also checked at each VAS assessment session. RESULTS: The average VAS pain score of the pretreatment, first, third, and seventh day were as follows; 82.9+/-8.8, 49.6+/-15.8, 45.0+/-16.5, 45.7+/-15.2. Postherpetic neuralgia was dramatically improved from the first day of treatment, and the improved state was maintained until 1 day after the treatment had finished (p<0.05). Several side effects such as contact dermatitis (9.5%), mild nausea (14.3%), and constipation (9.5%) were observed during the treatment. CONCLUSION: Fentanyl patch is an effective, simple and relatively safe method in the treatment of intractable postherpetic neuralgia.

Successful Treatment with High Dose Transdermal Fentanyl Patch for Severe Cancer Pain in a Patient with Lung Cancer / 결핵및호흡기질환

A 60-year-old man was diagnosed with locally advanced non-small cell lung cancer. He refused treatment with a curative aim and was treated conservatively. Pain had developed on his shoulder and chest wall, which became worse as the cancer progressed. Although his pain initially appeared to be relieved with weak opioids and analgesics, it became more severe Strong opioids (transdermal fentanly patch and oxycodone), antidepressant or epidural block were introduced, However, the background pain became more intense and reached up to 8~9/10 on the visual analog scale (VAS). The dose of the transdermal fentanl patch was gradually increased to 600?g/hr, which resulted in a dramatic improvement in his pain (9/10 of VAS) to 3/10 for most of the time. We described the successful experience with a high dose transdermal fentanyl patch for cancer pain relief, which might be an alternative option for cancer patients suffering from severe pain.

A case of successful treatment with a combination of morphine and a fentanyl patch in a patient suffering from cancer pain accompanied by coughing and dyspnea

<b>Objective</b>: Opioid analgesics are normally administered as monotherapy. However, we experienced a patient in whom alleviations of cancer pain, coughing and dyspnea were successfully achieved with the combination therapy of morphine and a fentanyl patch (FP), and the case is reported herein. <b>Case Report</b>: A woman in her fifties, suffering from sigmoid colon cancer, liver and lung metastases, and associated pain complicated with coughing and dyspnea, manifested symptomatic alleviations following the facilitation of treatment with morphine sulphate. Taking into consideration that oral intake would become difficult at some time in the future, treatment switchover to FP was planned. However, in view of the efficacy of fentanyl against coughing and dyspnea having not yet been firmly established, a low dose of morphine sulphate for coughing and dyspnea continued and cancer pain was controlled with FP. Thus, through continued combined use of the two ingredients, morphine and fentanyl, until treatment end, symptomatic alleviations of pain, coughing and dyspnea were able to be achieved. <b>Conclusion</b>: For patients experiencing difficulty with oral intake and suffering from coughing and dyspnea in addition to cancer pain, combined use of a low dose of morphine and FP is considered useful in achieving a stable alleviation of such symptoms.