Sublingual Fentanyl Research Articles

Effectiveness and Safety of Sublingual Fentanyl in the Treatment of Breakthrough Cancer Pain in Older Patients with Cancer: Results from a Retrospective Observational Study

The study assessed sublingual fentanyl citrate (SFC) effectiveness and safety for breakthrough cancer pain (BtCP) in older patients. A multicenter, retrospective, observational study was conducted in three subgroups of cancer patients aged over 65 years with BtCP. The reports were collected by 20 oncologists across 12 hospitals. The primary goal was to measure changes in BtCP intensity with SFC treatment over 30 days; secondary objectives included pain relief onset and adverse events. A total of 127 patients with long-term cancer (mean: 3.3 years) were recruited. All of them had BtCP, mostly of mixed origin (62.5%). A significantly lower dose was needed in the high-age group at the final visit compared to baseline (212.90 ± 200.45 mcg vs. 206 ± 167.08 mcg; p = 0.000). Pain intensities at the beginning of the flare and at 30 min after SFC administration were significantly lower when the last and first visits were compared (1.9 vs. 2.3, p = 0.000; and 6.2 vs. 6.8 p = 0.006, respectively). The onset of analgesia was significantly more rapid for half of the patients ≥75 years, compared with 65–69 and 70–74 age groups. SFC appears then to be effective, well-tolerated, and safe to treat BtCP in older cancer patients.

Opioid analgesics for nociceptive cancer pain: Acomprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Fentanyl in cancer pain management: avoiding hasty judgments and discerning its potential benefits.

Cancer pain is an important challenge in treatment and requires a rapid onset of action for its control. In particular, breakthrough cancer pain (BTcP) should be adequately controlled with a stable dose of a short-acting oral opioid. Fentanyl is a synthetic, highly selective opioid with many advantageous chemical properties, including high lipophilicity and distinct pharmacokinetic properties. It is recommended for pain management in a variety of settings, including acute pain, chronic pain and BTcP. To date, its variously designed formulations allow non-invasive administration; amongst others, sublingual fentanyl has proven useful in the management of BTcP and in improving the quality of life of patients with cancer. This review provides an update on the management of BTcP with fentanyl, with consideration of safety, as it remains an important tool in the treatment of cancer pain.

Sublingual fentanyl for refractory episodic acute dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD): A real-world study

BACKGROUND Dyspnea is an extremely prevalent and debilitating symptom in chronic obstructive pulmonary disease (COPD), affecting up to 74% of patients despite optimal medical therapy. Sublingual fentanyl citrate (SLF) has a fast onset of action and a short half-life, both interesting characteristics to treat acute breakthrough dyspnea without inducing metabolite accumulation. The Montreal Chest Institute (MCI) COPD specialty clinic has been using low-dose SLF for patients with advanced COPD experiencing significant episodic dyspnea despite high intensity inhaled therapy. We present here a retrospective chart review, the largest to date, to report on a “real life” experience. METHODS All included patients had a formal diagnosis of COPD and were seen in the MCI COPD specialty clinic between January 1, 2015 and January 1, 2021. All patients prescribed SLF, irrespective of the duration of use, were enrolled in this chart review. Extent of symptom relief, categorized into either major, intermediate or no improvements, and adverse effects were inferred from in-person or telephone follow-up appointment clinical notes. An exacerbation was defined as a self-reported acute increase in symptoms leading to oral corticosteroid use or hospitalization. Rates of exacerbation and hospitalization in the 12 months before SLF initiation and during SLF use were compared. RESULTS In total, 17 COPD patients were given SLF during the study period. The mean FEV1 was 0.51 L (21% predicted). All participants reported MRC5/5 dyspnea and were prescribed regular low-dose oral morphine for daily breathlessness prior to SLF initiation. Most patients used SLF for more than 6 months, and 76.5% of the study group found intermediate or major improvement in breathlessness episodes. There was no significant change in the rates of exacerbation and admission for acute respiratory failure while on SLF. CONCLUSION In this review, we report real-life, long-term data on severe COPD patients using self-controlled as-needed SLF, showing patient acceptability, an improvement in dyspnea, and limited side effects. Hence, this represents an important step toward the first effective alternative rescue medication for the relief of breakthrough dyspnea since short-acting inhalers. Further study using a randomized trial design is required to confirm the efficacy of this therapy.

PAIN MANAGEMENT IN LUNG CANCERS : EXPERIENCE OF THE MEDICAL ONCOLOGY DEPARTMENT OF HASSAN II HOSPIATL IN FEZ

Despite advances in drug therapy, pain management for patients with lung cancer remains complex. Lung cancer is known to be one of the most painful cancers. Objective: In this study we evaluate the management of pain in patients treated for lung cancer, all stages combined, in the oncology department of the Hassan II University Hospital of Fez. Mean : cross-sectional study of 71 patients collected over a period of one year using a questionnaire specifying the characteristics of the pain, its etiology, the stage of the disease, the analgesic treatments prescribed and the relief obtained by the treatment. Results: The mean age of the patients was 63.5 years with extremes ranging from 48 to 85 years. Male gender was predominant (68%), 67% of patients had metastatic cancer: 42% had bone metastases. Nociceptive pain was assessed by the visual analog scale (VAS) and neuropathic pain by the DN4 Questionnaire. Severe pain, characterized by a VAS score higher than 7, or of moderate intensity with impact on sleep and daily activity, was reported in 60.5% of our patients, mostly young subjects, all with advanced cancer. The pain was acute in 5% of cases, subacute in 32% of patients and chronic in 63% of cases. Neuropathic pain was found in 23% of patients. The pain was controlled by analgesics, level II, in association with an anti-inflammatory agent or antidepressants in 37.3%. 62.7% of patients required morphine. An average daily dose of 60mg of morphine was required to relieve pain, 15 patients reported paroxysmal pain attacks of strong intensity requiring the prescription of sublingual Fentanyl. The use of analgesic radiotherapy in combination with morphine was noted in 10 patients (9.8%). However, a small percentage (2.8%) of patients were resistant to the above-mentioned analgesics, requiring the use of non-drug techniques to relieve them. Conclusion: Our survey confirms the persistent problem of inadequate management of cancer pain. An interesting approach is to improve.

PP071 A prospective, single-arm, open, multi-center, observational study of sublingual fentanyl for breakthrough cancer pain: Efficacy, safety, and tolerability in Korean cancer patients

PP071 A prospective, single-arm, open, multi-center, observational study of sublingual fentanyl for breakthrough cancer pain: Efficacy, safety, and tolerability in Korean cancer patients

EE176 Cost-Utility Analysis of Fentanyl Sublingual Formulation in the Treatment of Breakthrough Pain in Adults With Cancer, Already on Opioid Maintenance Therapy for Chronic Cancer Pain in Italy

The aim of this analysis was to quantify the advantages and the cost-utility of fentanyl sublingual formulation in terms of pain intensity reduction for each episode of breakthrough cancer pain (BTCP) compared to morphine therapy in Italy.

Low-dose sublingual fentanyl improves quality of life in patients with breakthrough cancer pain in palliative care.

Aim: This subanalysis of the CAVIDIOPAL study evaluated the impact of individualized management of breakthrough cancer pain (BTcP) with fentanyl on the quality of life (QoL) of advanced cancer patients in Spanish palliative care units. Patients & methods: This was a prospective, observational, multicenter study. The European Organization for Research and Treatment of Cancer's QLQ-C30 questionnaire was used at baseline (V0) and visit 28 (V28). Results: Ninety-five patients were mainly treated with 67-133μg fentanyl, showing a notable reduction in intensity (visual analog scale: 8.0 [V0] to 4.6 [V28]), frequency and duration of BTcPepisodes shortly after the first 1-2weeks of treatment, with significantly improved QoL (global health status: 31.1 [V0] to 53.1 [V28]). Conclusion: Low-dose sublingual fentanyl effectively reduced BTcPin advanced cancer patients in palliative care units, significantly improving QoL. Clinical trial registration: NCT02840500 (ClinicalTrials.gov).

Effectiveness of Sublingual Buprenorphine and Fentanyl Pump in Controlling Pain After Open Cholecystectomy.

BackgroundThe proper management of postoperative pain improves patients’ quality of life, accelerates early postoperative recovery, shortens hospitalization period, and reduces medical costs. This study aimed to compare the effectiveness of intravenous fentanyl pump and sublingual buprenorphine tablet in controlling pain after open cholecystectomy.ObjectivesEvaluating the effectiveness of sublingual buprenorphine in reducing postoperative pain and complications after open cholecystectomy.MethodsThis study was a double-blind, randomized clinical trial. The study population encompassed those candidates undergoing open cholecystectomy, patients with ASA class I and II, individuals undergoing no other concomitant surgery, and patients in the age range of 20 - 50 years. The first group received sublingual buprenorphine 6, 12, and 18 hours after the first administration. The second group received fentanyl as patient-controlled analgesia (PCA) for 24 hours. Then nausea, vomiting, sedation, and Visual Analog Scale (VAS) scores were evaluated at the beginning, 2, 6, 12, 18, and 24 hours after surgery. The collected data were analyzed using SPSS software version 20.ResultsThe mean age of the patients in the buprenorphine and fentanyl groups were 44.8 ± 5.5 and 42.8 ± 7.1 years, respectively. In this study, 22.5% of the patients in the buprenorphine group and 35.5% of the patients in the fentanyl group were male. During 6 and 24 hours after surgery, the pain level regarding the VAS scores was significantly lower in the buprenorphine group than in the fentanyl group; however, analgesic consumption was higher in the fentanyl group. In the early hours after surgery (2 and 6 hours), nausea and vomiting were lower in the buprenorphine group than in the fentanyl group even though the difference was not significant.ConclusionsThis study suggests buprenorphine as an effective drug for patients to reduce postoperative pain because of its limited complications, inexpensiveness, and more convenient administration method.

A non-injected opioid analgesia protocol for acute pain crisis in adolescents and adults with sickle cell disease.

Initial management of the acute pain crisis (APC) of sickle cell disease (SCD) is often unsatisfactory, and might be improved by developing a standardised analgesia protocol. Here, we report the first stages in developing a standard oral protocol for adolescents and adults. Initially, we performed a dose finding study to determine the maximal tolerated dose of sublingual fentanyl (MTD SLF) given on arrival in the acute care facility, when combined with repeated doses of oral oxycodone. We used a dose escalation algorithm with two dosing ranges based on patient’s weight (<50 kg or >50 kg). We also made a preliminary evaluation of the safety and efficacy of the protocol. The study took place in a large tertiary centre in London, UK. Ninety patients in the age range 14–60 years were pre-consented and 31 treatment episodes were evaluated. The first 21 episodes constituted the dose escalation study, establishing the MTD SLF at 600 mcg (>50 kg) or 400 mcg (<50 kg). Further evaluation of the protocol indicated no evidence of severe opioid toxicity, nor increased incidence of acute chest syndrome (ACS). Between 0 and 6 hours, the overall gradient of reduction of visual analogue pain score (visual analogue scale (VAS)) was 0.32 centimetres (cm) per hour (95% confidence interval (CI) = 0.20 to 0.44, p < 0.001). For episodes on MTD SLF, there was median (interquartile range (IQR)) reduction in VAS score of 2.8 cm (0–4.2) and 59% had at least a 2.6-cm reduction. These results are supportive of further evaluation of this protocol for acute analgesia of APC in a hospital setting and potentially for supervised home management.

Risk indicators in tapentadol use: opportunities to improve outcomes with a personal pharmaceutical care approach in community pharmacies

Opioids have historically been the pharmacological choice in the treatment of moderate to severe pain of oncological and chronic origin but they have also become a growing and controversial tool in the treatment of non-oncological pain that requires a risk/ benefit evaluation. The present study focuses on the opioid tapentadol, the newest opioid considered highly effective in treating cancer and non-cancer pain. According to the WHO Collaborating Center for Drugs Statistics Methodology, the stated Tapendatol Defined Daily Dose (DDD) for oral administration is 400 mg but the prescribed doses range from 100 mg/day in patients without previous opioid treatments up to a maximum of 600 mg/ day. However, the DDD is a unit of measurement that does not have to reflect the prescribed daily dose (PDD) because therapeutic doses usually differ from DDDs by taking into account individual patient considerations and pharmacokinetic conditions. This retrospective observational study in a community pharmacy on the island of Tenerife (Canary Islands, Spain) is based on the 471 dispensations of opioids for the year 2020, of which 213 correspond to tapentadol (45.2%). In 2020, among the 62 patients using opioids, 58% (36) were treated with tapentadol. For both genders, the predominant age range among tapentadol users is over 61 years, accounting for 70% of the sample (50% women and 20% men). Regarding the origin of the prescription of tapentadol, 68% of the prescriptions were originated in Primary Care services and only 14% were prescribed at a Hospital. Recorded tapentadol PDDs range from 25 mg/day to 500 mg/day but the most prescribed PDD in both women (22%) and men (11%) was 100 mg/day. When studying the polymedication of tapentadol users we observed that 36% of them are also treated with benzodiazepines (34% women and 2% men), 34% also use SSRI antidepressants (32% women and 2% men), 15 % take antiepileptic drugs (13% women and 2% men) and 8% receive TCA antidepressants. The tapentadol dispensing was also recorded in synergy with other major opioids. Thus, 3.2% of patients (women over 61 years of age) receive a combination of oral tapentadol (150 mg and 200 mg) and oral sublingual fentanyl (0.13 mg - 0.4 mg/day). Therefore, the authors believe that in any pharmaceutical care intervention on opioids treatment users, especially dispensing and follow up, is an ideal time to promote a safer user of Tapentadol and to detect and to avoid potential drug related problems (DRP) and negative medicine outcomes (NMO).

Observational study of efficacy, safety, and tolerability of fentanyl in Korean cancer patients (OASIS)

Abstract Background: Sublingual fentanyl (Abstral) has been developed to provide rapid-onset analgesia in breakthrough cancer pain (BTcP). While the efficacy and safety of the fentanyl tablet have been already confirmed in clinical trials, there is no real-world evidence regarding the effectiveness and safety of this agent in the control of BTcP. Aims: To observe the effectiveness, safety and tolerability of Abstral for the alleviation of BTcP in Korean patients. Methods: The study is a non-interventional, observational study conducted in 13 hospitals in the Republic of Korea. Cancer patients (targeted number: 309), prescribed with Abstral due to the inability to control BTcP with other fentanyl products, are to be followed up for 12 weeks to collect the information about dose titration, pain status, quality of life, and adverse events. Conclusions: The list of inclusion and exclusion criteria is relatively short, which will likely make the study group more representative for the entire population of cancer patients with BTcP. All treatment-related decisions are left solely on the investigator's discretion, which will enable to analyze the treatment outcomes in various clinical scenarios, unlikely to be tested in a traditional clinical trial. These two features seem to be essential for the successful management of BTcP, a highly heterogeneous condition requiring an individualized approach. Further, the study includes patients who did not respond to other fentanyl formulations, and hence, it might explain whether switching from one immediate-release fentanyl to another is associated with a clinical benefit and/or specific risk. Trial registration: ClinicalTrials.gov with the identifier NCT03895762.

Efficacy, safety, and tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study

Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients.The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8).A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey).Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.

Feasibility of a transmucosal sublingual fentanyl tablet as a procedural pain treatment in colonoscopy patients: a prospective placebo-controlled randomized study

Since patients often experience pain and unpleasantness during a colonoscopy, the present study aimed to evaluate the efficacy and safety of sublingually administered fentanyl tablets for pain treatment. Furthermore, since the use of intravenous drugs significantly increases colonoscopy costs, sublingual tablets could be a cost-effective alternative to intravenous sedation. We conducted a prospective placebo-controlled randomized study of 158 patients to evaluate the analgesic effect of a 100 µg dose of sublingual fentanyl administered before a colonoscopy. Pain, sedation, nausea, and satisfaction were assessed during the colonoscopy by the patients as well as the endoscopists and nurses. Respiratory rate and peripheral arteriolar oxygen saturation were monitored throughout the procedure. There were no differences between the fentanyl and placebo groups in any of the measured variables. The median pain intensity values, as measured using a numerical rating scale, were 4.5 in the fentanyl group and 5 in the placebo group. The sedation and oxygen saturation levels and the respiratory rate did not differ between the groups. The majority of the colonoscopies were completed.Our results indicate that a 100 µg dose of sublingual fentanyl is not beneficial compared to the placebo in the treatment of procedural pain during a colonoscopy.

Off-Label and Unlicensed Drugs in Pediatric Palliative Care: A Prospective Observational Study

ContextOff-label and unlicensed use of drugs is a widespread practice in pediatric care because of the lack of specific efficacy and safety data and the absence of formulations adapted to the needs of these individuals. Pediatric patients with a life-limiting illness frequently receive drugs under these conditions, although no studies have established the prevalence of this practice. ObjectivesTo describe the prevalence, indications, and most common uses of off-label and unlicensed drugs in a pediatric palliative care unit (PPCU). MethodsA prospective cross-sectional observational study carried out between January and October 2019. ResultsAbout 85 patients involving 1198 prescriptions were analyzed. A total of 39.6% were off label, and 12.9% were unlicensed. All received at least one off-label drug, with a median of five per patient (interquartile range 3–7), and 81.2% received at least one unlicensed drug. A total of 36.1% of the prescriptions were considered off label because of indication, 33.8% because of dosage, and 26.6% because of age. The main drugs used off label were oral morphine, oral levetiracetam, inhaled albuterol, sublingual ondansetron, oral tizanidine, sublingual fentanyl, and oral diazepam. The main symptoms treated with off-label drugs were dyspnea, pain, and nausea/vomiting. ConclusionMore than half of the prescriptions in this PPCU were off label or unlicensed. Treatment indication was one of the main reasons for off-label use. Administration of compounded preparations was common in patients with a life-limiting illness.

Fentanyl Sublingual Spray or Morphine for the Control of Shortness of Breath During or After Physical Activity in Cancer Patients

Fentanyl Sublingual Spray or Morphine for the Control of Shortness of Breath During or After Physical Activity in Cancer Patients

Sublingual Sufentanil vs Intravenous Fentanyl for Acute Pain in the Ambulatory Surgery Center

Sublingual Sufentanil vs Intravenous Fentanyl for Acute Pain in the Ambulatory Surgery Center

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial

ContextThe optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. ObjectivesWe examined the effect of two doses of prophylactic FSS on exertional dyspnea. MethodsIn this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%–45% (high dose) or 15%–25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0–10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. ResultsThirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change −1.42; 95% CI −2.37, −0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change −0.47; 95% CI −1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. ConclusionProphylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.

Effect of Sublingual Fentanyl on Breathlessness in COPD

Effect of Sublingual Fentanyl on Breathlessness in COPD

Effect of Opioid Exposure on Efficacy and Tolerability of Sublingual Fentanyl and Subcutaneous Morphine for Severe Cancer Pain Episodes. Secondary Analysis From a Double-Blind Double-Dummy, Randomized Trial

ContextFew studies have addressed the impact of previous opioid exposure on the effect of opioids for the treatment of severe cancer pain episodes. ObjectivesWe aimed to test whether previous exposure to higher opioid doses was associated with a reduced analgesic effect of fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) and whether it had an influence on their relative effect. MethodsThis is a secondary analysis of a placebo-controlled randomized trial comparing 100 μg FST with 5 mg SCM for the acute treatment of severe cancer pain episodes. The effect of previous opioid exposure (oral morphine equivalent daily dose from 20 to 120 mg) on pain intensity difference (PID) and side effects at 30 and 60 minutes after administration (PID 0–30 minutes, PID 0–60 minutes, and adverse events 30–60 minutes) and on re-medication for inefficacy, was studied by multivariable linear and logistic regression models and statistical tests for interaction. ResultsA total of 114 patients were enrolled. Results indicate modest and nonstatistically significant effect of previous opioid exposure on all the outcomes examined (P = 0.11, P = 0.35, P = 0.07, and P = 0.52, respectively, for PID 0–30 minutes, re-medication, PID 0–60 minutes, and adverse events 30–60 minutes). Nonstatistically significant tests for interaction for all models indicated a lack of impact of previous opioid exposure on the difference in the analgesic effect between treatments. ConclusionIn this study, we could not demonstrate an effect of previous opioid exposure, from 20 to 120 mg oral morphine equivalent daily dose, on the absolute and relative efficacy and tolerability of 100 μg FST and 5 mg SCM for severe cancer pain episodes.