Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized,double-blind,placebo-controlled study

Abstract

Background and objectives:

A number of transmucosal fentanyl formulations have been developed for the management of breakthrough cancer pain (BTCP). Sublingual delivery of fentanyl, formulated as fentanyl sublingual spray, offers the potential for more rapid and greater absorption of fentanyl and associated onset of analgesic effect compared with other formulations. The objective of this study was to assess the efficacy and safety of fentanyl sublingual spray for the treatment of BTCP.     

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

BackgroundBreakthrough 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.ObjectiveThe purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.MethodThis 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).ResultsA 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).ConclusionSublingual 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.     

Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized,placebo-controlled study

ABSTRACT

Background: Short-acting opioids are commonly used to treat breakthrough pain (BTP) and rapid-onset formulations are being developed to improve the effectiveness of this approach. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia. FBT was evaluated for BTP in opioid-treated patients with chronic low back pain – the first such study in a population with chronic non-cancer pain.

Design: Randomized, double-blind, placebo-controlled.

Patients and setting: Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States.

Procedures: Following open-label titration to identify an effective FBT dose, patients were randomly assigned to one of three double-blind dose sequences (six doses of FBT, three placebo) to treat nine BTP episodes. Pain intensity (PI), measured on an 11-point scale (0 = no pain; 10 = worst pain), and other outcomes were assessed for 2?h after dosing.

Data analysis: The primary efficacy measure was the sum of pain intensity differences (PIDs) for the first 60?min (SPID₆₀); secondary efficacy measures included PIDs at other time points, pain relief (PR), meaningful PR, time to meaningful PR, use of supplementary BTP medication, and self/investigator-reported adverse events.

Results: Of the 124 patients screened, 105 patients were enrolled, 84 identified an effective FBT dose, and 77 entered the double-blind phase. SPID₆₀ significantly favored FBT (?p < 0.0001). All secondary measures also favored FBT, with PIDs and PR showing significant differences versus placebo as early as 10 and 15?min, respectively. An improvement in PI score of ≥ 33% occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15?min (20% vs. 11%, p < 0.01) through 2?h (65% vs. 28%, p < 0.0001). Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT. AEs were typical for opioids, and were mostly reported during dose titration. Limitations of this study may be related to its open-label dose-titration phase (which has the potential to compromise blinding) and the recruitment of patients from pain clinics, which could potentially yield a study population that is not representative of the general population with BTP.

Conclusions: FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain.     

Tapentadol in cancer pain management: a prospective open-label study

Abstract

Objectives:

The aim of this prospective, open-label study was to evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain.     

Prospects and challenges in opioid analgesia for pain management

Abstract

Pain is still one of the most prevalent and distressing symptom in patients with chronic pain. Opioids are the most potent existing analgesics available in clinical practice. However, they are not always effective, particularly in the non-cancer population. Alternately adverse effects may limit their analgesic activity. Several different drug-development strategies have attempted to reduce side effects by exploiting anatomic barriers to drug distribution and to provide different analgesic mechanisms, as in the case of the oxycodone–naloxone combination or tapentadol. New delivery systems have been developed for a more effective management of breakthrough pain. Pharmacogenetics could play a critical role in personalizing pain management in the future.     

Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses

Abstract

Objectives:

The aim of this study was to compare the efficacy and safety of doses of fentanyl buccal tablet (FBT) proportional to doses of opioids used for background analgesia versus dose titration starting with the minimal dose for the management of breakthrough cancer pain (BTcP).     

Long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet for the treatment of breakthrough cancer pain

Abstract

Background and objectives:

Breakthrough cancer pain (BTcP) is a transient exacerbation of cancer pain in patients with otherwise stable, persistent background pain. This study evaluated the long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in opioid-tolerant patients with cancer.     

经鼻点滴枸橼酸芬太尼注射液用于控制爆发性癌痛的临床观察

目的探讨经鼻点滴枸橼酸芬太尼注射液用于控制爆发性癌痛(BTCP)的有效性。方法 18例晚期癌症且合并BTCP住院患者,均口服吗啡缓释片控制基础性癌痛,口服吗啡即释剂控制BTCP。随机分为两组(n=9):观察组在BTCP时改用枸橼酸芬太尼注射液1ml(50μg)滴鼻。对照组:继续用吗啡即释剂控制BTCP。结果观察组与对照组镇痛起效时间分别为(18.34±6.33)和(25.11±4.26)min,观察组显著短于对照(P<0.05)。观察组BTCP最大强度评分显著低于对照组(P<0.05),而患者满意度评分显著高于对照组(P<0.01)。结论枸橼酸芬太尼注射液滴鼻用于控制BTCP,给药方便,起效迅速,患者满意度高,有一定的临床应用价值。     

The use of sublingual fentanyl for breakthrough pain by using doses proportional to opioid basal regimen

Abstract

Objective:

The aim of this study was to prospectively assess the efficacy and safety of sublingual fentanyl (SLF) in doses proportional to opioid doses used for background analgesia for the treatment of BTP of cancer patients.     

Sublingual fentanyl orally disintegrating tablet in daily practice: efficacy,safety and tolerability in patients with breakthrough cancer pain

Abstract

Background and objectives:

Breakthrough cancer pain (BTcP) affects more than half of patients with cancer pain and has severe detrimental impacts on quality of life (QoL). This study evaluated the efficacy, QoL impact and safety of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in a clinical setting.     

Treatment of breakthrough cancer pain: to titrate or to proportionate?

Abstract

Breakthrough cancer pain can be treated effectively by rapid-onset opioids, such as sublingual fentanyl. However, it remained unclear how the optimal dose of sublingual fentanyl should be determined. Dosing proportional to basic opioid regimen is now proposed as an alternative to dose titration.     

Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements

Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients’ reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient’s rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms – rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.     

The role of rapid onset fentanyl products in the management of breakthrough pain in cancer patients

Breakthrough pain is defined as transient aggravation of pain that arises, despite well controlled or stable baseline pain. It may be preceded by known factors or occur spontaneously. Its prevalence is high and it considerably affects patients’ quality of life. Therefore, proper clinical evaluation and treatment is required. Fentanyl transmucosal formulations have become the treatment of choice for spontaneous (idiopathic) episodes because of their rapid onset of action, brief period of analgesia, and easy administration via transmucosal routes. All rapid onset fentanyl formulations show better efficacy than placebo or immediate-release opioids administered via the oral route, with an onset of analgesia within 15 min. Furthermore, most patients show considerable tolerance of these fentanyl formulations, and severe side effects that can potentially be induced by opioids are rarely observed. However, the treatment of breakthrough pain should be adjusted to suit specific patient requirements. Nevertheless, particularly in predictable bursts of pain and also in spontaneous episodes of breakthrough pain with slowly intensifying pain, immediate-release formulations of opioids may play an important role.     

Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer

Abstract

Objective:

To compare the efficacy of intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC), fentanyl buccal tablet (FBT) and oral morphine (OM) for the treatment of breakthrough cancer pain (BTCP).     

Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain

Abstract

Background and objectives:

Breakthrough cancer pain (BTcP) represents an important clinical challenge in the care of patients with cancer. This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl, for the treatment of BTcP in opioid-tolerant patients with cancer.     

Opioid-induced respiratory depression and risk factors in a tertiary hospital: A retrospective study

BackgroundOpioids are potent analgesics used for the treatment of moderate to severe acute and chronic cancer and non-cancer pain. However, opioid usage may be limited by negative side effects, such as potentially life-threatening respiratory depression.ObjectivesThe aim of our study is to investigate the prevalence of opioid-induced respiratory depression (OIRD) and its predictors at King Abdulaziz Medical City in Jeddah (KAMC-JD).MethodThis is a retrospective cross-sectional (chart review) study conducted from January 1, 2016, to December 31, 2020.ResultsA total of 15,753 patients received opioids during admission to KAMC-JD, and only 144 (0.915%) of them received naloxone from January 1, 2016 to December 31, 2020. Only 91 patients (0.57%) developed opioid-induced respiratory depression (OIRD), which was more frequently reported among young and middle-aged adults. OIRD was significantly associated with receiving a daily morphine milligram equivalent (MME) dose of ≥150 MME and with having a low urea concentration at the baseline and at admission under surgery. Also, fentanyl use remained a significant risk factor for OIRD.ConclusionIn conclusion, monitoring patient receiving opioids with a daily MME dose of ≥150 MME, prescribed Fentanyl, low urea concentration at the baseline, and patients’ admissions to the surgery department may mitigate the risk of developing OIRD.     

临床药师参与一例晚期肿瘤患者疼痛治疗的案例分析

目的 临床药师参与癌痛患者止痛治疗,为患者提供药学服务,保障临床安全、合理用药。方法 根据癌症晚期患者疼痛治疗原则及疼痛特点,对患者进行疼痛评估、用药教育、药学监护,并分析可能存在的药物相互作用。结果 根据三阶梯治疗原则,通过全面评估患者疼痛,加用辅助药物协同镇痛,使患者疼痛得到有效控制。同时,临床药师在患者服药期间和减量过程中均进行用药指导,对药物不良反应进行监护,发现可能存在的药物相互作用,向临床医生提出合理建议并被采纳,使患者在有效镇痛的同时得到用药安全保障。结论 临床药师参与临床疼痛治疗,为患者提供药学服务,有效地协助临床医生用药,使用药更加安全,极大地提高了患者的满意度和生活质量。     

Meta-analysis of the clinical efficacy and safety of oxycodone and morphine in cancer pain treatment

In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Internet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions (ADRs). Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale (NRS) (risk ratio [RR]: 1.04; 95% confidence interval [CI]: 0.97–1.11). Others were rated by the visual analog scale (VAS) (RR: 1.03; 95% CI: 0.97–1.10). Five studies showed that pain intensity scores did notsignificantly differ between oxycodone and morphine treatments (standard mean difference [SMD] = 0.16, 95% CI: –0.01~0.33, P = 0.06). Regarding ADRs, the incidence of constipation was lower in the oxycodone group (RR: 0.70; 95% CI: 0.58–0.85). No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.