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.     

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.     

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.     

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.     

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).     

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.     

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.     

Oral transmucosal fentanyl citrate: overview of pharmacological and clinical characteristics

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq®, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.     

Clinical pharmacology of fentanyl buccal tablet for the treatment of breakthrough pain

Fentanyl buccal tablet (FBT) is a new formulation of fentanyl providing rapid-onset analgesia for the treatment of breakthrough pain. FBT has been approved for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for underlying persistent pain. FBT has demonstrated a favorable pharmacokinetic profile, which is closely aligned to the rapid onset and duration of an episode of breakthrough pain, and is generally safe and well tolerated.     

Relationship between background cancer pain,breakthrough pain,and analgesic treatment: a preliminary study for a better interpretation of epidemiological and clinical studies

Abstract

Background:

The different operational definitions of breakthrough cancer pain (BTcP) has generated unclear epidemiological data.     

Pharmacokinetics and tolerability of different doses of fentanyl following sublingual administration of a rapidly dissolving tablet to cancer patients: a new approach to treatment of incident pain

AIMS: It is estimated that two-thirds of cancer patients will at some point during their illness experience breakthrough pain. In this study, the pharmacokinetics of a novel sublingual dosage form of fentanyl developed for breakthrough pain was evaluated. METHODS: Eleven Caucasian patients (seven male and 4 female, aged 34-75 years, median 60 years) with metastatic malignant disease were recruited initially, but three patients withdrew. Prior to the study all patients were on continuous nonfentanyl opiate medication. The study was a double-blind, cross-over trial, consisting of three 1-day treatment periods. A new rapidly dissolving preparation of fentanyl, was administered sublingually in single doses of 100, 200 and 400 microg, respectively, on three separate occasions. Plasma fentanyl concentrations were determined using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated by noncompartment analysis. Tolerability and the occurrence of adverse events were monitored throughout the study by patient questionnaire. RESULTS: The data from nine subjects who completed at least two periods were used in the analysis of variance. There were no significant differences between doses (100, 200 and 400 microg) for dose adjusted AUC (F = 0.42, P = 0.6660), dose adjusted C(max) (F = 0.08, P = 0.9206) and Tmax (F = 0.94, P = 0.4107). Thus, these parameters showed dose proportionality. The differences (400-100microg) in dose adjusted AUC from the three-period crossover analysis was -0.016 min.ng/ml (t = 0.71, P = 0.8718). Interindividual variability in systemic exposure to fentanyl was fairly small (25-40%), which may be related to a good in vivo biopharmaceutical performance of the sublingual tablet, and a relatively small fraction of the dose being swallowed. The first detectable plasma concentration of fentanyl was observed between 8 and 11 min after administration. t(max) increased from 39.7 +/- 17.4 to 48.7 +/- 26.3 and 56.7 +/- 24.6 min for the 100, 200 and 400 microg doses, respectively. Adverse events were few and did not increase with increasing dose. CONCLUSION: With this rapidly dissolving fentanyl formulation, the first detectable plasma concentration of fentanyl was observed at 8-11 min after administration. The pharmacokinetics of the drug showed dose proportionately. This formulation of fentanyl seemed to be well tolerated by the patients.     

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.     

骨架扩散型芬太尼透皮贴剂对中重度癌性疼痛的镇痛效果及安全性评价

目的探讨骨架扩散型芬太尼透皮贴剂对中重度癌性疼痛的镇痛效果及不良反应发生情况。方法选择我院收治的中重度癌性疼痛的患者为研究对象,随机分为观察组和对照组。观察组应用骨架扩散型芬太尼透皮贴剂进行镇痛,对照组应用储库型芬太尼透皮贴剂进行镇痛。对比分析两组患者的镇痛效果、不良反应发生情况、生活质量改善情况及用药满意度。结果两组患者用药后1个月,VAS评分均较治疗前明显改善,差异有统计学意义(P<0.01),而两组用药后VAS评分比较差异无统计学意义(P>0.05);观察组疼痛完全缓解率及总有效率略高于对照组,但差异均无统计学意义(P>0.05)。观察组患者满意度明显高于对照组,差异有统计学意义(P<0.05)。观察组皮疹、水疱的发生率明显低于对照组,差异有统计学意义(P<0.05),两组其余不良反应的发生率比较差异无统计学意义(P>0.05)。用药1个月后,两组FACT-G总评分均较治疗前明显升高,差异均有统计学意义(P<0.01),两组比较差异无统计学意义(P>0.05)。结论新型的骨架扩散型芬太尼透皮贴剂对中重度癌性疼痛镇痛效果良好,与传统储库型芬太尼透皮贴剂相比,具有起效快,皮肤耐受性、黏合性、舒适度好等优点,更易于患者接受,且具有良好的安全性,值得临床推广应用。     

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).     

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.     

Oral Transmucosal Fentanyl Citrate: Overview of Pharmacological and Clinical Characteristics

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq®, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.