Safety Of Fentanyl Buccal Tablet Research Articles

Fentanyl buccal tablet for breakthrough cancer pain in clinical practice: results of the non-interventional prospective study ErkentNIS

PurposeSeveral patients with advanced cancer suffer from breakthrough cancer pain (BTcP). BTcP is pain exacerbation despite opioid baseline therapy. Fentanyl buccal tablet (FBT) is a rapid-onset opioid for the treatment of BTcP. The aim of this study is to document the feasibility of FBT in patients with BTcP.MethodsThe study was performed in 64 centers. Basic pain score was rated on a numeric rating scale (NRS) before and after treatment. BTcP episodes, baseline opioid therapy, and FBT dose were rated as well as individual dose titration, findings on tolerability, patient satisfaction, and safety of the drug.ResultsTwo hundred sixty-three patients were available for analysis. Patients rated a basic pain score of 6 (range 2–10) points on an NRS and described an average of 2 to 5 BTcP episodes per day. After titration of FBT, BTcP control was achieved within 5 min in 36%, within 10 min in 68%, and within 15 min in 95%. Basic pain score decreased to a mean NRS of 4 and BTcP episodes decreased to < 1 to 3 episodes per day. BTcP control, onset of action of FBT, potency of FBT, tolerability of FBT, and safety of FBT were rated as excellent or good by 89 to 99% of the patients. Adverse drug reactions were registered in 3%.ConclusionsTreatment with FBT led to rapid pain relief and reductions in the number of BTcP episodes and patient satisfaction was rated as excellent or good.

The Efficacy and Safety of Fentanyl Buccal Tablet Compared with Immediate-Release Oxycodone for the Management of Breakthrough Pain in Opioid-Tolerant Patients with Chronic Pain

Current clinical guidelines have identified the need for studies comparing the effect of different short-acting or rapid-onset opioids for the treatment of breakthrough pain (BTP). In this study we evaluated the efficacy and safety of treatment with fentanyl buccal tablet (FBT) in comparison with immediate-release oxycodone in alleviating BTP in opioid-tolerant patients with chronic pain. In this cross-over design study, opioid-tolerant patients were randomized to open-label titration with FBT (200, 400, 600, 800 μg) followed by oxycodone (15, 30, 45, 60 mg) or vice versa for the management of BTP. After titration to a successful dose of both study drugs, patients were rerandomized to double-blind treatment for 10 BTP episodes with 1 of the already identified successful doses of study drug followed by cross-over to double-blind treatment for 10 BTP episodes with the other study drug. The primary efficacy measure was the difference in pain intensity (based on an 11-point numerical scale) 15 minutes after administration of study drug (PID(15)). Other efficacy measures included PID at other time points postdose (5 through 60 minutes), the sum of pain intensity differences (SPID) at 30 and 60 minutes postdose, pain relief (5 through 60 minutes), proportion of BTP episodes for which patients experienced meaningful reduction in pain intensity, and patient preference for BTP medication. Adverse events were also recorded. Of the 323 patients enrolled, 203 achieved a successful dose of both study drugs, 191 completed the titration phase, and 180 completed the double-blind phase. PID(15) was significantly greater after FBT versus oxycodone (mean [SD], 0.82 [1.12] vs. 0.60 [0.88]; 95% confidence interval [CI] = 0.18, 0.29; P < 0.0001). Secondary efficacy measures favored FBT and showed differences versus oxycodone from 5 minutes postdose for PID and 10 minutes postdose for pain relief. SPID(30) and SPID(60) were greater with FBT than with oxycodone (P < 0.0001 for both measures). A ≥33% improvement in pain intensity occurred in a larger proportion of FBT-treated episodes versus oxycodone beginning 15 through 45 minutes postdose (P < 0.05). FBT was preferred by 52% of patients, oxycodone by 33%. Adverse events with both study drugs were generally typical of opioids, and the majority occurred during titration. Two serious adverse events (pneumonia) were reported in 1 patient; both occurrences were considered unrelated to study drug. FBT resulted in more rapid onset of analgesia and was generally well tolerated in comparison with oxycodone for the treatment of BTP in opioid-tolerant patients.

A Novel 12-Week Study, with Three Randomized, Double-Blind Placebo-Controlled Periods to Evaluate Fentanyl Buccal Tablets for the Relief of Breakthrough Pain in Opioid-Tolerant Patients with Noncancer-Related Chronic Pain

To evaluate the time of onset, overall efficacy, and safety of fentanyl buccal tablet (FBT) for noncancer-related breakthrough pain (BTP) in opioid-tolerant adults over 12 weeks. A novel 12-week study that mimicked clinical practice with dose titration to effective dose, open-label treatment, and three randomized, double-blind, placebo-controlled, multiple-crossover periods at weeks 4, 8, and 12. For each double-blind period, study patients received nine doses (FBT = 6, placebo = 3) in a randomized sequence. Twenty-one study centers in the United States. Opioid-tolerant adults with noncancer-related chronic pain and BTP. The primary outcome was the sum of the pain intensity differences (PID) 5-60 minutes post dose (SPID₆₀) during the final double-blind period. Secondary outcomes included pain relief (PR), meaningful PR, and proportion of episodes with a PID of ≥33% and ≥50%. Of 148 patients who entered the titration phase, 105 (71%) achieved a successful dose and 81 (55%) participated in all three assessment periods in the study. The final RCT assessment period results demonstrated continued efficacy of FBT vs placebo (P < 0.05) for SPID₆₀ (mean [SD]: 7.7 [6.2] vs 4.6 [4.7]). The average onset of PR began at 5 minutes, with meaningful PR by ≤10 minutes. The proportion of episodes with ≥33% improvement in PI was 7% with FBT vs 3% with placebo at 5 minutes and with ≥50% was 17% vs 10% at 15 minutes. All periods showed similar results. Adverse events and patient discontinuations were generally typical of clinical opioid use. FBT showed continued clinically important analgesic effects and was generally well tolerated over 12 weeks of treatment.

Poster 191: Efficacy, Safety, and Tolerability of Fentanyl Buccal Tablet in Opioid-Tolerant Patients With Chronic Cancer Pain and Breakthrough Pain

Objective: To evaluate the efficacy and safety of a fentanyl buccal tablet (FBT) for the management of breakthrough pain in opioid-tolerant patients with chronic cancer pain. Design: Double-blind, randomized, placebo-controlled study. Setting: 30 centers in the United States. Participants: 129 enrolled patients; 70% (87/125) identified an effective FBT dose (100, 200, 400, 600, or 800μg) during initial open-label dose titration. Interventions: Patients self-administered prespecified sequences of 10 tablets (7 FBT, 3 placebo).

Efficacy and tolerability of fentanyl buccal tablet (FBT) in opioid-tolerant cancer patients with neuropathic pain

19549 Background: Fentanyl buccal tablet (FBT), a new formulation recently approved by the FDA for opioid-tolerant patients with cancer-related breakthrough pain (BTP), provides rapid-onset analgesia. Neuropathic pain is the primary pain pathophysiology in a significant proportion of patients with chronic cancer pain; therefore, the efficacy and safety of FBT was studied in this subpopulation. Methods: The efficacy and safety of FBT in the treatment of BTP in opioid-tolerant cancer patients with neuropathic pain were evaluated as a sub-analysis of two randomized, double-blind, placebo-controlled studies. Of the 45 patients in the sub-analysis (50% male, 86% white, mean age 56 years), 30 identified an effective FBT dose during open-label titration and were randomly assigned to double-blind crossover dose sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) and pain relief (PR) were recorded at intervals after dosing. The primary efficacy measures were the sum of pain intensity differences (PIDs) for the first 30 (SPID30) and 60 minutes (SPID60); secondary efficacy measures included PIDs, PR, and total pain relief (TOTPAR). Use of supplemental BTP medication and adverse events (AEs) were recorded. Results: Combined data (all values mean ±SD) favored FBT vs placebo for SPID30 (3.35±3.11 vs 1.88±2.58) and were significant for SPID60 (9.90±7.19 vs 5.51±6.06; 95% CI, 2.99, 5.81). There was a greater reduction in PI following FBT vs placebo at 10 minutes (PID, 0.55±0.89 vs 0.24±0.48), which continued through observation periods of up to 2 hours (3.43±2.44 vs 1.95±1.99). Higher PR scores were noted following FBT vs placebo at 10 minutes (0.43±0.39 vs 0.21±0.28), which continued for up to 2 hours (1.99±0.72 vs 1.36±0.60). TOTPAR was better following FBT vs placebo at 15 (0.88±0.89 vs 0.48±0.73), 30 (2.42±1.85 vs 1.40±1.65), 45 (4.29±2.90 vs 2.61±2.68), and 60 minutes (6.34±4.02 vs 3.94±3.81). Patients were more than twice as likely to require supplemental opioids for BTP episodes following placebo vs FBT. AEs were typical for opioids; e.g., headache (23%), nausea (18%), dizziness (18%), vomiting (14%), and fatigue (11%). Conclusions: FBT was effective and well tolerated in a subgroup of cancer patients with BTP in association with chronic neuropathic pain. No significant financial relationships to disclose.

A double-blind, randomized, placebo-controlled study of fentanyl buccal tablet (FBT) in opioid-tolerant patients with chronic cancer pain and breakthrough pain

9057 Background: Episodes of cancer-related breakthrough pain (BTP) often peak in intensity in minutes. Pain relief with traditional, short-acting oral opioids is often not achieved for =30 min. Fentanyl buccal tablet (FBT) has a rapid onset of analgesia. This double- blind, randomized, placebo-controlled study evaluated the efficacy and safety of FBT in opioid-tolerant patients with cancer and BTP. Methods: After open-label titration to establish a successful dose of FBT, patients were randomized to prespecified, double-blinded sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) was assessed from 5 to 120 min post dose. The primary efficacy measure was the sum of PI differences (PIDs) for the first 60 min (SPID60); secondary measures included PIDs, =33% and =50% improvements in PI, and global medication performance (GMP). Use of supplemental BTP medication and adverse events (AEs) were reported. Results: 129 patients were enrolled; 87/125 treated (70%) identified an effective FBT dose and entered the double-blind phase. SPID60 significantly favored FBT vs placebo (mean±SEM, 9.7±0.63 vs 4.9±0.50; p&lt;0.0001). PID differed significantly vs placebo at 10 min (mean±SEM, 0.9±0.09 vs 0.5±0.09; p&lt;0.0001) and at all time points through 2 hr (p&lt;0.0001). Improvements in PI of =33% and =50% from baseline occurred in a larger proportion of episodes following FBT vs placebo from 10 min (16% vs 10% and 7% vs 4%, respectively; p&lt;0.05) through 2 hr (74% vs 38% and 66% vs 28%; p&lt;0.0001). Ratings of GMP were superior for FBT vs placebo at 60 and 120 min (p&lt;0.0001). Supplemental opioids were required for approximately 3 times more BTP episodes following placebo compared with FBT. AEs were typical for opioids, e.g. nausea (13%), dizziness (11%), fatigue (8%), and constipation (6%). Application site-related AEs occurred in 12 patients (10%). A total of 11/125 (9%) patients had =1 serious AE; these were considered not/unlikely to be related to study drug. Conclusions: FBT was effective and well tolerated in the management of BTP in opioid-tolerant patients with cancer-related pain, with an early onset of analgesia and a sustained duration of effect. No significant financial relationships to disclose.

(760): Management of beakthrough pain in opioid-tolerant patients with chronic low back pain or neuropathic pain: Randomized, double-blind Studies of efficacy and tolerability of fentanyl buccal tablet (FBT)

Treating breakthrough pain (BTP) with opioids is well established in chronic cancer pain; extension of this approach to noncancer pain is increasing. However, the time to peak intensity of BTP precedes the onset of analgesia with short-acting opioids. FBT is designed to provide rapid-onset analgesia and may address this problem. The efficacy and safety of FBT in the management of BTP were examined in opioid-tolerant, noncancer patients with chronic, persistent neuropathic pain (Study 1) or chronic, persistent low back pain (Study 2). Patients identifying an effective FBT dose (100-800 μg) during a titration phase (Study 1, 80/102; Study 2, 84/104) entered a double-blind phase to treat 9 BTP episodes (6 with FBT, 3 with placebo). Pain intensity (PI; 11-point scale) was measured through 2 hours. The primary efficacy measure was the time-weighted sum of pain intensity differences (PIDs) for the first 60 minutes (SPID60). In both studies, SPID60 was significantly better with FBT than placebo (Study 1, mean±SE: 9.6±0.75 vs 5.7±0.72, P<0.0001; Study 2, 8.3±0.66 vs 3.6±0.57, P<0.0001). PIDs were significantly greater after FBT vs placebo at 10 minutes (Study 1, P=0.0463; Study 2, P=0.0184) and each subsequent time point (P<0.01). The proportion of BTP episodes with ≥33% improvement in PI significantly favored FBT beginning at 10 (Study 1) and 15 minutes (Study 2, P<0.01 for both). In the pooled safety analysis (N=206), AEs were typical of opioids (e.g., nausea, dizziness, and somnolence); more were reported during the dose titration (55%) than double-blind phase (31%). Thirteen patients (6%) experienced application-site AEs, the majority of which were mild; all resolved without residual effect. A total of 24 patients (12%) discontinued due to AEs. In conclusion, results of two studies of noncancer pain were consistent in showing that FBT was effective and well tolerated in the management of opioid-tolerant patients with BTP.