Fentanyl buccal tablet.
ABSTRACT Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.
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ABSTRACT: The purpose of this article is to systematically review the use of fentanyl as an analgesic for breakthrough pain. This article found that the oral transmucosal fentanyl (OTFC) had a quicker onset to analgesia than oral immediate-release opioids. Intranasal fentanyl (INFS) had a quicker onset to analgesia than buccal tablets, which in turn had a quicker onset to analgesia than OTFC. Patient acceptance and global rating of efficacy were greater for INFS than for buccal fentanyl. OTFC and INFS have been used effectively to reduce acute pain in children who are opioid-naive. Abuse and addiction to OTFC, fentanyl buccal tablets and INFS was low, owing to patient selection.Expert Review of Neurotherapeutics 08/2011; 11(8):1197-216. · 2.96 Impact Factor
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ABSTRACT: INTRODUCTION: Breakthrough pain, a transitory flare of pain in patients with otherwise controlled chronic pain, has been well characterized in cancer patients but despite medical awareness, sometimes remains underdiagnosed and therefore undertreated. AREAS COVERED: Oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablets are the first medications developed specifically for the treatment of breakthrough pain in opioid-tolerant patients. Since oral administration of fentanyl is not an option for many cancer patients, the development of intranasal fentanyl spray (INFS) emerged as a more effective method of administration. Intranasal administration of fentanyl has several advantages over the oral/gastrointestinal route and clinical trials have shown that it is superior to OTFC while being well tolerated and more acceptable by the majority of patients. EXPERT OPINION: The aim of this review is to summarize the pharmacological characteristics and data obtained from clinical studies of INFS in the past few years, and present Fentanyl Pectin Nasal Spray (PecFent), which uses an innovative delivery system and is now approved in the EU. Finally, we discuss the impact that it may have in the future management of breakthrough pain in cancer patients, because an accurate diagnosis followed by the best treatment is crucial for effective pain alleviation.Expert Opinion on Pharmacotherapy 07/2011; 12(10):1653-9. · 2.86 Impact Factor
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ABSTRACT: In controlled trials, dual therapy with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) is associated with hyperkalemia and decreased renal function, but there is no information about these adverse effects in clinical practice. The aim of this study was to assess the incidence of hyperkalemia and decreased renal function during dual therapy (ACE-I plus ARB) in a community-based setting. In a retrospective cohort database study, we identified patients who received ARBs added to ongoing ACE-I therapy and who had at least 1 measurement of serum creatinine and potassium during each treatment period. We compared rates of hyperkalemia (>5.5 mmol/L) during equal periods of monotherapy and dual therapy and the rate of a significant rise in serum creatinine (≥0.5 mg/dL) between study periods. We assessed the impact of potential confounders on outcomes by logistic regression analysis. Among 425 patients (median follow-up 19 months for each treatment period), hyperkalemia was 2-fold more common during dual therapy than monotherapy (11.1% and 5.6% of patients, respectively) (relative risk = 1.96; 95% CI, 1.22-3.14; P < 0.001). In 77 patients with reduced renal function on monotherapy (serum creatinine ≥1.5 mg/dL), the rate of hyperkalemia was 20.8/100 patient-years, resulting in a number needed to harm of 10.1 patients, compared with 52.6 patients among those with preserved renal function. Mean serum creatinine between treatment periods increased >0.5 mg/dL in 7.5% of patients, more commonly in patients with decreased (18.2%) than with preserved (5.2%) baseline renal function (P < 0.001). In the community setting, dual therapy was associated with hyperkalemia and a decrease in renal function. The absolute risks were especially high among patients with reduced baseline renal function.Clinical Therapeutics 04/2011; 33(4):456-64. · 2.23 Impact Factor