Breakthrough Pain In Cancer Patients Research Articles

The impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl

Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

PSY26 - Costs associated with breakthrough pain in cancer patients: findings from the national breakthrough pain survey

PSY26 - Costs associated with breakthrough pain in cancer patients: findings from the national breakthrough pain survey

Fentanyl sublingual spray for breakthrough pain in cancer patients.

Breakthrough pain is a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. Typically, breakthrough pain has a fast onset and short duration, and a significant impact on patients’ quality of life. Normal-release oral opioids are the traditional pharmacological approach for patients who are receiving an around the clock opioid regimen; however, their onset and duration of action may not be suitable for treating many breakthrough pains. Efforts to provide nonparenteral opioid formulations that could provide more rapid, and more effective, relief of breakthrough pain have led to the development of transmucosal opioid formulations including fentanyl sublingual spray (FSLS). This is a formulation of fentanyl available in doses of 100, 200, 400, 600, and 800 μg strengths approved for the management of breakthrough pain in adult cancer patients already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Published pharmacokinetic, efficacy, tolerability, and safety data suggest that FSLS has a valuable role to play in the symptomatic pharmacological management of breakthrough pain. The effective dose of FSLS is determined by titration according to the needs of the individual patient.

Fentanyl for Breakthrough Cancer Pain: Where are We?

Despite relative stable and adequately controlled background pain, Breakthrough Cancer Pain (BTcP) is a transient exarcebation of pain that occurs either spontaneously or in relation to a specific predictable trigger. It is characterized by a typical temporal pattern which includes a short onset (generally a few minutes) and a short duration (30-90 minutes). It has a strong influence on quality of life (QoL), including detrimental effects on activities of daily living, sleep, social relationships and enjoyment of life. Therefore, BTcP represents an important clinical challenge in the care of patients with cancer. Transmucosal fentanyl, a rapid onset opioid (ROO), is indicated for the treatment of BTcP in patients who are already receiving and are tolerant to opioid therapy for underlying, persistent pain. In order to identify published studies on BTcP and ROOs a Medline search was carried out. The characteristics of the various formulations of transmucosal fentanyl used for BTcP and clinical data published in literature will be described in this review.

Fentanyl pectin nasal spray: a novel intranasal delivery method for the treatment of breakthrough cancer pain

Fentanyl pectin nasal spray is a novel intranasal formulation for the management of breakthrough cancer pain in patients taking and tolerant to opioids for persistent cancer pain. The pectin-based delivery modulates the product’s transmucosal absorption. Nasal delivery allows fentanyl pectin nasal spray to achieve a greater maximum plasma concentration than oral transmucosal fentanyl products and at a much faster rate. Compared with intranasal fentanyl compounded with aqueous solutions, the pectin-based system decreases the maximum plasma concentration and prolongs exposure to more closely match the time course of a typical breakthrough cancer pain episode. Throughout all phases of clinical studies, it was shown to be safe and effective in doses between 100 and 800 µg per breakthrough pain episode. Fentanyl pectin nasal spray is the only proprietary intranasal fentanyl formulation in the USA and one of two in Europe. Owing to the medication’s delivery system, the pharmacokinetics and subsequent dosing are unique to this product and should not be interchanged with any other proprietary or compounded fentanyl product.

Circadian variation of breakthrough pain in cancer patients

Breakthrough cancer pain (BTP) can place physical, psychological and economic burdens on patients and their productive life. By preventing instead of treating BTP after it occurs, the efficacy of analgesic treatment in cancer patients could be maximized. With this study, we investigated circadian variations in the occurrence of BTP events in cancer patients. The circadian variation of BTP was assessed in two different series (group 1, n = 47; group 2, n = 76) of advanced cancer patients suffering from severe chronic pain and undergoing analgesic treatment with major opioids. BTP episodes showed a circadian pattern, with an acrophase occurring at 10:00 a.m. (p < 0.001) in all patients. When the two series of patients were considered separately, an acrophase was similarly observed, with 60% of BTP episodes recorded between 10:00 a.m. and 6:00 p.m. The circadian rhythm of BTP was maintained after stratifying the patients according to whether they had bone metastases or visceral metastases. BTP episodes negatively correlated with quality of life. BTP onset follows a circadian rhythm, with an acrophase occurring in the late morning.

Nasal delivery of fentanyl.

Fentanyl, a potent opioid analgesic, is rapidly and efficiently absorbed from the nasal cavity, giving significant potential for nasally administered fentanyl to be used in pain management. Many reported clinical studies have used nasally administered IV solution, often as drops, which requires high volumes of solution to deliver an effective dose, resulting in insignificant runoff and drip which, in turn, compromises absorption and efficacy. More recently, products have been developed and commercialised with features intended to overcome these drawbacks, notably delivering the dose as a spray in a lower volume of solution and, for one of the products, incorporating an in situ gelling agent with the aim of both reducing runoff/drip and modifying the fentanyl absorption profile. The commercial fentanyl nasal spray products (PecFent/Lazanda and Instanyl) are currently licensed solely for the treatment of breakthrough pain in cancer patients; they have a number of advantages over oral transmucosal (buccal/sublingual) products used in the same indication, including faster onset of action and easier administration, especially in patients suffering from oral cavity disorders associated with cancer treatment. Given the nature of fentanyl, regulatory agencies will expect that appropriate safety features are incorporated into the primary and secondary packaging in products intended for use by patients in the home and may also impose risk management protocols to control the distribution and prescription of controlled substances. These demands notwithstanding, intranasal fentanyl offers much future promise, including for additional indications and paediatric use.

Fentanyl Pectin Nasal Spray for Breakthrough Cancer Pain

Optimal management of breakthrough cancer pain (BTCP) requires analgesics with a rapid onset of action, consistent efficacy, improved patient acceptability and tolerability and ease of use. Fentanyl pectin nasal spray (FPNS) incorporates a proprietary pectin-based gelling agent to enhance absorption and produce a faster onset of action and consistent plasma concentration. FPNS is indicated for the treatment of breakthrough pain in cancer patients who are tolerant to opioid therapy for their underlying persistent cancer pain. FPNS has been evaluated in clinical studies in patients with BTCP and shown to be effective, safe and well tolerated. In addition, FPNS has demonstrated high levels of patient satisfaction, convenience and ease of use. FPNS therefore represents an important addition to the treatment options for BTCP.

Intranasal fentanyl in the treatment of acute pain – a systematic review

Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric population. The objective of this systematic review was to evaluate the current evidence of IN fentanyl in the treatment of acute pain. Reports of randomized controlled trials (RCTs) of IN fentanyl in treatment of pain were systematically sought using the PubMed database, Embase, Google scholar, Cochrane database, and Cumulative Index to Nursing and Allied Health Literature. Reports were considered for inclusion if they were double-blinded randomized controlled trials (RCTs) of IN fentanyl in the treatment of acute pain. Thirty-two RCTs were identified, and 16 were included in the final analysis. No significant analgesic differences between IN fentanyl and intravenous (IV) fentanyl were demonstrated in treatment of acute and post-operative pain. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. In the paediatric population, results demonstrated some analgesic effect of IN fentanyl following myringotomy, no analgesic effect following voiding cystourethrography, and finally, no significant analgesic difference after long bone fractures, in burns patients, and in post-operative pain relief when compared to IV morphine, oral morphine, or IV fentanyl, respectively. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. However, the significant deficiencies in trials investigating acute and post-operative pain, and the paediatric population makes firm recommendations impossible.

Chinical diagnosis and therapy of breakthrough pain in cancer patients

Blackground Breakthrough pain (BTP) is a transient exacerbation of pain with moderate and severe intensity and has high incidence in patients with cancer. Breakthrough pain lacks a consensus international definition and diagnosis standard,and clinical treatment of which is subsequently inadequate. Therefore it is difficult to manage breakthrough pain in patients with cancer. Objective This article is to summed up the newest development about the diagnosis and treatment of breakthrough pain in order to provide the evidence for clinical management. Content The diagnosis of breakthrough pain includes definition,epidemiology, classification and evaluation. However, management of breakthrough pain involves pharmacological and nonpharmacological treatment. Trend The most common therapy of breakthrough pain is administration of short and quick analgesics. However, the ideal management of breakthrough pain may require a combination of pharmacological with nonpharmacological treatment strategies. Key words: Cancer; Breakthrough pain; Diagnosis; Management

Fentanyl nasal spray for the treatment of cancer pain

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.

Characteristics of breakthrough cancer pain in patients treated with fentanyl sublingual tablets: An analysis of two phase III trials.

e19593 Background: Breakthrough cancer pain (BTcP), a transient pain exacerbation occurring in cancer patients with otherwise stable persistent pain levels, negatively impacts quality of life (QoL)...

Evaluation of fentanyl buccal soluble film (FBSF) in opioid tolerant cancer patients with neuropathic breakthrough cancer pain (BTP)

Neuropathic pain, in particular neuropathic breakthrough cancer pain (BTP), is poorly understood and difficult to effectively control. Pain clinicians generally use agents that are not ordinarily used as analgesics, such as anticonvulsants and antidepressants, alpha-2 adrenergic agonists and NMDA receptor antagonists in combination with opioids as treatments. In 2009, a fentanyl buccal soluble film (FBSF) was approved for the management of BTP in opioid-tolerant cancer patients ≥18 years of age. The safety and efficacy of FBSF was studied in a multicenter, randomized, double-blind, placebo-controlled, multiple-crossover study in adult cancer patients on stable opioid therapy who reported ≤4 BTP episodes per day. A subgroup of patients from that trial was analyzed to evaluate the efficacy and safety of FBSF in patients with neuropathic BTP pain. The primary variable evaluated was the sum of pain intensity differences (SPID) at 30 minutes with higher scores correlating with greater pain relief. Adverse events were recorded and summarized. Fourteen females and nine males (mean age ∼51 years) were included in the subgroup analysis and breast cancer (n=6) was the most prevalent type of cancer among these patients. Pain reduction after treatment with FBSF was greater than after treatment with placebo. SPID values in patients with neuropathic BTP were significantly higher for FBSF-treated episodes than for those episodes treated with placebo beginning 15 minutes after dosing. FBSF was as effective in this subgroup as in the entire population. The most commonly reported adverse events included somnolence, nausea, and dizziness. The results of this subgroup analysis indicate that FBSF may aid in the management of breakthrough cancer pain in patients experiencing neuropathic pain. This subgroup analysis was supported by a grant from Meda Pharmaceuticals, Inc.

PecFent: gel‐based nasal fentanyl for breakthrough cancer pain

AbstractPecFent is a new intranasal formulation of fentanyl licensed for the management of breakthrough pain in cancer patients receiving opioid therapy. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse effects and Drs Monica Chogle and William Campbell comment on its place in breakthrough pain management. Copyright © 2011 Wiley Interface Ltd

Breakthrough Pain in Cancer Patients

Breakthrough pain is a transient exacerbation of pain that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. A typical episode of breakthrough pain has a fast onset and short duration, yet despite the self-limiting nature of each breakthrough pain, the repeated episodes can have a significant effect on patients’ quality of life. Normal-release oral opioids have been the mainstay pharmacological approach for patients who are receiving an around the clock opioid regimen, but the onset and duration of action of oral opioids such as morphine may not be suitable for treating many breakthrough pains. Efforts to provide non-parenteral opioid formulations that could provide more rapid, and more effective, relief of breakthrough pain have led to the development of transmucosal opioid formulations.

Breakthrough Pain in Cancer Patients— Characteristics, Impact, and Assessment

Breakthrough pain (brief flares of severe pain superimposed on baseline pain) is a common problem in patients with cancer and is associated with significant physical, psychologic and economic burdens on patients and carers. The successful management of breakthrough pain is dependent on the accurate diagnosis and adequate assessment of the patient, which in turn leads to appropriate and effective treatment. It is clear that the impact of breakthrough pain on patients is wide ranging, affecting patient quality of life, decreasing physical functioning, and often leading to psychologic consequences, such as anxiety and depression. A structured and appropriate approach to the assessment and diagnosis of breakthrough pain needs to be comprehensive to identify all the areas of impact on a patient’s life. In this article, cancer breakthrough pain is defined and the different subtypes of breakthrough pain are explained. Assessment tools that are frequently used to appropriately assess the effects of breakthrough pain are discussed and treatment options after diagnosis are also outlined, with a focus on non-pharmacologic interventions.

Breakthrough Pain in Cancer Patients— Pharmacologic Symptomatic Treatment

Breakthrough pain is experienced by many cancer patients who are being treated with opioids for the management of chronic persistent pain. There is currently no ‘gold standard’ approach for the pharmacologic symptomatic treatment of breakthrough pain but proposed strategies include the implementation of primary therapies (e.g. chemotherapy, radiotherapy, and surgery) for the underlying cause of the pain; optimization of scheduled analgesia; use of adjuvants; and specific supplemental analgesia for breakthrough pain (the most common pharmacologic strategy). Individualization of treatment is important and a combination of these strategies may be required. In this article, pharmacotherapeutic approaches to managing breakthrough pain are discussed, including different routes of administration and newer opioid formulations. In addition, the current guidelines for managing breakthrough pain are examined.

Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 – 800 µg in healthy volunteers

Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing PecSys®; pectin based enabling technology (Archimedes). On contact with the nasal mucosa the formulation will gel and modulate fentanyl absorption while limiting nasal drip or runoff. This single-dose volunteer study compared the pharmacokinetics of FPNS 100, 200, 400, and 800 µg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 µg. Safety and dose proportionality were also examined. 16, opioid-naïve subjects were dosed on five separate visits under naltrexone block. FPNS doses were administered using a Pfeiffer device delivering 100 µl. Devices were filled with either 1.57 mg/ml (100 and 200 µg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 µg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. Median tmax values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 µg Cmax values were 2.3-fold higher for FPNS compared with OTFC. Mean relative bioavailability of FPNS to OTFC ranged from 103% to 163%. Dose proportionality for Cmax and AUC0-1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC0-inf. FPNS has a shorter tmax, higher Cmax and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC0-1 was demonstrated. It is concluded that the pharmacokinetic profile of FPNS suggests this product is suitable for clinical investigation in breakthrough pain in cancer patients.

The use of fentanyl buccal tablets as breakthrough medication in patients receiving chronic methadone therapy: an open label preliminary study

Data on the treatment of breakthrough cancer pain (BTcP) in patients receiving methadone therapy are lacking. Whether methadone produces tolerance to other opioids, other opioids should be less effective when administered as a BTcP medication. The aim of this preliminary study was to assess the efficacy of fentanyl buccal tablets (FBT) for the treatment of BTcP in patients who receive methadone as a background analgesic. A prospective study was carried out for a period of 1 year in a consecutive sample of 13 advanced cancer patients admitted to an acute pain relief and palliative care unit-patients who were receiving stable doses of oral methadone for their background analgesia. The dose of FBT was 100 μg for patients who were receiving 12 mg of oral methadone. For higher doses of methadone, proportional doses of FBT were given. For each episode, trained nurses collected changes in pain intensity (on numerical scale 0-10) and emerging problems when called for pain increases considered to be severe in intensity by patients) (T0) and 15 min after FBT administration (T15). The mean age was 58.1 (SD 9.9), and nine patients were males. Sixty-four events were treated with FBT (4.9 ± 3.1 for each patient, on average). Patients were receiving mean doses of oral methadone of 68 mg (range 15-240). In the majority of events, a decrease in pain intensity >33% and >50% was observed (n = 20 and n = 26, respectively), 15 min after the administration of FBT. Data on ten episodes were unavailable. Nine events were unsuccessfully treated. In all the patients, the level of adverse effects after FBT administration was mild and undistinguishable from that associated with basal opioid analgesia. FBT was effective as breakthrough pain medication in patients receiving methadone for their background analgesia, confirming that this group of patients are not inevitably resistant to other opioids.

Breakthrough Pain in Oncology: A Longitudinal Study

Existing studies on breakthrough pain (BP) have reported different prevalence rates because of different settings, populations, and assessment methods. These studies have used cross-sectional designs, and the relationship of BP with analgesic treatment has not been evaluated. The aim of this study was to longitudinally assess BP in cancer patients admitted to oncology units. A consecutive sample of patients admitted to oncology centers was selected. At admission (T0), three months after admission (T3), and six months after admission (T6), data on background pain and BP were recorded. BP was assessed in terms of its intensity, duration, number of episodes, onset with movement, spontaneous relief after stopping activity, limitation of physical activity, and effectiveness of analgesics. Three hundred two patients completed the study. At T0, T3, and T6, 39%, 38%, and 33% patients, respectively, had continuous pain (P=0.294). Pain intensity significantly decreased (P=0.004 and 0.027 at T3 and T6, respectively). Most patients had BP at T0 (87.1%), T3 (80.9%), and T6 (73.2%), and there was a significant decrease in the prevalence of BP over time (P=0.016). Of 149 patients with BP, pain on movement was recorded in 43.6%, 43.4%, and 32.4% at T0, T3, and T6, respectively (P=0.228). Pain spontaneously decreased or ceased when stopping physical activity in 66%, 56%, and 62% at T0, T3, and T6, respectively (P=0.537). Pain on movement strongly limited physical activity in most patients. These data expand current information about BP and underline the need for a longitudinal assessment of a phenomenon that is invariably dependent on stage of disease, patient, and therapeutic factors.