Transmucosal Immediate-release Fentanyl Research Articles

The Prevalence of Off-label Prescribing of Transmucosal Immediate-Release Fentanyl in France

ContextThe abuse of opioids and opioid-related harms, including deaths, in the United States are well documented. In the European Union, opioid use has also been increasing, particularly of fentanyl. ObjectiveWe assessed the prevalence of off-label prescribing of transmucosal immediate-release fentanyl (TIRF), in France, in 2019. We looked at the patients’ and prescribers’ characteristics and compared the population of patients who received TIRF in off-label prescriptions with those taking it on-label. We also examined the differences between the patients with and without cancer in the off-label use population. MethodsThis was a population-based cross-sectional study conducted in 2019, using the French national insurance claims database Système National d'Informations Inter-Régimes de l'Assurance Maladie, covering 98.8% of the French population, or 66 million people. ResultsWe selected 224,000 patients with fentanyl prescriptions. Among them, 23,209 had at least one TIRF delivered. The median age was 71 years (59-85) and most patients were female (55.8%). The prevalence of off-label prescribing of TIRF was 51.8% (n = 12,031), corresponding to 9827 patients not diagnosed with cancer. The three main pharmaceutical TIRF specialties prescribed in two groups were Abstral, Pecfent, and Instanyl. Overall, TIRF was mainly prescribed by private general practitioners (64.8%). ConclusionThe prevalence of off-label prescribing of TIRF in France is extremely high. A field survey is now needed 1) to better understand why TIRF is used in conditions not indicated in its marketing authorization, and in what clinical situations, and 2) to determine whether the benefit/risk ratio of such use is favorable.

Med Check: Rapid Blood Test for Concussion; REMS for Some Fentanyl Products; Phase 3 for Troriluzole for OCD; Remote Neuromodulation Device for Adolescent Migraine

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Rapid Blood Test for Concussion; REMS for Some Fentanyl Products; Phase 3 for Troriluzole for OCD; Remote Neuromodulation Device for Adolescent MigraineTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:10 Feb 2021https://doi.org/10.1176/appi.pn.2021.2.1FDA Approves Rapid Blood Test for ConcussionsIn January the FDA approved Abbott’s i-STAT Alinity handheld device for detecting mild traumatic brain injury (TBI), the company announced. Test results are available within 15 minutes using plasma that is placed into a test cartridge. The test was developed in collaboration with the U.S. Department of Defense.The test measures glial fibrillary acidic protein and ubiquitin carboxyl-terminal hydrolase L1 in blood plasma—two biomarkers that indicate brain injury when they are elevated. According to a statement by the company, the device provides test results with 95.8% sensitivity and greater than 99% negative predictive value. A negative test can rule out the need for a CT scan, and having a blood test available could reduce the number of unnecessary CT scans, according to the company.FDA Toughens REMS for Some Fentanyl ProductsIn December the Food and Drug Administration (FDA) took steps to strengthen the Risk Evaluation and Mitigation Strategy (REMS) program for transmucosal immediate-release fentanyl (TIRF).“To use the TIRF medicines safely, these patients must be opioid tolerant based on concurrent regular use of another opioid medication,” the FDA wrote in a statement. “Despite the decline in the use of TIRF medicines in recent years, data have suggested that prescribing of TIRF medicines still occurs in patients who are not opioid tolerant. With this in mind, the FDA finalized modifications to the REMS program to address the persistence of these concerning prescribing practices.”The TIRF REMS program now requires the following:Prescribers must document a patient’s opioid tolerance with each prescription of a TIRF medicine for outpatient use.Outpatient pharmacies dispensing TIRF medicines must document and verify a patient’s opioid tolerance before dispensing.Inpatient pharmacies must develop internal policies and procedures to verify opioid tolerance in patients who require TIRF medicines while hospitalized.A new patient registry will monitor for accidental exposure, misuse, abuse, addiction, and overdose.Phase 3 Trial Enrollment Begins for Troriluzole for OCDBiohaven has begun enrollment for a phase 3 trial to assess the efficacy and safety of 280 mg troriluzole once per day in patients with obsessive-compulsive disorder (OCD), the company announced in January. The trial will include two double-blind, placebo-controlled studies with approximately 600 patients in each. Troriluzole normalizes synaptic levels of glutamate, a key neurotransmitter implicated in OCD.Biohaven is pressing forward with the phase 3 trial even though troriluzole did not meet its primary endpoint in a previous trial, wherein scores on the Yale-Brown Obsessive-Compulsive Scale for patients who took troriluzole were not statistically significantly better than those who took placebo after 12 weeks. In the previous trial, scores in patients who took troriluzole dropped an average of 5.9 points from baseline, compared with 4.9 points in those who took placebo. However, after eight weeks, there was a 1.5-point gap in scores between the troriluzole group and the placebo group.Remote Neuromodulation Device Shows Promise For Adolescent MigraineA study in Headache suggests that Nerivio, a wearable device approved for treating migraine in adults, may also be helpful in treating the condition in adolescents, manufacturer Theranica announced in December. The device, which is worn with an arm band and controlled through an app on the patient’s smartphone, uses remote electrical neuromodulation to activate the body’s natural ability to modulate pain.Researchers evaluated 45 patients aged 12 to 17 with a history of episodic and chronic migraines who completed at least one treatment with Nerivio. Over the course of the 12-week study, the device treated 159 migraine headaches, 49% of which were moderate and 33% of which were severe at baseline. Two hours after treatment, 71% of participants reported pain relief and 35% reported being free of pain, results that were sustained for 24 hours in 90% of cases. At two hours, 69% of patients experienced improved functional ability, which was defined as the ability to do schoolwork and perform “usual activities.” There were no device-related serious adverse events. ■“Remote Electrical Neuromodulation for Acute Treatment of Migraine in Adolescents” is posted here. ISSUES NewArchived

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance

Opioid-tolerant only (OTO) medications, such as transmucosal immediate-release fentanyl products and certain extended-release opioid analgesics, require prior opioid tolerance for safe use, as patients without tolerance may be at increased risk of overdose. Studies using insurance claims have found that many patients initiating these medications do not appear to be opioid tolerant. To measure prevalence of opioid tolerance in patients initiating OTO medications and to determine whether linked electronic health record (EHR) data contribute evidence of opioid tolerance not found in insurance claims data. This retrospective cohort study used a national database of deidentified longitudinal health information, including medical and pharmacy claims, insurance enrollment, and EHR data, from January 1, 2007, to December 31, 2016. Data included 131 756 US residents with at least 183 days of continuous enrollment in commercial or Medicare Advantage insurance (including medical and pharmacy benefits) who had received an OTO medication and who had no inpatient stays in the 30 days prior to starting an OTO medication; of these, 20 044 individuals had linked EHR data within the prior 183 days. Data were analyzed from July 1, 2017, to August 31, 2018. Initiating an OTO medication. Prior opioid tolerance demonstrated through pharmacy fills or EHR data on prescriptions written. Among 153 385 OTO use episodes identified, 89 029 (58.0%) occurred among women, 62 900 (41.0%) occurred among patients with Medicare Advantage insurance, 39 394 (25.7%) occurred in the Midwest, 17 366 (11.3%) occurred in the Northeast, 73 316 (47.8%) occurred in the South, and 23 309 (15.2%) occurred in the West. Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone. Among 20 044 OTO use episodes with linked EHR and claims data, less than 1% of OTO episodes identified in claims had evidence of opioid tolerance in structured EHR data that was not present in claims data (108 episodes [0.5%]). After limiting the sample to OTO episodes identified in claims with a matching OTO prescription within 14 days in the structured EHR data, only 40 of 939 episodes (4.0%) occurred among patients with evidence of tolerance that was not present in claims data. This cohort study found that most patients initiating OTO medications did not have evidence of prior opioid tolerance, suggesting they were at increased risk of opioid-related harms, including fatal overdose. Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing.

Study Finds REMS Program for Fentanyl Formulation Inadequate

Most prescriptions for transmucosal immediate-release fentanyl medications are written off label, a situation the FDA seeks to address by requiring more documentation and a patient registry.

Inappropriate use of transmucosal immediate-release fentanyl is common

Inappropriate use of transmucosal immediate-release fentanyl is common

Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing

Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P < .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P = .85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P = .01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P = .001). Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.

Assessment of the FDA Risk Evaluation and Mitigation Strategy for Transmucosal Immediate-Release Fentanyl Products

Transmucosal immediate-release fentanyls (TIRFs), indicated solely for breakthrough cancer pain in opioid-tolerant patients, are subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to prevent them from being prescribed inappropriately. To evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use; to describe sponsor assessments, based on claims data, of whether the REMS program was meeting its goals; and to characterize how the FDA responded to REMS assessments. Qualitative analysis of 4877 pages of FDA documents obtained through a Freedom of Information Act request, including 6 annual REMS assessment reports (2012-2017), FDA evaluations of these reports, and FDA-sponsor correspondence about safety issues. A REMS program to reduce the risk of adverse outcomes, including misuse, abuse, addiction, and overdose, arising from use of TIRFs. (1) Knowledge assessments of pharmacists, prescribers, and patients; (2) survey and claims-based prescribing assessments; (3) FDA and TIRF sponsor communications; (4) modifications to the REMS program; and (5) disenrollment of noncompliant prescribers. Twelve months after initiation of the program, 24 of 302 pharmacists (7.9%), 35 of 302 prescribers (11.6%), and 5 of 192 patients (2.6%) incorrectly reported that TIRFs can be prescribed to opioid-nontolerant patients, with similar levels of misunderstanding maintained in the subsequent reports. At 60 months, product-specific analyses of claims data indicated that between 34.6% and 55.4% of patients prescribed TIRFs were opioid-nontolerant. In the 48-month survey, 106 of 310 prescribers (34.2%) reported prescribing TIRFs for opioid-tolerant patients with chronic, noncancer pain; at 60 months, 54 of 302 prescribers (18.4%) and 148 of 310 patients (47.7%) erroneously reported that TIRFs were FDA-approved for such use. Over the 60-month period examined, there were few substantive changes made to the REMS to address evidence of high rates of off-label TIRF use, and, although the REMS program had a noncompliance plan, there was no report of prescribers being disenrolled for inappropriate prescribing. In this review of FDA documents pertaining to the TIRF REMS, surveys of pharmacists, prescribers, and patients reflected generally high levels of knowledge regarding proper TIRF prescribing, yet some survey items as well as claims-based analyses indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program.

Breakthrough cancer pain tailored treatment: which factors influence the medication choice? An observational, prospective and cross-sectional study in patients with terminal cancer

BackgroundVarious options for the pharmacological treatment of breakthrough cancer pain (BTcP) are available. International guidelines on BTcP treatment are not univocal. A tailored treatment should be based on the assessment...

Breakthrough Cancer Pain: A Systematic Review of Pharmacologic Management .

Breakthrough cancer pain (BtCP), defined as a transient exacerbation of pain that occurs in conjunction with well-controlled background pain, is a common and burdensome problem in patients with cancer. . The aim of this systematic review is to identify evidence-based pharmacologic modalities for adequate management of BtCP. . PubMed and CINAHL® databases were searched to identify literature regarding pharmacologic strategies for BtCP published from January 2006 to June 2016. These studies were then synthesized by the Oncology Nursing Society Putting Evidence Into Practice pain team. . Forty-four studies provide evidence for the use of opioids for the management of BtCP. Transmucosal immediate-release fentanyl (TIRF) was found to have the most evidence for BtCP. Five studies and guidelines also suggest that oral opioids (not including TIRF products) be dosed proportionally to baseline opioids at 10%-20% of the 24-hour, around-the-clock dose.

(459) Evaluation of liquid spray technology for sublingual drug delivery

Sublingual drug administration may be appropriate in multiple disease states, such as in patients who require rapid onset of effect (eg, transmucosal immediate-release fentanyl for breakthrough cancer pain [fentanyl sublingual spray]) or have conditions that negatively impact oral medication administration (eg, dysphagia, xerostomia), or when hepatic first-pass metabolism avoidance is desired. It is important for a sublingual spray device to accurately deliver microliter quantities of appropriate droplet size (eg, to prevent lung deposition) and have a simple, easy-to-use, durable mechanical design (eg, no springs). This study evaluated the characteristics of liquid spray technology for sublingual delivery. Two formulations (A and B) were evaluated and contained 30% v/v dehydrated alcohol, 5% v/v propylene glycol, 0.2% v/v peppermint oil, pH 9 borate buffer (quantity sufficient), and hydroxypropyl-beta-cyclodextrin (1:2); formulation B also contained 1% v/v hydroxypropyl cellulose (HPC-EP). Formulations were sprayed using a 0.1-mL multidose pump and evaluated for dose volume, spray pattern (methylene blue added; actuation 30 mm from target), and droplet size distribution using a Malvern Mastersizer particle size analyzer (n=25 spray samples). For formulations A and B, dose volumes were similar (mean volume, 100.4 and101.5 microliters, respectively; maximum single volume, 103.2 and 103.7 microliters). Spray patterns varied only slightly for formulations A versus B (small diameter mean [range], 50.6 millimeters [35.4-62.0] vs 34.0 millimeters [29-46.0], respectively; mean ratio largest/smallest diameter [range], 1.1 [1.0-1.3] vs 1.2 [1.1-1.5]). However, droplet size distribution varied with formulation A versus B (mean percentage share of droplet diameters at 10 micrometers [range], 1.7 [0.7-2.7] vs 0.7 [0.2-1.3], respectively). Overall, the characteristics of a liquid spray technology support further development for sublingual drug delivery. A formulation of fentanyl for sublingual administration is currently available, and research evaluating additional pain or addiction pharmacologic candidates for sublingual delivery in pain-related and other conditions is warranted. Supported by Insys Therapeutics. Sublingual drug administration may be appropriate in multiple disease states, such as in patients who require rapid onset of effect (eg, transmucosal immediate-release fentanyl for breakthrough cancer pain [fentanyl sublingual spray]) or have conditions that negatively impact oral medication administration (eg, dysphagia, xerostomia), or when hepatic first-pass metabolism avoidance is desired. It is important for a sublingual spray device to accurately deliver microliter quantities of appropriate droplet size (eg, to prevent lung deposition) and have a simple, easy-to-use, durable mechanical design (eg, no springs). This study evaluated the characteristics of liquid spray technology for sublingual delivery. Two formulations (A and B) were evaluated and contained 30% v/v dehydrated alcohol, 5% v/v propylene glycol, 0.2% v/v peppermint oil, pH 9 borate buffer (quantity sufficient), and hydroxypropyl-beta-cyclodextrin (1:2); formulation B also contained 1% v/v hydroxypropyl cellulose (HPC-EP). Formulations were sprayed using a 0.1-mL multidose pump and evaluated for dose volume, spray pattern (methylene blue added; actuation 30 mm from target), and droplet size distribution using a Malvern Mastersizer particle size analyzer (n=25 spray samples). For formulations A and B, dose volumes were similar (mean volume, 100.4 and101.5 microliters, respectively; maximum single volume, 103.2 and 103.7 microliters). Spray patterns varied only slightly for formulations A versus B (small diameter mean [range], 50.6 millimeters [35.4-62.0] vs 34.0 millimeters [29-46.0], respectively; mean ratio largest/smallest diameter [range], 1.1 [1.0-1.3] vs 1.2 [1.1-1.5]). However, droplet size distribution varied with formulation A versus B (mean percentage share of droplet diameters at 10 micrometers [range], 1.7 [0.7-2.7] vs 0.7 [0.2-1.3], respectively). Overall, the characteristics of a liquid spray technology support further development for sublingual drug delivery. A formulation of fentanyl for sublingual administration is currently available, and research evaluating additional pain or addiction pharmacologic candidates for sublingual delivery in pain-related and other conditions is warranted. Supported by Insys Therapeutics.

Integrated Palliative Care for Management of Elderly Patients with Advanced Chronic Kidney Disease (FR433)

Accreditation System (NAS), the ACGME is increasingly emphasizing the teaching of patient safety and QI in training programs. It is critical that palliative care practitioners of all disciplines have an understanding of QI processes and the ability to implement these processes in the clinical setting. Using a multiinstitutional, interdisciplinary team of quality experts and education leaders in palliative care, we aim to demonstrate how audience members can incorporate novel teaching methods into QI for their own learners. We will introduce a tool for reporting and assessing QI projects. Then, using this tool, we will review three examples of QI projects from several institutions in a small-group format, inviting open conversation regarding their strengths, weaknesses, and applicability. This will spur lively discussions on the challenges and barriers of QI initiatives within our field or those that integrate with other disciplines. Lastly, we will review successful methods from our own experience of integrating QI into the longitudinal curriculum of our palliative care fellowships and interdisciplinary teams, such as risk evaluation and mitigation strategies (REMS) for buprenorphine, extendedrelease and long-acting opioid analgesics, and transmucosal immediate-release fentanyl products; institutional risk reporting systems; and patient safety committees. Overall, we aim to provide audience members with an implementable action plan to take home that inspires lifelong QI.

フェンタニル口腔粘膜吸収剤の使用実態調査

フェンタニル口腔粘膜吸収剤の使用実態調査

Medication Safety

Medication Safety

A review of rapid-onset opioids for breakthrough pain in patients with cancer.

Pain management in patients with cancer remains suboptimal. Breakthrough pain (BTP) is characterized by abrupt onset of severe pain in a background of otherwise stable managed pain and presents a substantial burden to patients, as it disrupts activities and quality of life. Rapid-onset opioids (ROOs), with an appropriate onset and duration of effect, provide new options for effective and well-tolerated management of BTP. All currently available ROOs are various formulations of transmucosal immediate-release fentanyl (TIRF) and, although they were originally developed and approved for use in children before painful procedures, are only approved for use in opioid-tolerant adult patients with cancer and BTP. The formulation options include oral lozenge, buccal tablet, buccal film, sublingual tablet, nasal spray, and a sublingual spray; each has practical considerations that vary with the product and route of administration. All have the common advantage of rapid entry into the systemic circulation via transmucosal absorption, avoiding hepatic and intestinal first-pass metabolism and allowing a rapid onset of action that rivals intravenous injections. Rapid onset and short duration of action allow good patient control of analgesia. The pharmacokinetic and analgesic properties of ROOs may allow reduction of the total opioid burden and associated adverse effects, while still providing effective pain relief. The shared TIRF risk evaluation and mitigation strategy program implemented in March 2012 has simplified enrollment and administration of these products to help mitigate the risks of abuse and misuse and to help ensure safe use in patients with cancer suffering from BTP.

California provider status bill heads to governor

California provider status bill heads to governor

Development of a federally mandated risk evaluation and mitigation strategy (REMS) for transmucosal immediate-release fentanyl products

Opioid analgesics, including transmucosal immediate-release fentanyl (TIRF) products, are associated with serious risks of abuse, addiction, and overdose. In 2007, Congress passed the Food and Drug Administration Amendments Act (FDAAA), requiring manufacturers to implement a Risk Evaluation and Mitigation Strategy (REMS) for opioid distribution. In 2009, recommendations for “Elements to Assure Safe Use” (ETASU) were released. In March 2012, a shared TIRF-REMS program (http://www.tirfremsaccess.com) was implemented; the shared TIRF-REMS was modeled in part on a separate REMS program for sublingual TIRF tablets. The goals of the shared TIRF-REMS program are to “mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors.” These goals were designed to limit dispensing to appropriate patients, prevent inappropriate conversion between fentanyl products, avoid accidental exposure, and educate about risks. The shared TIRF-REMS program is controlled by a limited-access distribution system that mandates enrollment and certification of prescribers, pharmacies, distributors, and patients. Clinicians who prescribe TIRF products to outpatients must meet several ETASU requirements, including reviewing educational materials and completing a Prescriber Knowledge Assessment (https://www.tirfremsaccess.com/TirfUI/rems/education.action) and Prescriber Enrollment Form (https://www.tirfremsaccess.com/TirfUI/rems/pdf/prescriber-enrollment-form.pdf). A Patient-Prescriber Agreement Form (https://www.tirfremsaccess.com/TirfUI/rems/pdf/ppaf-form.pdf) must be submitted within 10 days from prescription processing; only 3 prescriptions can be written until the form is received. Form renewals are required every 2 years. Pharmacies distributing TIRF products must meet specific guidelines, including designating a pharmacist to be responsible for a pharmacy management system that supports communication with the TIRF-REMS program; however, pharmacies dispensing TIRF products solely to inpatients only need to be certified. Although the shared TIRF-REMS program is an important step toward the FDAAA goals, it is likely that additional measures will be needed, including procedures to control non-prescription opioid misuse and abuse. Supported by ProStrakan. Opioid analgesics, including transmucosal immediate-release fentanyl (TIRF) products, are associated with serious risks of abuse, addiction, and overdose. In 2007, Congress passed the Food and Drug Administration Amendments Act (FDAAA), requiring manufacturers to implement a Risk Evaluation and Mitigation Strategy (REMS) for opioid distribution. In 2009, recommendations for “Elements to Assure Safe Use” (ETASU) were released. In March 2012, a shared TIRF-REMS program (http://www.tirfremsaccess.com) was implemented; the shared TIRF-REMS was modeled in part on a separate REMS program for sublingual TIRF tablets. The goals of the shared TIRF-REMS program are to “mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors.” These goals were designed to limit dispensing to appropriate patients, prevent inappropriate conversion between fentanyl products, avoid accidental exposure, and educate about risks. The shared TIRF-REMS program is controlled by a limited-access distribution system that mandates enrollment and certification of prescribers, pharmacies, distributors, and patients. Clinicians who prescribe TIRF products to outpatients must meet several ETASU requirements, including reviewing educational materials and completing a Prescriber Knowledge Assessment (https://www.tirfremsaccess.com/TirfUI/rems/education.action) and Prescriber Enrollment Form (https://www.tirfremsaccess.com/TirfUI/rems/pdf/prescriber-enrollment-form.pdf). A Patient-Prescriber Agreement Form (https://www.tirfremsaccess.com/TirfUI/rems/pdf/ppaf-form.pdf) must be submitted within 10 days from prescription processing; only 3 prescriptions can be written until the form is received. Form renewals are required every 2 years. Pharmacies distributing TIRF products must meet specific guidelines, including designating a pharmacist to be responsible for a pharmacy management system that supports communication with the TIRF-REMS program; however, pharmacies dispensing TIRF products solely to inpatients only need to be certified. Although the shared TIRF-REMS program is an important step toward the FDAAA goals, it is likely that additional measures will be needed, including procedures to control non-prescription opioid misuse and abuse. Supported by ProStrakan.

Grading clinical guidelines for the use of transmucosal immediate-release fentanyl products in breakthrough pain

Pain is a complex symptom that is commonly feared in palliative care owing to its significant effects on patients' quality of life (QoL), and is directly associated with morbidity. More specifically, the management of breakthrough pain (BTP) is particularly important. Opioids play a major part in the management of BTP, and the various transmucosal immediate-release fentanyl (TIRF) products are a common treatment choice. This paper considers the strength of the evidence underlying recommendations regarding the use of TIRF. Failure to consider the quality of evidence in practice can lead to misguided recommendations. Guidelines should therefore be used to inform clinicians of the quality of the underlying evidence and whether recommendations are strong or weak. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach is increasingly being adopted worldwide as it provides a system for rating quality of evidence and strength of recommendations that is clear, comprehensive, transparent, and practical. This paper adopts the GRADE approach to assess the strength of recommendations made in a 2011 review by Zeppetella in order to develop guidelines for the use of TIRF. The recommendations include that TIRF products can be considered for first-line treatment and that they should be individualised to patients who are on a background opioid.

Toxicology Fellow’s Perspective: Filling a Void in Medical Education Regarding Opioids

Toxicology Fellow’s Perspective: Filling a Void in Medical Education Regarding Opioids

Opioids, pain management and the law

Approximately 100 million people suffer from chronic pain in the USA. Opioid medications are commonly prescribed to treat pain, but are becoming the most widely misused controlled substance nationally. Physicians who treat patients with chronic pain must be cognizant of the federal and state policies that govern the distribution of opioid medications as well as the current standards of medical practice for opioid prescribing. The laws and policies regarding the standard medical practice for opioid prescribing are constantly subject to revision. The National Drug Control Policy announced its plan to fight prescription drug abuse in 2011 and unveiled the Risk Evaluation and Management Strategy initiative. Currently there is a Risk Evaluation and Management Strategy for Transmucosal Immediate-Release Fentanyl. Other resources, such as state-run prescription drug monitoring programs, are also available to many physicians. The level of participation in these programs by physicians and pharmacists varies by state, and funding for continuation of these programs is an ongoing issue. The problems of undertreated pain and the epidemic of prescription drug abuse have coincided, creating a need for medical and social policy that protects society and access to appropriate care for those in pain. Federal and state laws are in evolution, and clinicians must remain aware of these changes as well as the issues behind them that will impact safe and appropriate care of patients in pain.

Shared Risk Evaluation Mitigation Strategy for all Immediate-Release Transmucosal Fentanyl Dosage Forms

EDITOR'S ABSTRACTThe Food and Drug Administration approved a single shared Risk Evaluation Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl dosage forms in December 2011. This report describes the goals, elements, and restricted distribution system of the REMS designed to reduce risk of abuse, misuse, addiction, and overdose with the drugs. Questions and answers about REMS also are presented.The U.S. Food and Drug Administration (FDA) announced a shared REMS for all immediate-release transmucosal fentanyl dosage forms on December 29, 2011, to become effective in March 2012. That announcement is accessible at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm285345.htm. Concurrently the FDA posted a series of questions and answers on this shared REMS at: http://http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm284717.htm. Both documents are in the public domain.