Risk Management Advisory Committee Research Articles

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Back to table of contents Previous article Next article Clinical and Research NewsFull AccessMed CheckNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:3 Aug 2018https://doi.org/10.1176/appi.pn.2018.8a3FDA Panel Rejects Abuse-Deterrent Oxycodone FormulationParticipants in a joint meeting of the Food and Drug Administration’s Anesthetic and Analgesic Drug Products Advisory Committee and its Drug Safety and Risk Management Advisory Committee in June voted 14-3 not to recommend the approval of Remoxy ER (oxydone extended-release capsules) for the management of severe pain. Remoxy ER, made by Pain Therapeutics Inc., is a high-viscosity gel formulation designed to keep people from being able to cut, grate, or inject the drug. Some committee members suggested that data presented on the efficacy, safety, and risk-benefit profile of Remoxy ER did not support approval of its application, especially regarding claims of abuse deterrence.Sage Announces Expedited Development Plan for Depression MedicationSage Therapeutics in June announced its expedited development plan for its lead compound SAGE-217 following a meeting with the FDA. SAGE-217, a drug that targets the GABA-A receptor, received FDA breakthrough status in February for the treatment of major depressive disorder (MDD).The new plan includes expedited approval pathways for SAGE-217 for both MDD and postpartum depression (PPD). An ongoing phase 2 study comparing depressive symptoms in women with PPD who receive either 30 mg SAGE-217 or placebo for two weeks was confirmed as appropriate to support registration for PPD, the company noted. The FDA also requested n additional phase 3 trial for MDD. The trial will compare outcomes in 450 patients who take SAGE-217 (20 mg or 30 mg) or placebo for two weeks. Sage will also begin a one-year open-label study of patients with major depression to acquire additional safety data and evaluate the long-term effectiveness of two weeks of SAGE-217 for recurrent major depressive episodes. Saladax Signs Agreement to License Blood Tests For Antipsychotic LevelsIn June, the diagnostics company Saladax Biomedical Inc. signed a license agreement with Janssen Pharmaceutical NV—one of the Janssen Pharmaceutical companies—to acquire exclusive patent rights for diagnostic blood tests that can determine drug levels in patients undergoing treatment with antipsychotic medications. “This intellectual property, along with the existing patents that Saladax already owns, places Saladax in a predominant position in the field of antipsychotic drug testing,” according to a press release by the company. Saladax in March received approval to sell two of its diagnostic tests on the European market: the MyCare Total Risperidone Assay Kit and MyCare Paliperidone Assay Kit. The company has four additional tests for aripiprazole, clozapine, olanzapine, and quetiapine that it expects will receive European clearance later this year. Saladax stated the company will soon seek FDA clearance for these tests as well. Guidelines Released For Use of Ketamine to Treat Acute PainThe American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and American Society of Anesthesiologists recently joined together to develop consensus guidelines on the use of intravenous ketamine to treat both chronic and acute pain.These guidelines, published in the journal Regional Anesthesia and Pain Medicine in June, cover a range of scenarios, but broadly state that moderate evidence supports the use of ketamine for acute pain management following painful surgeries, including in people who are opioid dependent. There is also moderate evidence that ketamine works for chronic spinal pain and complex regional pain syndrome. There is limited evidence to support ketamine for other types of chronic or acute pain. The guidelines noted that ketamine should be avoided in people with poorly controlled cardiovascular disease, those with active psychosis, and pregnant women. ■Schwenk, ES et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):456-466. ISSUES NewArchived

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Back to table of contents Previous article Next article Med CheckFull AccessMed CheckNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:15 Dec 2017https://doi.org/10.1176/appi.pn.2017.12b53FDA Fast Tracks Alzheimer’s MedicationAlzheon Inc.’s oral anti-amyloid medication ALZ-801, a prodrug formulation of the compound tramiprosate, has been granted fast-track status by the Food and Drug Administration (FDA).Tramiprosate—which was designed to break down amyloid aggregates—failed in a previous clinical trial, but investigators found data to suggest the prodrug version could work in patients with the APOE4 risk gene. Alzheon is initiating a new phase 3 study of ALZ-801 that will specifically enroll participants who are homozygous for the risk gene and have a diagnosis of mild Alzheimer’s.FDA Committees Recommend Approval of Buprenorphine InjectableThe FDA Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee jointly voted 17-3 in favor of approving of CAM2038, a buprenorphine injection for the treatment of adults with opioid use disorder (OUD).CAM2038, developed by Braeburn Pharmaceuticals, is available in both weekly and monthly formulations. The drug is intended to be administered by health care professionals to ensure proper delivery of medication, while also minimizing risks of diversion, misuse, and accidental pediatric exposure.The committee’s recommendation was based on the results of seven clinical trials, including a phase 3 efficacy study and a long-term safety study. CAM2038 was given a priority review designation by the FDA in September.FDA Approves Implant For Sleep ApneaThe FDA in October approved an implantable neurostimulation device to treat moderate-to-severe central sleep apnea. Central sleep apnea occurs when the brain fails to send signals to the diaphragm to breathe. The resulting loss of sleep quality can lead to a range of physical and behavioral complications. The device, called the Remedē System, is an implanted nerve stimulator that sends electrical currents to the phrenic nerve to stimulate the diaphragm and restore normal breathing. The Remedē System, manufactured by Respicardia, is implanted under the skin of the upper chest. The approval was based on a clinical trial of 141 patients. After six months, more than half of the patients implanted with the active Remedē System saw at least a 50 percent reduction in their apnea hypopnea index, which measures the severity and frequency of sleep apnea, compared with only 11 percent of patients in the control group.Alkermes Submits NDA For Long-Acting Injectable InitiatorAlkermes has submitted a New Drug Application to the FDA for its novel injectable compound Aripiprazole Lauroxil NanoCrystal Dispersion. The product was designed to provide extended-release aripiprazole in a formulation that enables faster dissolution and leads to more rapid achievement of therapeutic levels of aripiprazole.If approved, administration of this product in conjunction with a single oral dose of 30 mg aripiprazole could replace the need for three weeks of concominant oral aripiprazole following the first injection of the extended-release formulation of aripiprazole, according to the company.“Patients with schizophrenia are particularly vulnerable to nonadherence and relapse when transitioning from inpatient care to outpatient settings,” said Alkermes’ Executive Vice President of Research and Development Elliot Ehrich, M.D., in a press release. “The ability to initiate long-acting treatment with Aristada on Day 1 without the need to continue oral supplementation during this critical transition period may be a useful and welcomed option for the clinical community.” ■ ISSUES NewArchived

FDA and the safe and appropriate antibiotic use of fluoroquinolones

The thorny topic of fluoroquinolone use in so-called trivial infections was reviewed in respect of risks and benefits on Nov 4, 2015, when a joint meeting of two US Food and Drug Administration (FDA) advisory committees (antimicrobial drugs and drug safety) was convened to discuss the relative risks and benefits in three infections: acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and uncomplicated urinary tract infections. 1 US Food and Drug AdministrationJoint Meeting of the Antimicrobial Drugs Advisory Committee Meeting (AMDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm470444.pdfDate: 2015 Google Scholar

Advisors Call for No New Heart Warnings for NSAIDs

SILVER SPRING, MD – No major change is needed to the warning labels on prescription and over-the-counter nonsteroidal anti-inflammatory medications, according to two panels of Food and Drug Administration advisers. The members of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee said that the evidence about potentially new cardiovascular (CV) risks, which may target arthritis patients with drugs in the class, was not sufficient to change labeling. And they said there were not enough data to suggest that naproxen presented a substantially lower risk of CV events than did either ibuprofen or selective NSAIDs, such as cyclooxygenase-2 inhibitors. But some panelists said that even without a label change, the evidence on naproxen – which showed a trend toward a better safety profile – would probably sway them to prescribe or recommend it more often, especially in patients at risk for CV side effects. However, there was concern for patients with rheumatic diseases, who are considered to be at higher risk for CV events. Robert Lahita, MD, PhD, an arthritis committee member and a professor of medicine at Rutgers Biomedical and Health Sciences, Newark, NJ, said that his rheumatoid patients “take NSAIDs like candy.” Irwin J. Russell, MD, PhD, a fibromyalgia researcher at the Arthritis and Osteoporosis Center of South Texas, San Antonio, said that the data on NSAIDs should prompt inquiries into whether the elevated cardiovascular disease risk in rheumatic patients might be linked to their chronic use of the medications. In June 2005, the FDA required all prescription NSAIDs to have a boxed warning on the potential for serious adverse CV events. NSAIDs also carry a warning on the potential for gastrointestinal adverse events. A Medication Guide was developed for patients to inform them of the risk of CV events and gastrointestinal bleeding with all NSAIDs. PA/LTC PerspectiveUniversity of Maryland School of Nursing Professor Barbara Resnick, PhD, CRNP, FAAN, FAANP, said that several issues regarding NSAIDs raise concerns in the PA/LTC population.“For some individuals, NSAIDs provide extraordinary pain relief and truly optimize quality of life. For others, these medications make little difference, and the pain they experience may be better managed by behavioral interventions and other treatment options. Thus, use of NSAIDs, including naproxen, should be individualized and considered as a short-term option for pain relief.” University of Maryland School of Nursing Professor Barbara Resnick, PhD, CRNP, FAAN, FAANP, said that several issues regarding NSAIDs raise concerns in the PA/LTC population. “For some individuals, NSAIDs provide extraordinary pain relief and truly optimize quality of life. For others, these medications make little difference, and the pain they experience may be better managed by behavioral interventions and other treatment options. Thus, use of NSAIDs, including naproxen, should be individualized and considered as a short-term option for pain relief.” The latest panel meeting was held because “9 years later, there are more data available and questions still remain,” said John Jenkins, MD, director of the FDA's Center for Drug Evaluation and Research. The committee did say that it would like to see clearer warnings on over-the-counter NSAIDs, especially emphasizing that patients should take the lowest possible dose for the shortest period of time. In briefing documents that were issued ahead of the joint meeting, the FDA said that naproxen may carry a lower risk of CV thromboembolic events than that of other selective or nonselective NSAIDs. According to the documents, the primary evidence for a better CV safety profile for naproxen comes from a meta-analysis conducted by the Coxib and traditional NSAID Trialists’ (CNT) Collaboration at Oxford University (Lancet 2013;382[9894]:769–79). The Oxford meta-analysis brings into question whether Pfizer should continue its long-term study comparing the safety of naproxen, ibuprofen, and celecoxib, which was begun in the wake of the 2005 events and at the agency's behest.

FDA Officially Calls for Schedule Hike for Hydrocodone Products

FDA Officially Calls for Schedule Hike for Hydrocodone Products

FDA recommends reclassifying hydrocodone to Schedule II

& Human Services (HHS) Secretary Kathleen Sebelius by early December. FDA anticipates that the National Institute on Drug Abuse will agree with the recommendation. HHS will then submit its recommendation to DEA, which will make the fi nal decision on appropriate scheduling of these products. “FDA has been challenged with determining how to balance the need to ensure continued access to those patients who rely on continuous pain relief while addressing the ongoing concerns about abuse and misuse,” the agency wrote in an October 24 statement by Janet Woodcock, MD, Director of FDA’s Center for Drug Evaluation and Research. “This determination comes after a thorough and careful analysis of extensive scientifi c literature, review of hundreds of public comments on the issue and several public meetings, during which we received input from a wide range of stakeholders, including patients, health care providers, outside experts, and other government entities.” History of a complex issue In recent years, the issue has gathered momentum as deaths from overdoses of opioid pain relievers have surpassed deaths from overdoses of cocaine and heroin combined, according to CDC data. New York State became the fi rst (and to date, only) state to reschedule hydrocodone in a law that became effective February 23, 2013; the hydrocodone part of the law contains several patient access waivers. In addition, similar state efforts include no refi lls in Oklahoma and dispensing no more than a 30-day supply in Tennessee, according to the National Alliance of State Pharmacy Associations. On a federal level, recent activity in Congress included the introduction of hydrocodone rescheduling legislation on March 20, 2013 (additional attempts to reschedule legislatively are possible if lawmakers think DEA isn’t moving quickly enough). On the regulatory side, in 2009, DEA asked HHS for a recommendation on upscheduling hydrocodone combination products. On January 25, 2013, FDA’s Drug Safety and Risk Management Advisory Committee voted 19–10 in favor of reclassifying hydrocodone to Schedule II. Five of the 29 voting members on that advisory committee have pharmacy degrees, according to public materials on the FDA website; analyzing the vote, 4 of the pharmacists voted in favor of reclassifi cation and 1 voted against. The new statement from Woodcock explained that FDA was announcing its intent because of “the unique history of this issue and the tremendous amount of public interest.” (See page 48 for information on FDA’s new approval of Zohydro.) APhA opposes rescheduling APhA was joined by other national pharmacy groups in opposing rescheduling of hydrocodone combination products in a November 11 letter to Sebelius. In addition to APhA, pharmacy organizations cosigning the letter included the Academy of Managed Care Pharmacy, American Society of Consultant Pharmacists, National Alliance of State Pharmacy Associations, National Association of Chain Drug Stores, and National Community Pharmacists Association. “While we appreciate the efforts of the FDA to address the serious issue of prescription drug abuse, we believe rescheduling hydrocodone is not the solution,” APhA and the other groups wrote. “Rescheduling will have a profoundly negative impact on patients who legitimately need these medications and a negligible impact on drug abuse.” According to the November 11 joint letter, rescheduling hydrocodone would create serious barriers to patient access such as the inability to refi ll products in Schedule II; new burdens for an already overtaxed health care system; and new requirements for pharmacies, including the provision of additional secure storage, recordkeeping, and inventory management. In contrast, the American Society of Health-System Pharmacists (ASHP) sent a November 5 letter to the HHS Secretary supporting hydrocodone rescheduling. “ASHP called concerns regarding recordkeeping and security processes resulting from rescheduling ‘valid,’ but believes that they are outweighed by the public health benefi t arising from increased control of drugs with high abuse potential,” according to a related ASHP news release. ASHP “also countered concerns that the inability to prescribe refi lls would have a broad impact on patient access.” hydrocodone

The Downside of Upscheduling

Intercontinental Marketing Services (IMS) data estimate 130 million hydrocodone prescriptions were written in 2006, up approximately 50% from 88 million in 2000 [1]. This greater availability is thought to have contributed, at least in part, to hydrocodone's illicit use. In 2012, hydrocodone ranked 1st on the RADARS poison center list and the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System college survey list [2]. The January 2012 Drug Abuse Warning Network (DAWN) report showed, among pain reliever-related emergency department (ED) visits involving drug misuse or abuse by adolescents, oxycodone and hydrocodone were the most commonly involved opioids [3]. On March 20, 2012, legislation was proposed to reschedule hydrocodone products and the Food and Drug Administration (FDA) Drug Safety and Risk Management Advisory Committee voted “yes”, recommending rescheduling of hydrocodone from Schedule 3 to Schedule …

Hydrocodone shift to Schedule II considered

Sens. Joe Manchin (D-WV) and Mark Kirk (R-IL) and Reps. Vern Buchanan (R-FL) and Ed Markey (D-MA) introduced hydrocodone rescheduling legislation on March 20. The Safe Prescribing Act of 2013 (S. 621) would reclassify hydrocodone products such as Vicodin and Lortab from a Schedule III to a Schedule II controlled substance. "Under the new restrictions, a written prescription would be required in order to receive hydrocodone painkillers except in cases of emergency," according to Manchin's news release. "Pharmacists would require patients to present an original prescription for refills, and traffickers would be subject to harsher fines and penalties."■Hydrocodone rescheduling is being considered by Congress, FDA, and DEA.■New York State has experience with hydrodone rescheduling. ■Hydrocodone rescheduling is being considered by Congress, FDA, and DEA.■New York State has experience with hydrodone rescheduling. As the proposed hydrocodone legislation moves through Congress—by April 24, the Senate bill had drawn 7 cosponsors and the House bill (H.R. 1285) had attracted 50 cosponsors— the same idea is under consideration by federal regulatory authorities. Among the states, New York was the first to move hydrocodone to Schedule II. "We will not be the only one," Craig M. Burridge, MS, CAE, former Executive Director of the Pharmacists Society of the State of New York, told Pharmacy Today. FDA's Drug Safety and Risk Management Advisory Committee voted 19–10 on January 25 to recommend rescheduling of hydrocodone from Schedule III to Schedule II. FDA will now consider its advisory committee's recommendation in a final recommendation to DEA. Then DEA would have to go through a rulemaking process to propose rescheduling. Steve Simenson, BSPharm, FAPhA, DPNAP, now APhA President, and Marcie Bough, PharmD, former APhA Senior Director of Government Affairs, testified on January 24 of the 2-day advisory committee hearing. APhA did not take a position, but rather provided information, including on the change's impact on patient access. Bough told Today that "going through the regulatory process is the appropriate venue to consider rescheduling and allows more time for stakeholder input." Following the vote, 18 groups— including the American Society of Consultant Pharmacists, National Association of Chain Drug Stores, and National Community Pharmacists Association—signed a February 1 letter urging FDA to reject hydrocodone rescheduling. "No evidence currently exists to show that reclassifying hydrocodone will curb misuse and abuse of pain medications," these groups wrote. "In contrast, there is evidence that rescheduling medications to higher classifications can reduce patient access to medications and cause harm." But Manchin stated in his news release that "the heart-wrenching stories I hear from so many West Virginians underscore the serious need to immediately reschedule hydrocodone." Last year, as Congress was considering Prescription Drug User Fee Act reauthorization legislation, Manchin introduced an amendment with language on hydrocodone rescheduling that passed the Senate on May 24, 2012. The House version did not include the language. APhA opposed that language in the context of the congressional amendment process, signing onto May 30, 2012, letters from pharmacy groups to House and Senate offices. In New York State, hydrocodone was rescheduled as part of the Internet System for Tracking Over Prescribing (iSTOP) law that was signed by the governor on August 27, 2012. The hydrocodone part of the law includes several patient access waivers and became effective February 23, 2013. The shift to Schedule II has been "mostly smooth for those pharmacists who were given a heads up of the changes so that they could inform their patients and prescribers," Burridge said. At community pharmacies, there was "initial yelling at the counter," he added. "I think people are more aware now, and if they truly do have chronic pain, this will be resolved with their physician." The state pharmacists society neither supported nor opposed hydrocodone rescheduling. "There seemed to be a 50–50 split even among our own members and our own board," Burridge said. But the state society was concerned about the entire iSTOP bill when it emerged from the attorney general's office because it was "all about punishment … and it had nothing to do with protecting patient access." So the state society developed a task force bringing stakeholders—including state legislators, the attorney general's counsels, the medical society, dentists, and hospice—around a table in its boardroom. One of the first things the task force did was to get the state to put $46 million in the budget to open up more rehab slots for people with addictions. "The task force totally changed the bill from where it was," Burridge said. "With the waivers and exceptions, we think we took care of most of the issues that would arise from patient access."

Experts recommend against calcitonin-salmon for postmenopausal osteoporosis

The benefits of calcitonin-salmon for the treatment of postmenopausal osteoporosis are minimal and do not outweigh an uncertain cancer risk associated with the drug, a slim majority of FDA advisers concluded March 5. The 12–9 vote by members of FDA’s Drug Safety and Risk Management Advisory Committee and the Advisory Committee for Reproductive Health Drugs was in line with a decision reached last July by European regulators. In Europe, because of the possible cancer risk, calcitonin-containing products may be used only as short-term treatment for hypercalcemia or for the prevention of acute bone loss due to sudden immobilization or Paget’s disease. Data suggesting calcitonin may cause cancer came from clinical trials of an investigational oral formulation of the drug being developed by Denmark-based Nordic Bioscience for the treatment of osteoarthritis. In those studies, a possible link between calcitonin use and prostate cancer was noted by a safety monitoring committee. After examining the study data, FDA stated that the initial risk of prostate cancer appeared equal among calcitonin-treated patients and placebo recipients, and the perceived safety signal was “not of great concern.”

FDA advisory committee recommends hydrocodone rescheduling

FDA’s Drug Safety and Risk Management Advisory Committee has voted to recommend rescheduling of hydrocodone from Schedule III (C-III) to Schedule II (C-II). The January 25 vote was 19–10 in favor of the change. FDA’s Drug Safety and Risk Management Advisory Committee has voted to recommend rescheduling of hydrocodone from Schedule III (C-III) to Schedule II (C-II). The January 25 vote was 19–10 in favor of the change. The next steps are that FDA will consider its advisory committee’s recommendation as the agency determines its final recommendation to DEA. Then DEA would have to go through a rulemaking process to propose rescheduling “if it goes that far,” explained APhA Senior Director of Government Affairs Marcie Bough, PharmD.■ At an FDA advisory committee meeting on rescheduling hydrocodone, APhA and other groups discussed other ways of addressing prescription drug abuse and patient safety.■APhA’s testimony provided information on pharmacy logistics and operations and the impact on patient access. ■ At an FDA advisory committee meeting on rescheduling hydrocodone, APhA and other groups discussed other ways of addressing prescription drug abuse and patient safety.■APhA’s testimony provided information on pharmacy logistics and operations and the impact on patient access. Bough and APhA President-elect Steve Simenson, BSPharm, FAPhA, DPNAP, testified on January 24 of the 2-day hearing of the advisory committee. APhA did not take a position, but rather provided information on pharmacist and pharmacy issues—including impact on patient access—for committee members to consider as they decided their votes. “APhA will continue to monitor the activities and engage when appropriate, as it moves through the regulatory process,” Bough said. Bough drew a distinction between FDA holding the advisory committee meeting and Congress considering an amendment, with language on hydrocodone rescheduling, on last year’s Prescription Drug User Fee Act reauthorization legislation; APhA had joined May 30 letters to Senate and House offices signed by pharmacy groups opposing the amendment. “In general, the congressional amendment process is not the venue to consider rescheduling a product,” she said. “Going through the regulatory process is the appropriate venue to consider rescheduling and allows more time for stakeholder input.” All hydrocodone products on the market are combination products, Bough said. FDA’s briefing materials indicated that in 2011, there were approximately 131 million prescriptions, and 47 million patients received hydrocodone-containing products. Given the number of prescription orders, APhA highlighted the impact on patient access due to the differences in pharmacy operations and logistics if that many prescriptions shifted from C-III procedures to C-II, she noted. Under a reclassification, there would be no refills, the patient would need to obtain a new prescription, and the entire pharmacy supply chain and pharmacy operations would be affected. Pharmacy impact points would include extra steps in the administrative process and time to process prescription orders that then translates to an impact on patient care and access to pain management, including the capacity of medicine to accommodate more monthly office visits for new C-II prescriptions, the capacity of pharmacy to manage more new monthly C-II prescriptions, the lack of C-II prescription refills and no C-II fax refill reminders and requests to medical offices, and the very limited use of a DEA regulation allowing a 90-day supply of C-IIs via postdated prescription orders. There are additional considerations for long-term care and assisted living practice settings. In fact, rescheduling affects the various pharmacy practice settings in different ways. In testimony, APhA also discussed important areas of evolving work related to other efforts to address prescription drug abuse and patient safety, such as prescription drug monitoring programs (PDMPs) and e-prescribing of controlled substances, state-specific C-II laws, the pharmacist’s role in patient care activities and in working with medicine to improve management of pain patients, and the example of Simenson’s practice in Minnesota, in which pharmacists work up patients, review the PDMP, provide the information to the physician, and work together through a collaborative practice agreement. APhA additionally supported efforts to improve medication disposal. On January 25, testimony by the National Community Pharmacists Association (NCPA) and the National Association of Chain Drug Stores (NACDS) raised concerns about patient access and pharmacy operations, expressed opposition to rescheduling, and discussed other efforts to address prescription drug abuse and diversion. NCPA and NACDS were 2 of the 18 organizations to sign a February 1 letter to FDA Commissioner Margaret A. Hamburg, MD, that shared concerns about the January 25 vote. “No evidence currently exists to show that reclassifying hydrocodone will curb misuse and abuse of pain medications,” the groups wrote. “In contrast, there is evidence that rescheduling medications to higher classifications can reduce patient access to medications and cause harm.”

Look, Over Here, Some Real LTC-Policy News

Look, Over Here, Some Real LTC-Policy News

The Drug Safety and Risk Management Advisory Committee

The Food and Drug Administration Amendments Act (FDAAA) of 2007 granted FDA-expanded drug safety authority. We hypothesized that meetings involving the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee might serve as a barometer for the impact of FDAAA on drug safety regulatory decision making. We conducted a case study analysis of 42 DSaRM advisory committee meetings held between 2002 and 2011. Publicly available sources (FDA meeting minutes and materials, safety alerts, and drug manufacturer Web sites) were reviewed to describe and compare DSaRM meeting frequency, content and outcomes between the pre-FDAAA (2002-2007) and post-FDAAA (2008-2011) periods. DSaRM meeting frequency increased after FDAAA (from 2.7 to 6.5 meetings per year). DSaRM meetings were more likely to be held jointly with other drug advisory committees after FDAAA (from 68% to 92% of meetings). DSaRM members were invited participants in 35 additional meetings of other drug advisory committees (2007-2011). DSaRM meetings were more likely to review issues of approvability (eg, new drugs, new indications, and new product formulations) after FDAAA. FDA questions to the committee were more likely to request an explicit drug safety assessment after FDAAA (from 31% to 76% of meetings). Content analysis of meeting outcomes and subsequent FDA regulatory decisions did not suggest a more or less risk aversive climate after FDAAA. Increased DSaRM advisory committee activity indicates its advice was being sought more broadly for drug regulatory decision making and at earlier stages of drug development after FDAAA was enacted.

Health care reform: Pharmacy's opportunity to move forward

Health care reform: Pharmacy's opportunity to move forward

New Study Answers Questions About Cardiac Risk of ADHD Drugs

New Study Answers Questions About Cardiac Risk of ADHD Drugs

With REMS, what goes up can come down

Recent actions by FDA indicate the agency, when shown evidence that a suspected risk does not really exist, will alter a risk evaluation and mitigation strategy (REMS). In the past half year, the agency has lifted a requirement for monthly liver-function tests for one drug and, for another drug, eliminated the REMS program altogether. “I’m not surprised,” said Timothy Lesar, pharmacy director at Albany Medical Center in New York. Having participated in and witnessed numerous meetings of FDA’s advisory committees, Lesar said discussants regularly express concern about “rare, serious” adverse events that occurred in clinical trials of drugs for rare diseases. “People are going to wonder: [The company] only studied 200 patients . . . and 2 of them had anaphylactic reactions,” the former member of FDA’s Drug Safety and Risk Management Advisory Committee said. “But, you’re not sure if that’s a drug effect. “You just sort of . . . say, ‘Well, gee, you could collect data on this.’

Insulin Sensitizers and Heart Failure: An Engine Flooded with Fuel

Since the FDA approved rosiglitazone in May 1999, there have been concerns about adverse lipid effects, edema and increased cardiovascular risk.[1] Nissen and Wolski’s 2007 meta-analysis of 42 clinical trials drew special attention to increased death and disability from cardiovascular complications in patients treated with rosiglitazone; thus many questions have been raised regarding the safety of this drug.[2] In 2007, the FDA revealed similar results in a separate meta-analysis showing a statistically significant increase in cardiovascular risk with the use of rosiglitazone.[3] The manufacturers of rosiglitazone therefore felt compelled to release an interim analysis of the RECORD Trial in 2007, with final results published in 2009. The RECORD Trial supports that the addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes does indeed increase the risk of heart failure. However, the data were inconclusive about any possible effect on myocardial infarction, and it suggested no increased risk of overall cardiovascular morbidity or mortality in those treated with rosiglitazone compared with standard glucose-lowering drugs.[4] The RECORD Trial was criticized as being underpowered and flawed by the publication of unblinded, preliminary data.[5] In June 2009, the FDA therefore mandated an adequately powered cardiovascular outcomes study for rosiglitazone known as the TIDE Trial. In July 2010, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee joint meeting with the Drug Safety and Risk Management Advisory Committee convened. At this meeting, Dr. Nissen (Cardiovascular Medicine Chairman of the Cleveland Clinic) presented an updated meta-analysis which again demonstrated an increased risk of AMI associated with rosiglitazone.[6] In addition, Dr. Graham (Associate Director of the FDA’s Office of Drug Safety) presented the results of the retrospective cohort study discussed here, also suggesting adverse cardiovascular events associated with the use of rosiglitazone. A representative from the manufacturers of rosiglitazone was also present at the joint meeting to defend its product utilizing results from the RECORD Trial. One week following the advisory committee meeting, the FDA announced that the TIDE Trial has been placed on partial clinical hold, with no new patients eligible for enrollment until further notice. In addition, the FDA has instructed the manufacturers of rosiglitazone to update their investigators, institutional review boards and ethics committees involved in the TIDE Trial regarding any new safety information, along with information concerning the deliberations and votes of the FDA joint advisory committee meeting. The FDA is currently still evaluating all available information on rosiglitazone’s safety, in conjunction with discussions of the recent advisory committee meeting, and will update the public on the outcome of its review and its implications for both the TIDE Trial and rosiglitazone.

Revisiting the Rosiglitazone Story — Lessons Learned

In July 2007, 24 members of the Endocrinologic and Metabolic Drug Advisory Committee (EMDAC) and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) held a joint meeting, which I chaired, and concluded that rosiglitazone, an insulin-sensitizing agent used in treating type 2 diabetes mellitus, was associated with an increased risk of myocardial ischemia.1 This conclusion was based on concordant evidence from three independent meta-analyses performed by the drug's sponsor, the FDA, and Nissen and Wolski.1,2 Nevertheless, the committee voted, as did I, to keep rosiglitazone on the market, although we recommended enhancing . . .

FDA: Avoid Clopidogrel With Omeprazole

FDA: Avoid Clopidogrel With Omeprazole

Safety of Long-Acting β-Agonists: Are New Data Really Required?

Safety of Long-Acting β-Agonists: Are New Data Really Required?

Risks of Long-Acting Beta-Agonists in Achieving Asthma Control

In early December 2008, the Food and Drug Administration (FDA) held an unusual joint meeting of the Pulmonary–Allergy Drugs Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee to consider the safety of long-acting beta-agonists (LABAs). The meeting is described in detail in a Perspective in this issue of the Journal by Kramer,1 who points out that decision making by the advisers and the FDA was hampered by the lack of data about the safety of LABAs. LABAs, which are administered by inhalation, act by effecting prolonged stimulation of the β2-adrenergic receptor. . . .