US Food and Drug Administration (FDA) Emergency Use Authorization: Glass Half Full or Glass Half Empty?

Recently, the US Food and Drug Administration (FDA) issued emergency use authorization (EUA) for convalescent plasma (CP) for the treatment of hospitalized patients with coronavirus disease 2019 based on a non-peer-reviewed, open-label, observational study. Issuance of an EUA without a proven randomized, controlled trial (RCT) sets a dangerous precedent since the premature action drives healthcare providers and patients away from RCTs that are essential for determining the efficacy and safety of CP. More caution should have been taken based on what was learned from the recent debacle related to the rescinded EUA of hydroxychloroquine and chloroquine, which were approved initially based on an anecdotal report. The FDA process for determining efficacy and safety must be based solely on data from RCTs in order to sustain public and professional trust for future treatment and vaccine efforts to be successful.

Risk of major morbidity and death in older adults with suicidal intent: a cross-sectional analysis from the National Poison Data System, 2000-2009.

OBJECTIVES: To describe suicide-related exposures in older persons according to sex, age, and substance category reported to U.S. poison control centers (PCCs) and report the crude relative risk (RR) of major effects and death from pharmaceuticals and nonpharmaceutical substances after single- and multiple-substance exposures. DESIGN: Cross-sectional analysis of American Association of Poison Control Centers National Poison Data System (NPDS) data. SETTING: Calls to U.S. PCCs. PARTICIPANTS: NPDS cases involving individuals aged 60 and older with an exposure to a pharmaceutical or nonpharmaceutical substance and suicide as the reason (n=46,494). MEASUREMENTS: Major effect and death probabilities for single- and multiple-substance exposures to pharmaceuticals and nonpharmaceuticals were determined. In the NPDS, a major effect is defined as symptoms or signs that are life-threatening or resulted in significant residual disability or disfigurement. Crude RRs of major effects or death were estimated for single and multiple pharmaceutical substances in comparison with nonpharmaceutical substances. RESULTS: Single-substance exposures occurred in 53.3% of cases. Overall, 92.3% involved pharmaceuticals and 64.4% involved women. In the total sample, 12.7% (5,895/46,494) of exposures resulted in major effect, and 1.9% (884/46,494) resulted in death. The crude RR of major effects in single-substance pharmaceutical exposures was significantly lower than with nonpharmaceutical exposures (RR=0.54, 95% confidence interval (CI)=0.49-0.59), as was death (RR=0.25, 95% CI=0.20-0.30). For multiple-substance exposures, the crude RR of major effects from pharmaceuticals was similar to that for nonpharmaceuticals (RR=0.92, 95% CI=0.80-1.06), whereas the crude RR of death from pharmaceuticals was significantly lower (RR=0.55, 95% CI=0.40-0.77). CONCLUSION: These findings can inform suicide prevention strategies that focus on decreasing at-risk older adults' access to dangerous medications and chemicals in the home.

Poisoning in the United States: 2012 emergency medicine report of the National Poison Data System.

Deaths from drug overdose have become the leading cause of injury death in the United States, where the poison center system is available to provide real-time advice and collect data about a variety of poisonings. In 2012, emergency medical providers were confronted with new poisonings, such as bath salts (substituted cathinones) and Spice (synthetic cannabinoid drugs), as well as continued trends in established poisonings such as from prescription opioids. This article addresses current trends in opioid poisonings; new substances implicated in poisoning cases, including unit-dose laundry detergents, bath salts, Spice, and energy drinks; and the role of poison centers in public health emergencies such as the Fukushima radiation incident.

The opioid abuse and misuse epidemic: implications for pharmacists in hospitals and health systems.

PURPOSE: The current epidemic of prescription opioid abuse and misuse in the United States is discussed, with an emphasis on the pharmacist's role in ensuring safe and effective opioid use. SUMMARY: U.S. sales of prescription opioids increased fourfold from 1999 to 2010, with an alarming rise in deaths and emergency department visits associated with the use of fentanyl, hydrocodone, oxycodone, and other opioid medications. Signs and symptoms of opioid toxicity may include altered mental status, hypoventilation, decreased bowel motility, central nervous system and respiratory depression, peripheral vasodilation, pulmonary edema, hypotension, bradycardia, and seizures. In patients receiving long-term opioid therapy for chronic pain, urine drug testing is an important tool for monitoring and assessment of therapy; knowledge of opioid metabolic pathways and assay limitations is essential for appropriate use and interpretation of screening and confirmatory tests. In recent years, there has been an increase in federal enforcement actions against pharmacies and prescription drug wholesalers involved in improper opioid distribution, as well as increased reliance on state-level prescription drug monitoring programs to track patterns of opioid use and improper sales. Pharmacies are urged to implement or promote appropriate guidelines on opioid therapy, including the use of pain management agreement plans; policies to ensure adequate oversight of opioid prescribing, dispensing, and waste disposal; and educational initiatives targeting patients as well as hospital and pharmacy staff. CONCLUSION: Pharmacists in hospitals and health systems can play a key role in recognizing the various forms of opioid toxicity and in preventing inappropriate prescribing and diversion of opioids.

Amoxicillin renal toxicity: how often does it occur?

OBJECTIVES: To determine the incidence of renal symptoms associated with amoxicillin, a retrospective review of exposures to amoxicillin in children younger than 6 years as reported to the National Poison Data System was done. METHODS: All ingestions of amoxicillin without coingestants in humans younger than 6 years reported to the National Poison Data System from 2004 through 2008 were analyzed. Data included age, sex, management site, outcome, symptoms, amount ingested, certainty of amount, chronicity, weight, and therapy. The study was approved by the institutional review board. Descriptive statistics were used to characterize the data. RESULTS: A total of 14,717 cases were identified. Related renal symptoms occurred in 5 patients (0.03%). In 1687 patients (9.6%), the total amount (in milligrams) was documented, and the median amount ingested was 1000 mg. In patients with a known amount (in milligrams) along with the child's weight (n = 1356), the median amount was 82.6 mg/kg. In this group, 213 ingested greater than 250 mg/kg (range, 251.4-1531.1 mg/kg; median, 366.5 mg/kg). Treatment sites for this group included the following: treated in the home, 129 (60.6%); treated and released from an health care facility, 63 (29.6%); treated while admitted, 2 (0.9%); refused a referral, 7 (3.3%); lost to follow-up, 9 (4.2%); and managed at other sites, 3 (1.4%). Within this group, 94 patients (44.1%) were followed up to a definitive outcome: 77 (81.9%) had no effect, 15 (16.0%) had minor symptoms, and 2 (2.1%) had moderate symptoms. CONCLUSIONS: Although renal toxicity may occur with amoxicillin ingestions, it is rare and does not seem to be dose related.

Evaluation of pharmacist utilization of a poison center as a resource for patient care.

The objective of this study was to evaluate pharmacist use of a Regional Poison Information Center (RPIC), identify potential barriers to utilization, and provide strategies to overcome these barriers. All calls placed to a RPIC by a pharmacist, physician, or nurse over a 5-year period were retrieved. These data were analyzed to assess the pharmacist utilization of the RPIC and the variation of call types. Additionally, a survey, designed to assess the past and future use of the RPIC by pharmacists, was distributed to pharmacists in the region. Of the 37,799 calls made to the RPIC, 26,367 (69.8%) were from nurses, 8096 (21.4%) were from physicians, and 3336 (8.8%) were from pharmacists. Among calls initiated by pharmacists, the majority involved medication identification (n = 2391, 71.7%). The survey had a 38.9% response rate (n = 715) and revealed a trend toward less RPIC utilization by pharmacists with more formal training but less practice experience. The utilization of the RPIC was lowest among pharmacists as compared to other health care professionals. This may be due to pharmacists' unfamiliarity with the poison center's scope of services and resources. Therefore, it is important that pharmacists are educated on the benefit of utilizing poison centers in clinical situations.

Confusion: acetaminophen dosing changes based on NO evidence in adults.

Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?

Whole fentanyl patch ingestion: a multi-center case series.

BACKGROUND: Fentanyl is a potent synthetic opioid with large abuse potential. A common preparation of fentanyl is a sustained-release transdermal patch. To our knowledge, there are only two published case reports of whole patch ingestion. A case series of 76 patients with a history of whole patch ingestion is reported. STUDY OBJECTIVES: To characterize whole fentanyl patch ingestion to develop a clinical guideline for management. METHODS: This was a retrospective review of all patients who ingested intact fentanyl patches as reported to three regional poison information centers (RPIC) from 2000 to 2008. The three RPIC medical record databases were queried for all exposures with a substance code matching the Micromedex® (Thomson Reuters, New York, NY) fentanyl product codes. Collected data included: age, gender, reason for the exposure, number of patches ingested, dose (µg/h), symptoms, symptom onset and duration, treatment hospital flow (level of care), and outcome. RESULTS: A total of 76 patients met the inclusion criteria. Two patients had both time of onset and symptom duration documented. In both patients, the signs and symptoms developed within 2 h of the exposure, and the patients were asymptomatic at 6½ and 9 h, respectively. Fifty-eight (78.3%) patients were admitted. Of those patients who were admitted, 56 (96.5%) were admitted to a critical care unit. Fourteen patients required intubation, and naloxone infusions were documented in eight cases. CONCLUSION: Ingestion of whole fentanyl patches may lead to prolonged and significant toxicity based on these poison center data.

A regional poison information center IVR medication identification system: does it accomplish its goal?

BACKGROUND: The 2009 AAPCC NPDS report identified 1,057,632 medication identification requests to poison information centers. This represents 24.7% of all calls to US poison information centers. To reduce the impact of medication identification requests on a poison information center, a regional poison information center developed and implemented an automated medication identification system that utilized an interactive voice response (IVR) system. The objective of this project was to describe how the IVR affected the regional poison information center medication identification request call volume and workload of the staff. METHODS: All documented medication identification request inquiries from January 1, 2007 through June 30, 2011 were extracted from the RPIC Visual Dotlab electronic medical record system. Descriptive statistics, presented as means, were used to characterize the monthly call volume inquiries. RESULTS: Over the 18 months (January, 2007 to June, 2008) preceding the implementation of the IVR medication identification request system, a mean of 4,389.6 medication identification requests per month required manual electronic documentation by SPI. In the immediate 12 months (August, 2008 to July, 2009) following the IVR medication identification request system implementation, a mean of 2132.6 inquiries per month (54% reduction) were managed by the IVR. During the 12 month period of July, 2010 through June, 2011, the combined monthly mean of medication identification requests documented by SPI and the IVR decreased to a total of 686.7 compared to the mean pre-implementation monthly total of 4,389.6. CONCLUSIONS: The IVR medication identification request system was successful in reducing the number of medication identification requests that required manual electronic documentation by SPI and freed up a substantial amount of time for SPI to perform other critical patient care-related responsibilities. The enhanced technology that was implemented to improve efficiency came with the unintended consequence of discouraging the public from using the RPIC medication identification service as extensively.

Friends and foes in the plant world: a profile of plant ingestions and fatalities.

INTRODUCTION: Plants are beneficial as foodstuffs and many have medicinal properties. However, some plants also have the potential to produce toxicity. The objective of this study was to characterize plant exposures that involve humans and to discuss those that are associated with morbidity and mortality, as well as some that have undeserved bad reputations. MATERIALS AND METHODS: The American Association of Poison Control Centers (AAPCC) 1983-2009 annual reports were reviewed to identify all plant-related fatalities. The 2000-2009 AAPCC Toxic Exposure Surveillance System and the National Poison Data System databases were queried to identify all plant ingestions. The data were analyzed to identify the specific plants, the age and gender of those who were exposed, the reason for the exposures and patient outcome. RESULTS: During the decade of 2000-2009, 668 111 plant ingestion exposures were reported, 621 109 were single substance exposures with no co-ingestants, and the age was known in 611 708 of the exposures. There has been a steady decline in the number of plant exposures reflected as a percentage of all exposures reported to US poison centers. A total of 8.9% of all exposures involved plants in 1983, 6.0% in 1990, 4.9% in 2000, and 2.4% in 2009. Males accounted for 52.2% of the ingestions and over 60% of the moderate and major outcomes occurred in males. Morbidity was related directly to the reason for the exposure with the most severe outcomes occurring in those who ingested plants intentionally for self-harm or substance abuse. Children ≤5 years of age accounted for 81.2% of plant ingestion exposures. Within this age category, there were 497 002 ingestions over the 10-year period where a known age was recorded and 57.8% occurred in children less than 1 year of age. Only 45 fatalities were recorded between 1983 and 2009. Datura and Cicuta species were responsible for 35.5% of the fatal outcomes. CONCLUSIONS: Plant ingestion exposures remain a common call to poison information centers. However, the volume of those calls has decreased steadily over the last three decades. Most plant ingestion exposures occur in children, specifically children ≤5 years of age. Within this age group, there were an inordinate number of exposures in children <1 year of age, a previously unidentified finding with an unknown epidemiological basis. Morbidity and mortality associated with plant ingestion exposures were very low relative to the total number of reported exposures.

Cost minimization analysis comparing enteral N-acetylcysteine to intravenous acetylcysteine in the management of acute acetaminophen toxicity.

CONTEXT: Acetaminophen poisoning is one of the most common exposures and causes of poisoning-related fatalities as reported to U.S. poison information centers. Acetylcysteine is indicated for the antidotal treatment of acetaminophen poisoning to prevent or minimize acetaminophen-related hepatotoxicity. Available as either an enteral or intravenous (IV) formulation, both forms of acetylcysteine have been proven to be efficacious. Because of the differences in the acquisition costs and the length of treatment, it is unclear which treatment route is the most cost-effective. OBJECTIVE: The purpose of this study was to compare the total hospitalization charges associated with patients who received either enteral or IV acetylcysteine therapy. MATERIALS AND METHODS: A retrospective, IRB-approved cohort study of patients treated with either enteral or IV acetylcysteine at a university-related hospital for the treatment of acute acetaminophen overdose was conducted. Patients included were over 18 years of age, admitted during the 5-year periods of 1996-2000 (enteral) and 2004-2008 (IV), had an ICD-9 discharge diagnosis for acetaminophen overdose, had no transplant history, and were admitted within 24 h of the overdose. The primary endpoint was the total cost associated with the hospital stay. The Consumer Price Index (CPI) inflation calculator from the U.S. Bureau of Labor Statistics was used to adjust all monetary values to 2008 dollars. RESULTS: Of a total of 1,647 patients, 261 met the inclusion criteria with 70 patients being treated with enteral acetylcysteine and 191 patients treated with IV acetylcysteine. The associated cost was greater in the enteral group than in the IV group ($18,287.63 vs. $7,607.82; p < 0.001). The average length of stay was longer in the enteral group compared to the IV group (7 days vs. 4 days; p < 0.001). CONCLUSIONS: Patients who were treated with IV acetylcysteine had a decreased length of stay and cost of hospitalization compared with those patients who were treated with enteral acetylcysteine.