MedWatch Reports Research Articles

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.

Fluoroquinolones: A hot topic for pharmacists and the Food and Drug Administration’s Division of Drug Information

ObjectivesThe Division of Drug Information (DDI) within the U.S. Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research receives telephone calls, e-mails, and letters from patients and industry. The consistently high number of contacts about drugs in the fluoroquinolone class indicates an opportunity to increase awareness about the drugs’ evolving safety profile. Data sourcesDatabase used by DDI to summarize inquiries. SummaryInquiries about fluoroquinolones peaked in 2016 and were highest after FDA Drug Safety Communications that were issued that year. Among the first fluoroquinolone, ciprofloxacin, was approved in 1987. Since then, the FDA has required class-wide labeling changes reflecting postmarket benefit-risk assessments of oral and injectable (systemic) fluoroquinolones, including changes in 1990, 2008, 2013, 2016, and 2018. ConclusionPharmacists have a role that is more critical than ever to ensure the safety of patients who are prescribed a systemic fluoroquinolone. Pharmacists should stay informed on this class of drugs, be prepared to suggest alternate therapies, counsel patients on potential benefits and risks, and work with patients to submit Medwatch reports to the FDA if adverse events occur.

Development of an automated assessment tool for MedWatch reports in the FDA adverse event reporting system.

As the US Food and Drug Administration (FDA) receives over a million adverse event reports associated with medication use every year, a system is needed to aid FDA safety evaluators in identifying reports most likely to demonstrate causal relationships to the suspect medications. We combined text mining with machine learning to construct and evaluate such a system to identify medication-related adverse event reports. FDA safety evaluators assessed 326 reports for medication-related causality. We engineered features from these reports and constructed random forest, L1 regularized logistic regression, and support vector machine models. We evaluated model accuracy and further assessed utility by generating report rankings that represented a prioritized report review process. Our random forest model showed the best performance in report ranking and accuracy, with an area under the receiver operating characteristic curve of 0.66. The generated report ordering assigns reports with a higher probability of medication-related causality a higher rank and is significantly correlated to a perfect report ordering, with a Kendall's tau of 0.24 ( P = .002). Our models produced prioritized report orderings that enable FDA safety evaluators to focus on reports that are more likely to contain valuable medication-related adverse event information. Applying our models to all FDA adverse event reports has the potential to streamline the manual review process and greatly reduce reviewer workload.

The benefit of integrating safety data from the FDA mandated registry with medwatch reports: A Southern Network on Adverse Reactions (SONAR) analysis based on the Tysabri Outreach Commitment to Health Registry (TOUCH).

e18237Background: Natalizumab is an effective therapy for multiple sclerosis. Its most notable toxicity is PML. The FDA mandated registry, TOUCH, focuses on PML cases. We identified an unusual case...

Adverse Events Associated With Sodium Phosphate (Saline) Enema in Adults: A 46-Year Database and Clinical Survey

Introduction: Sodium phosphate enemas are marketed in the U.S. for treatment of occasional constipation and as a bowel preparation. In January 2014, the FDA issued a Safety Communication warning that use of more than one sodium phosphate enema [SPE] in a 24-hour period could cause rare but serious cardiac and renal effects. This study sought to evaluate U.S. adverse event reporting for SPE among adults and to assess U.S. gastroenterologists' [USGI] knowledge regarding the dosing of SPE. Methods: All U.S. adverse event [AE] reports associated with SPE use in adults > 12 yrs were reviewed during the period from June 1968 through December 2014. Sources included an enema manufacturer's safety database, medical literature, and FDA MedWatch reports. Events associated with oral sodium phosphate were excluded. Serious AEs [SAE] and non-serious AEs [NSAE] were defined by the FDA Code of Federal Regulations. Overdose was defined as use of more than the labeled amount of SPE/24 hrs. A survey evaluating USGI knowledge regarding SPE dosing was conducted in January 2015 using a nationally diverse sample. Results: AEs were reported in 608 subjects (Table 1), including 56 SAE and 552 NSAE. The most frequent SAE was electrolyte disturbance and/or acute kidney injury, occurring in 20/56 cases. Fatality was recorded in 12 cases, including electrolyte disturbance (7) and arrhythmia (3). Overdose was more frequent in SAE compared to NSAE (p < 0.00001). Among fatal SAE, overdose was reported in 8/12 cases (75%) vs. 8/44 non-fatal cases (18.2%; p < 0.001). Only 24% of USGI knew that the maximum recommended SPE dose is one bottle/24 hrs (Table 2). In 15/16 SAE cases identified as overdose, a health care provider improperly dosed the enema.Table 1: Adverse Events Associated with Sodium Phosphate (Saline) Enema (1968-2014)Table 2: Survey of U.S. Gastroenterologists on Sodium Phosphate (Saline) Enema (n=50)Conclusion: Overdose of sodium phosphate enema was significantly associated with both serious adverse events and fatality when compared to non-serious adverse events. A majority of U.S. gastroenterologists are unaware of appropriate enema dosing guidelines. Efforts to educate consumers and clinicians on the proper use of sodium phosphate (saline) enema should be undertaken to reduce the risk of adverse events.

The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement.

Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE Pro(TM), a dietary supplement used for weight loss and/or muscle building. Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required "new dietary ingredient" notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. Vigilant surveillance is required for adverse events linked to the use of dietary supplements.

Reporting standards for adverse events after medical device use in the peripheral vascular system

New York, NY;Phoenix, Ariz; Houston, Tex; London, Ontario, Canada; Delhi, India; Silver Spring, Md; and Lewiston, MeAdverse event reporting after medical device implanta-tion is essential to understanding the safety and perfor-mance of a device. Standardization of reporting attainsgreat importance when comparing different devices andfor the ongoing surveillance of a marketed device.Although some work has been done to standardize adverseevent reporting for medical devices, a single reference withrecommendations that span investigational and postmarketuse does not exist.Standardization of nomenclature for reporting vascularconditions is one of the objectives of the Society forVascular Surgery (SVS) in its Bylaws.

Educating patients about FDA’s MedWatch

Many patients may be unaware of FDA's MedWatch Adverse Reporting Program and the role they can play in helping the agency identify potential safety issues with products in the marketplace. Educating patients about the program, the importance of reporting, and how to submit a report to FDA will aid in safeguarding future patients from potentially serious adverse events.

Feasibility of Proactive Medical Device Surveillance

Timely identification and reporting of medical device problems is critical to postmarket device surveillance programs to maximize patient safety. Cardiac catheterization laboratories are high-device utilization areas well suited for device surveillance. To demonstrate the feasibility of the national VA Clinical Assessment, Reporting, and Tracking (CART) system, embedded in the electronic health record of all 76 VA cardiac catheterization laboratories, to document unexpected problems with medical devices at the point of care. We evaluated 260,258 consecutive cardiac catheterization and/or percutaneous coronary intervention procedures on 175,098 Veterans between August 2006 and February 2012. Unexpected device problems (UDPs) encountered for any equipment used during a procedure were entered by clinicians at the point of care as part of regular care documentation. All UDPs were reviewed in collaboration with the FDA to ascertain the likelihood of a device defect (eg, in manufacture or design) and/or contributing to a procedural complication (level I, unlikely; level II, possibly; level III, likely). Of the 260,258 procedure reports, 974 (0.37%) UDP's were reported by 71 (92.2%) of the 76 VA hospitals. After triage, 739 (75.9%) were deemed level I, 196 (20.1%) level II, and 39 (4.0%) level III. Of the 39 level III reports, 12 (30.7%) are in the submission phase as a FDA MedWatch report. The number of monthly UDP reports increased significantly from 2006 to 2012 (P<0.001). Leveraging a clinical application embedded in the electronic health record and in collaboration with FDA, a proactive national cardiac device surveillance program has been successfully implemented in the VA.

The Importance of Consumer Reporting Side-effects with Regulated Products: The New Consumer Friendly FDA 3500B MedWatch Form

Copyright: © 2013 Phillips L. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The Food and Drug Administration (FDA) has a new voluntary consumer friendly MedWatch Form 3500B [1]. The new MedWatch form uses lay friendly language with a simplified layout making it easier for consumers to report problems with drugs and other regulated products to the FDA. Consumer reports to the MedWatch system are increasing [2] and have been shown to make a difference in recognizing new and serious drug adverse events. Consumers often have the most details about what they are experiencing, and are in a unique position to identify new safety signals earlier. Every Medwatch report is important; a single report can identify a safety problem and prompt the FDA into action. Recent Consumer reports alerted scientists at the FDA to a critical health issue about the accidental exposure and harm to children from to Testosterone gel used by Men [3]. These early reports prompted the FDA to mandate stronger warning labels that required that the gel be covered after applying to the skin so other people would not be exposed [3].

Immune reconstitution inflammatory syndrome in natalizumab-associated PML

To study the outcome of patients with multiple sclerosis (MS) and with natalizumab-associated progressive multifocal leukoencephalopathy (PML) and immune reconstitution inflammatory syndrome (IRIS). MedWatch reports from Biogen-Idec (manufacturer of natalizumab, Tysabri(®)) were reviewed which comprised all 42 cases of natalizumab-related PML cases since its reintroduction until March 2010. All except 2 patients with natalizumab-related PML were managed by discontinuation of natalizumab and plasmapheresis/immunoadsorption (PLEX/IA). Seventeen patients had contrast enhancement of PML lesions on neuroimaging at the time of diagnosis before withdrawal/removal of natalizumab (early-PML-IRIS) and 23 patients developed contrast enhancement only after withdrawal/removal of natalizumab (late-PML-IRIS). All patients developed IRIS. IRIS was defined as worsening of neurologic deficits during the immune reconstitution following discontinuation of natalizumab, corroborated by inflammatory changes on neuroimaging. Following PLEX/IA, JC viral load in CSF increased by >10 fold in those with early-PML-IRIS but <2 fold in late-PML-IRIS. IRIS developed earlier and was more severe in early-PML-IRIS (p < 0.05). At the last follow-up, all patients had worse EDSS scores but this was higher in patients with early-PML-IRIS compared to those with late-PML-IRIS (p > 0.05). Mortality was comparable between the 2 groups, 29.4 ± 11% vs 21.7 ± 8.8%. Corticosteroid therapy during IRIS was associated with better Expanded Disability Status Scale outcome, p < 0.05. Early immunologic rebound in natalizumab-associated PML has worse survival and neurologic outcome. PLEX/IA may accelerate IRIS and its impact on the final outcome is unclear. Corticosteroid therapy provides a modest benefit and needs to be systemically studied in a controlled manner in the management of natalizumab-associated PML-IRIS.

Hematologic adverse events associated with temozolomide

Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to the FDA from November 1, 1997 to September 3, 2008. We defined major HAEs, namely agranulocytosis, aplasia, aplastic anemia (AA), leukemia (various), myelodysplastic syndrome (MDS), and lymphoma, and several minor HAEs. A total of 5,127 reports on 3,490 patients were submitted to MedWatch. Among these, we identified 112 cases of major HAEs. Of the 44 reported deaths, the major HAE was considered the cause in 32 cases. The median duration of TMZ treatment was 6weeks [0.5-108weeks]. Seventy-six cases of AA or aplasia and 17 cases of leukemia represented the most common major HAE. Important minor HAEs were bone marrow failure and pancytopenia/pancytopenia-like with 325 combined cases; these reports are clinically similar to aplastic anemia. The hematologic toxicity profile of TMZ differs from that of other alkylating agents. TMZ HAEs are emerging as significant concerns. Among alkylating agents, AA appears unique to TMZ, and the high rate warrants disclosure of patients. The duration of TMZ exposure prior to the development of AA may be quite short. The risk of AML/MDS is low, but the length of follow-up is insufficient to assess the true risk.

A web-based medical safety reporting system for a large multicenter clinical trial: The ALIAS experience

An electronic safety reporting (ESR) module was developed and integrated into a home-grown web-based clinical trial management system (CTMS) to enhance the efficiency, completeness and consistency of reporting and reviewing serious adverse events, monitoring safety, and submitting safety reports to regulatory authorities for a large multicenter clinical trial. The architecture of this integrated module provided many advantages. First, the ESR module was developed based on a comprehensive procedure which incorporated both computer logic processing steps and human intervention steps in order to deal with the complex and unexpected situations where pre-programmed computer logic may fail. Second, safety and efficacy data were managed within the same relational database. Relevant data captured on efficacy case report forms, such as demographics, medical history, lab data and concomitant medications, were directly retrievable for MedWatch report composition without requiring redundant data entry. Finally, the ESR module shared the same generic user interfaces and data processing functions with other modules in the CTMS. These generic components include data editing, data retrieving, data reporting, dictionary-based automatic and interactive coding, event-driven and calendar-driven automatic email notifications, and user privilege management. This integrated ESR module was implemented in the Albumin in Acute Stroke (ALIAS) Trial—Part 1. A total of 397 serious adverse event reports were processed and 33 FDA MedWatch reports, 28 initial reports, and 5 follow-up reports were submitted to FDA and Health Canada using this system. Experiences and lessons learned from the development and implementation of this system are presented in this paper.

The FDA extended warning for intravenous haloperidol and torsades de pointes: How should institutions respond?

In September 2007, the Food and Drug Administration (FDA) strengthened label warnings for intravenous (IV) haloperidol regarding QT prolongation (QTP) and torsades de pointes (TdP) in response to adverse event reports. Considering the widespread use of IV haloperidol in the management of acute delirium, the specific FDA recommendation of continuous electrocardiogram (ECG) monitoring in this setting has been associated with some controversy. We reviewed the evidence for the FDA warning and provide a potential medical center response to this warning. Cases of intravenous haloperidol-related QTP/TdP were identified by searching PubMed, EMBASE, and Scopus databases (January 1823 to April 2009) and all FDA MedWatch reports of haloperidol-associated adverse events (November 1997 to April 2008). A total of 70 of IV haloperidol-associated QTP and/or TdP were identified. There were 54 reports of TdP; 42 of these events were reportedly preceded by QTP. When post-event QTc data were reported, QTc was prolonged >450 msec in 96% of cases. Three patients experienced sudden cardiac arrest. Sixty-eight patients (97%) had additional risk factors for TdP/prolonged QT, most commonly receipt of concomitant proarrhythmic agents. Patients experiencing TdP received a cumulative dose of 5 mg to 645 mg, patients with QTP alone received a cumulative dose of 2 mg to 1540 mg. While administration of IV haloperidol can be associated with QTP/TdP, this complication most often took place in the setting of concomitant risk factors. Importantly, the available data suggest that a total cumulative dose of IV haloperidol of <2 mg can safely be administered without ongoing electrocardiographic monitoring in patients without concomitant risk factors.

Cefepime Is Not Associated with Increased Mortality

On June 17, 2009, the FDA updated healthcare providers about its ongoing safety review of cefepime. The initial MedWatch report, issued in November

A Near Miss: A Nitrous Oxide-Carbon Dioxide Mix-up Despite Current Safety Standards

A Near Miss: A Nitrous Oxide-Carbon Dioxide Mix-up Despite Current Safety Standards

Erythropoiesis stimulating agents (ESAs): An overview of safety-related findings from the Research on Adverse Drug Events and Reports (RADAR) project

6635 Background: ESAs were approved in 1989 and 1993 for treatment of anemia associated with chronic kidney disease (CKD) or chemotherapy-associated anemia, respectively. Since then, clinicians have viewed ESAs as having little toxicity. Methods: We reviewed case studies and epidemiologic assessments of relative risks (RR) and hazard rates (HR) of ESA-associated toxicity in the setting of CKD and cancer. Data sources included meta-analyses, randomized clinical trials, and FDA MedWatch reports. Results and Conclusions: While safety signals for ESA-associated toxicity were first reported in 1998 (Besarab et al; the Normal Hematocrit Trial), most serious ESA- associated toxicities were not reported until 2002 or later- 13 years after epoetin first received FDA approval. Pharmacovigilance efforts require commitment to conduct focused long-term safety studies especially when commonly used drugs have small RR for toxicity/death. Toxicity Setting # of Cases/Rates Reference Cardiovascular toxicity CKD RR=1.24 NEJM1998 Pure Red Cell Aplasia CKD 191/4.5 per 10,000 (Eprex) NEJM2002 NEJM 2005 Tumor Progression Anemia of Ca RR=1.39 Lancet 2003 Counterfeit Drug Cancer n=7/RR not known ASH 2005 Venous thromboembolism All cancers n=172/760 per 10,000 JNCI 2005 Venous thromboembolism Myeloma n=20/2,300 per 10,000 NEJM 2005 Gadolinium Nephrogenic Systemic Fibrosis CKD 22/RR not known Annals 2006 Mortality CKD RR= 1.29 Lancet 2007 Mortality Anemia of Ca RR=1.39 NEJM 2007 Mortality Ca-associated anemia RR= 1.39 Lancet 2007 Locoregional progression Head/neck Ca RR= 1.69 NA Leukemic transformation Primary myelofibrosis n=22/HR =3.1 ASH 2007 Mortality Cancer/CKD RR = 1.3 (cancer); 1.3 (CKD) ASH 2007 JAMA 2008 No significant financial relationships to disclose.

Infections and human tissue transplants: review of FDA MedWatch reports 2001–2004

More than 1.5 million tissue allografts are transplanted annually in the U.S. As part of the federal effort to improve tissue safety, FDA's May 2005 Current Good Tissue Practices (CGTP) Rule requires tissue establishments to report to FDA serious infectious adverse events following allograft transplantation. To provide baseline data, we summarize reports of such infections received by FDA prior to the CGTP Rule. We reviewed reports received by FDA's MedWatch adverse event reporting system during 2001-2004. Our case definition was a reported infection in a human tissue transplant recipient within 1 year of transplantation. We examined demographics, tissue type, clinical outcomes and interventions, infectious organism(s), time from transplant to infection and reporter characteristics. We identified 83 reports of infections following allograft transplantations. Median patient age was 40 years (range: 1 month-87 years). The allografts included heart valves (42%), tendons (33%), bones (8%), blood vessels (6%), ocular tissues (5%), and skin (4%). Commonly reported outcomes and interventions were hospitalization (72%), antibiotic therapy (46%) and graft removal (42%). Nine of 11 patients who expired had received heart valves. In 65 reports that identified suspected organisms, bacteria were most common (42), followed by fungi (25) and prions (1). The median time from transplant to infection was 5.5 weeks (range: 3 days-52 weeks). Tissue manufacturers submitted 26% of reports. Among the remaining 74%, the reporters were quality assurance staff, infection control or risk management personnel (45%); physicians (15%); consumers (15%); nurses (13%); and surgical staff (12%). This is the first review of reports to FDA for infections following allograft tissue transplantations. Infections led to serious outcomes and involved many tissue types. Although we were unable to confirm that reported infections were caused by the suspected tissue product, required reporting by tissue establishments and improvements in adverse event investigation will help to improve tissue safety surveillance.

Inadvertent Intrathecal Administration of Vincristine.

Background: Vincristine is a vesicant drug which is normally given intravenously. Intrathecal administration of vincristine is a therapeutic misadventure, causing chemical leptomeningitis and focal ventriculitis. While 55 cases of intrathecal vincristine administration have been reported worldwide, only 32 cases have been documented in the literature, 13 have been reported to the FDA Med Watch, and many more cases are believed to be unreported. Of the documented cases, 84.3% resulted in death and 15.6% of those who survived had serious neurological consequences such as quadriplegia and paraplegia.Methods: The Research on Adverse Events and Reports (RADAR) project conducted a review of literature published between 1968 and June 2006. Sources included Med Watch reports, published abstracts and journal articles, online newsletters, and letters from pharmacists.Findings: The reports reviewed showed that intrathecal administration of vincristine occurred most often because of inadequate communication between pharmacy and medical staff (22 of 32 cases; 68.7%). In these cases, the pharmacy mistakenly delivered vincristine syringes together with syringes containing intrathecal medications and physicians or nurses wrongly administered vincristine intrathecally. Pharmacy error alone, such as the mislabeling of syringes, accounted for 6 of 32 cases of intrathecal administration of vincristine (18.7%) while physician/nurse error alone (failure to read syringe labeling or check physician's orders) accounted for 4 of 32 cases (12.5%).Conclusions: Since vincristine is lethal when given intrathecally, its administration should be executed with the precautionary measures employed with other potentially lethal substances, such as blood products. Carefully reviewing physician orders before drug administration and dispensing vincristine in syringes incompatible with spinal needles can also curb fatal error. Other preventive measures include properly labeling vincristine syringes for intravenous use only and diluting vincristine in intravenous mini-infusion bags.Literature review of case reports since 1968< 19851986–19901991–19951996–20002001–2005TotalUSA/Canada7124216Europe002215Australia011013Asia101305Total Cases8268832Deaths8146827 (84.3%)Pharmacy/medical staff error5135522 (68.7%)Pharmacy error202236 (18.7%)Physician/Nurse error111104 (12.5%)

Counterfeit Epoetin: A Review of MedWatch Data.

Introduction: In 2002 and 2003, Ortho Biotech Products, L.P. issued “Dear Health Professional” letters describing two distinct episodes with distribution of counterfeit epoetin (ProcritÒ). The first episode in 2002 occurred when counterfeit labels marked as “40,000 Unit” vials were switched onto 2,000 Unit Procrit vials (5% potency). An estimated 97,000 vials of this product were not recovered, as many as 25,000 patients may have been exposed. A second episode occurred in 2003 when bacteria-contaminated tap water was added to vials that were labeled as containing “40,000 Units” of Procrit®. The “Dear Doctor” letters describe the subtle labeling and other product packaging features that distinguish the products from authentic. In addition, specific lot numbers are identified. We reviewed all MedWatch reports from the United States' Food and Drug Administration (FDA) for confirmed or possible cases of counterfeit epoetin.Methods: For the years 1998 to 2004, the FDA's adverse event reporting system (AERS) was searched, using key words: “suspected product tampering,” “decreased drug effect” and related terms, and all epoetin product names. We summarized the demographic variables for the cases and identified the lot numbers reported within the cases.Results: Seven cases of “medication tampering” were identified in the FDA's Adverse Event Reporting System (AERS) database - all 7 included Procrit® lot numbers identified in the “Dear Health Professional” Warning Letters from OrthoBiotech. The cases had been reported to the FDA by pharmacists (n=5), a consumer (n=1), and a nurse (n=1). In six of these case reports, among cancer patients, death also listed on the report, although counterfeit product was not listed as the proximate cause of death. There were no case reports identified by the diagnostic term of “pharmaceutical product counterfeit”, which was added to the FDA's AERS in 2004. We identified an additional 643 cases of MedWatch cases that were coded with the diagnostic labels of “drug ineffective”, “therapeutic response decreased”, “drug effect decreased”, “condition aggravated”, and similar terms. The mean age equal to 59.7± 17.7 years, range 5–95 years. There were 269 females (42%) and 358 males (55%), gender not reported for 3%. All epoietin products were included. Finally, one case was found with a reported lot number corresponding to one listed in the warning letters. Death occurred in this 89 year-old patient.Conclusion: Health professionals should be alert for potential counterfeit drugs whenever drug effects are less than expected and the pharmaceutical is costly. Whenever suspected, the occurrences should be reported to the FDA and the manufacturer as possible “pharmaceutical product counterfeit.” The use of radio frequency identification (RFID), planned to be implemented in 2007 may help prevent the domestic distribution of counterfeit drugs, but increases in direct importation of drugs from international sources will potentially increase the likelihood of distribution of counterfeit drugs domestically.