Consumers adverse event reporting

FDA does not want reports on every adverse event observed that would not be practical for reporters or FDA because of the sheer volume of adverse-event reports already being sent to the agency each year (about 130,000 in 1994). While 80-85% of these reports are submitted by the manufacturer, 10-15% are received by MedWatch directly from physicians, pharmacists, other health care professionals, and consumers. MedWatch encourages reporters to be selective by limiting their reports to events for which the outcome was serious (Table 20.2). This enables FDA to focus on those events with potentially the largest public health impact. Reporters are encouraged to fill out the reporting form as completely and accurately as possible. 

DSHEA severely limited when the FDA could take action to protect the public and what actions could be taken. The burden of proof to show harm is now placed on the FDA. Moreover, dietary supplement manufacturers are not required to report adverse dietary supplement events. In fact, between 1994 and 1999 fewer than 10 of the 2500 adverse events associated with dietary supplements and reported to the FDA were reported by the manufacturer (53). The Office of Inspector General concluded the spontaneous adverse event reporting system has difficulty generating signals of possible public health concern due to limited medical information, product information, manufacturer information, consumer information, and ability to analyze trends (57). One weight loss supplement manufacturer is reported to have withheld from the FDA 14,684 complaints of adverse events regarding ephedra, which included heart attacks, strokes, seizures, and deaths (53). 

Accepts reports from consumers and health professionals about products regulated by the FDA, including drugs and medical devices, through Med-Watch, the FDA s safety information and adverse event reporting program. (800) 332-1088... 

Food and Drug Administration (FDA) Surveillance System. This was developed and is managed by the FDA. As part of this system, all adverse events reports concerning medical products after their formal approval are submitted to the FDA. In the case of medical devices, the device manufacturers report information on items such as deaths, serious injuries, and malfunctions. Furthermore, the device user facilities such as hospitals and nursing homes are required to report deaths to both the FDA and manufacturers and also serious injuries to device manufacturers. In regard to drug-related adverse events, reporting is mandatory for all manufacturers, but it is voluntary for physicians, consumers, and so on [2]. 

The agency is permitted to restrict substances that pose a "significant and rmreasonable risk" rmder the conditions of use on the label or as commonly consumed. The FDA has the burden of proof and cannot act rmtil substantial harm occurs to consumers, but manufacturers are not required to report adverse events. Even when harm is obvious, instituting a ban can take years. For example, even though thousands of consumers appear to have been affected by products that contain ephedra, it took the FDA more than 5 years to go through the procedures needed to ban its use. 

Because of the problems that resulted from self-regulation, another law, the Dietary Supplement and Non-Prescription Drug Consumer Protection Act, was approved in 2006. This law requires manufacturers, packers, or distributors of supplements to submit reports of serious adverse events to the FDA. Serious adverse events are defined as death, a life-threatening event, hospitalization, a persistent or significant disability or incapacity, congenital anomaly or birth defect, or an adverse event that requires medical or surgical intervention to prevent such outcomes based on reasonable medical judgment. If this requirement were enforced, and consumers cooperated, these reports would make it possible to identify trends in adverse effects and would help to alert the public to safety issues. 

Adverse effects have been documented for a variety of dietary supplements however, under-reporting of adverse effects is likely since consumers do not routinely report, and do not know how to report, an adverse effect if they suspect that the event was caused by consumption of a supplement. Furthermore, chemical analysis is rarely performed on the products involved, including those products that are described in the literature as being linked to an adverse event. This leads to confusion about whether the primary ingredient or an adulterant caused the adverse effect. In some cases, the chemical constituents of the herb can clearly lead to toxicity. Some of the herbs that should be used cautiously or not at all are listed in Table 64-1. 

The Special Nutritionals Adverse Event Monitoring System (SN/AEMS) of the U.S. Food and Drug Administration (FDA), a database of consumer reactions to nutritional supplements and substances, has had 31 reports of adverse reactions to products containing creatine between 1993-1998. Reported symptoms include (but were not limited to) ... 

The FDA has been receiving reports of adverse effects related to ephedra use since the early 1990s. Many of the initial concerns were linked to one ephedra product—Formula One. However, when state and federal agencies investigated the product, they could not prove that it contained ephedra, and after the manufacturer of Formula One reformulated the product, reports of adverse events linked with the product ceased. But there have been many reports of adverse events associated with ephedra since 1994. The severity of those events spurred the FDA to action, which sought an independent review in an attempt to determine if ephedra had been the cause. Another purpose of the independent review was to determine the risks of consuming ephedra. 

Ephedra supplements typically contain caffeine, and users may consume caffeine in carbonated beverages, coffee, or tea. Researchers suspect that caffeine may enhance ephedra s stimulant effects on cardiovascular and/or central nervous system responses. This may account for the types of adverse events that have been reported by ephedra users. 

These are unsolicited adverse events that are reported to the company after the drug is on the market. Their sources include consumers, their relatives, clinicians (whether nurses, pharmacists or prescribes) and, occasionally, lawyers or sales representatives (the last even being from other companies). 

MedWatch. URL http //www.fda.gov/medwatch/index.html. The FDA s MedWatch Web site outlines procedures for voluntary reporting of serious adverse events or product problems by consumers and healthcare practitioners. It also includes... 

Reports of ephedra-related stroke on file with the FDA have not yet been published in the peer reviewed literature. In some of the FDA cases, massive doses of ephedrine were consumed (as with products intended for abuse, such as "herbal ecstasy," now withdrawn from the market). In other cases, toxicology testing was not performed, and it is not known with any certainty whether ephedrine was even taken. In still other cases, the drug identified was not ephedrine Many adverse events attributed to ephedrine have actually been due to ephedrine enantiomers, pseudoephedrine (Loizou et al., 1982 Stoessl et al., 1985) and phenylpropanolamine (Johnson et al., 1983 Glick et al., 1987 Lake et al.,... 

The mineralocorticoid effects of licorice are well documented see Human pharmacological studies) (Stewart et al. 1987). Licorice may cause reversible potassium depletion and sodium retention when consumed in therapeutic dosages over a prolonged period (Bensky et al. 2004 Bradley 1992 Martindale and Reynolds 1996). Most cases of adverse events associated with licorice have been reported in persons consuming excessive amounts of licorice candies. Overdoses of licorice have been associated with temporary paralysis, loss of vision, sodium and fluid retention, hypertension, and decreased serum levels of aldosterone. Licorice-related potassium depletion has resulted in symptoms such as tachycardia, rhabdomyolysis, myopathy, and hypokalemic paralysis. These effects are attributed primarily to the action of the compound glycyrrhizin (Isbrucker and Burdock 2006). Preparations of licorice without this compound, deglycyrrhizinated licorice (DGL), are available. 

Adverse events, primarily cardiovascular in nature, have been reported in persons consuming "energy drinks" and weight-loss supplements that contain guarana and multiple other botanical extracts, added caffeine, and other stimulant compounds (Pittler et al. 2005). 

Currently, there are no mandated US federal guidelines to report adverse events or consumer health complaints associated with the use of dietary supplements. MedWatch reporting is voluntary. In 2004, the Life Sciences Research Office published a report. Recommendations for Adverse Event Monitoring Programs for Dietary Supplements. 

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