effects side ocular induced-drug of registry National  • T5 PA  R

Send to:

Frederick W. Fraunfelder, Director

National Registry of Drug-Induced Ocular Side Effects Casey Eye Institute

Oregon Health Sciences University 3375 S.W. Terwilliger Blvd. Portland, Oregon 97239-4197 http://www.eyedrugregistry.com E-mail: eyedrug@ohsu.edu

References and Further Reading

Bate A, Lindquist M, Edwards IR, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol 54: 315–321, 1998.

Bate A, Orre R, Lindquist M, et al. Explanation of data mining methods. BMJ website 2001; http://www.bmj.com/cgi/content/full/322/7296/1207/ DC1.html.

Bate A, Lindquist M, Edwards IR, et al. A data mining approach for signal detection and analysis. Drug Saf 25: 393–397, 2002.

Bate A, Lindquist M, Orre R, et al. Data mining analyses of pharmacovigilance signals in relation to relevant comparison drugs. Eur J Clin Pharmacol 58: 483–490, 2002.

Coulter DM, Bate A, Meyboom RHB, et al. Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: a data mining study. BMJ 322: 1207–1209, 2001.

Lindquist M, Stahl M, Bate A, et al. A retrospective evaluation of a data mining approach to aid finding new adverse drug reaction signals in the WHO international database. Drug Saf 23: 533–542, 2000.

Orre R, Lansener A, Bate A, et al. Bayesian neural networks with confidence estimations applied to data mining. Comput Stat Data Anal 34: 473–493, 2000.

Spigset O, Hagg S, Bate A. Hepatic injury and pancreatitis during treatment with serotonin reuptake inhibitors: data from the World Health Organization (WHO) database of adverse drug reactions. Int Clin Psychopharmacol 18: 157–161, 2003.

Van Puijenbroek EM, Bate A, Leufkens HGM, et al. A comparison of ­measures of disproportionality for signal detection in spontaneous ­reporting systems for adverse drug reaction. Pharmacoepidemiol Drug Saf 11: 3–10, 2002.

Dietary supplements are prevalent worldwide and play a significant role in the treatment of human disease. In the USA, allopathic physicians are at the early stage of learning how to treat patients with natural remedies and other forms of alternative medicine. Elsewhere, however, alternative remedies have been embraced more fully. In Germany, for example, the German Federal Health Agency created a Commission E, which has allowed for a more sophisticated approach to assessing the efficacy and safety of dietary supplements and herbal medicines, and health insurance in Germany frequently covers costs for doctor-prescribed herbal remedies. Approximately 50% of the population in the USA takes herbal products compared to 70% of the population of Germany. From published studies, only half of patients report supplement use to their physician as many consider naturally occurring products to be safe (Eisenberg 1998).

Dietary supplements represent a $US60 billion industry worldwide. While strong arguments can be made by the natural product industry that the majority of dietary supplements are safe, especially when taken in proper doses, severe toxic reactions can and do occur. Physicians and patients need to be aware of these side effects, especially as many herbal products interact with prescription medications (Coxeter et al 2004).

Frequently, ophthalmologists are the first to identify dietary supplement adverse reactions as loss of vision and eye side effects can be the first symptoms noted by patients (Fraunfelder 2004, 2005a). Systemic adverse events may not be recognized until much later, i.e. urinary tract cancer from aristolochia fangi (Nortier 2000) or death from chronic liver damage from comfrey (symphytum officinale) (Anderson and McLean 1989).

Regulatory Issues and

Classification

Regulation and classification of dietary supplements is a confusing subject and standards vary from country to country. In the USA it is estimated that dietary supplements represent a $20 billion industry. The US Dietary Supplement Health Education Act of 1994 (DSHEA) allows herbal product companies to make ‘structure or function’ claims and disallows ‘disease’ claims. In other words, herb A can claim to maintain healthy eyes but herb A cannot make a claim that it treats glaucoma. While this seems straightforward, the FDA is unable to keep up with erroneous and sometimes illegal disease treatment claims made by the dietary supplement industry. Unlike prescription drugs, which fall under the US Food, Drug, and Cosmetic Act, dietary supplements do not have to prove pre-marketing safety or efficacy and only need to conform to the DSHEA to be legal. This creates a particularly difficult situation in which the FDA must prove a medication is dangerous after it is marketed before it can withdraw it from the market. For example, ephedra was withdrawn after causing adverse cardiovascular effects and death (Ling 2004). Even with the DSHEA, many supplements

Table 6.1 – Dietary Supplements Used to Treat Eye ­isease

Table 6.2 – Ocular Side Effects Associated With Dietary

Supplements

are marketed illegally, as evidenced by a study in the Journal of the American Medical Association, which researched the marketing practices of dietary supplement companies. This study showed that 55% of retailers make illegal disease claims of the treatment, prevention, diagnosis and cure of specific diseases through self treatment with various herbal medicines and nutritional supplements (Morris and Avorn 2003).

Classification of dietary supplements is also a difficult issue. In many countries, including the USA, different parts of the plant are harvested, and the collection and extraction of ingredients vary from company to company. Is the root, the flower, the stem or the seed being used for therapeutic benefit? How much of a herb is in the marketed product? Ginseng was evaluated by the American Botanical Council in 2001 and it was found that only 52% of marketed ginseng products actually contained any ginseng (Dharmananda 2002). Because of issues such as these, the World Health Organization (WHO) has published guidelines on cultivating, collecting, classification, quality control, storage, labeling, distribution and post-marketing surveillance of herbal medicines, which if adhered to worldwide would simplify the classification process (WHO Guidelines 2004).

The following herbal medicines and dietary supplements are described in this book as the ocular side effects are significant and well-documented: Canthaxanthine, Chamomile, Chrysanthenemum, Datura, Echinacea purpurea, Ginkgo biloba, licorice, niacin, vitamin A and vitamin D (Fraunfelder 2004, 2005a). There are many other herbs and supplements used to treat eye disease and many are associated with adverse ocular events; these are summarized in Tables 6.1 and 6.2.

References And Further Reading

Anderson PC, McLean AEM. Comfrey and liver damage. Hum Toxicol 8: 68–69, 1989.

Coxeter PD, et al. Herb-drug interactions: An evidence based approach. Curr Med Chem 11: 1513–1525, 2004.

Dharmananda S. The nature of ginseng: traditional use, modern research and the question of dosage. Herbal Gram 54: 34–51, 2002.

Eisenberg DM. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 289(18): 1569–1575, 1998.

Fraunfelder FW. Ocular side effects from herbal medicines and nutritional supplements. Am J Ophthalmol 138(4): 639–647, 2004.

Fraunfelder FW. The science and marketing of dietary supplements. Am J Ophthalmol 140: 302–304, 2005a.

Fraunfelder FW. Ocular side effects associated with dietary supplements and herbal medicines. Drugs Today 41: 537–545, 2005b.

Ling AM. FDA to ban sales of dietary supplements containing ephedra. J Law Med Ethics 32(1): 184–186, 2004.

Morris CA, Avorn J. Internet marketing of herbal products. JAMA 290(11): 1505–1509, 2003.

Nortier JL. Urothelial carcinoma associated with the use of a Chinese herb. N Engl J Med 342: 1686–1692, 2000.

WHO Guidelines on Good Agricultural and Collection Practices for Medicinal Plants. Marketing and Dissemination. World Health Organization, Geneva, Switzerland, 2004.

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