FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 343:1826-1832 December 21, 2000 Number 25 Next

	Full Text PDF Editorial by Fleming, G. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case–control study.

Methods Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient.

Results There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants.

Conclusions The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.

Source Information

From the Departments of Internal Medicine (W.N.K., C.M.V., R.I.H.), Neurology (L.M.B.), and Epidemiology and Public Health (L.M.B., R.I.H.), Yale University School of Medicine, New Haven, Conn.; the Department of Neurology, University of Cincinnati, Cincinnati (J.P.B.); the Department of Neurology, Mayo Clinic, Jacksonville, Fla. (T.B.); the Department of Neurology, Brown University School of Medicine, Providence, R.I. (E.F., J.L.W.); and the Department of Neurology and School of Public Health, University of Texas, Houston (L.B.M.).

Address reprint requests to Dr. Kernan at the Department of Medicine, Yale University School of Medicine, P.O. Box 208025, New Haven, CT 06520-8025.

Full Text of this Article

This article has been cited by other articles:

• Roach, E. S., Golomb, M. R., Adams, R., Biller, J., Daniels, S., deVeber, G., Ferriero, D., Jones, B. V., Kirkham, F. J., Scott, R. M., Smith, E. R. (2008). Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 39: 2644-2691 [Abstract] [Full Text]  
• Hallas, J., Bjerrum, L., Stovring, H., Andersen, M. (2008). Use of a Prescribed Ephedrine/Caffeine Combination and the Risk of Serious Cardiovascular Events: A Registry-based Case-Crossover Study. Am J Epidemiol 0: kwn191v1-kwn191 [Abstract] [Full Text]  
• Mikaeloff, Y., Caridade, G., Rossier, M., Suissa, S., Tardieu, M. (2007). Hepatitis B Vaccination and the Risk of Childhood-Onset Multiple Sclerosis. Arch Pediatr Adolesc Med 161: 1176-1182 [Abstract] [Full Text]  
• Winterstein, A. G., Gerhard, T., Shuster, J., Johnson, M., Zito, J. M., Saidi, A. (2007). Cardiac Safety of Central Nervous System Stimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder. Pediatrics 120: e1494-e1501 [Abstract] [Full Text]  
• Huizinga, M. M. (2007). Weight-Loss Pharmacotherapy: A Brief Review. Clin. Diabetes 25: 135-140 [Abstract] [Full Text]  
• Azzaro, A. J., VanDenBerg, C. M., Ziemniak, J., Kemper, E. M., Blob, L. F., Campbell, B. J. (2007). Evaluation of the Potential for Pharmacodynamic and Pharmacokinetic Drug Interactions Between Selegiline Transdermal System and Two Sympathomimetic Agents (Pseudoephedrine and Phenylpropanolamine) in Healthy Volunteers. J Clin Pharmacol 47: 978-990 [Abstract] [Full Text]  
• Domingue, J. N., Yoon, B .-W., Park, B .J., Bae, H .J., Hong, K .S. (2007). PHENYLPROPANOLAMINE CONTAINED IN COLD REMEDIES AND RISK OF HEMORRHAGIC STROKE. Neurology 69: 320-321 [Full Text]  
• Bray, G. A., Greenway, F. L. (2007). Pharmacological Treatment of the Overweight Patient. Pharmacol. Rev. 59: 151-184 [Full Text]  
• Westover, A. N., McBride, S., Haley, R. W. (2007). Stroke in Young Adults Who Abuse Amphetamines or Cocaine: A Population-Based Study of Hospitalized Patients. Arch Gen Psychiatry 64: 495-502 [Abstract] [Full Text]  
• Hatton, R. C, Winterstein, A. G, McKelvey, R. P, Shuster, J., Hendeles, L. (2007). Efficacy and Safety of Oral Phenylephrine: Systematic Review and Meta-Analysis. The Annals of Pharmacotherapy 41: 381-390 [Abstract] [Full Text]  
• Yoon, B. W., Bae, H. J., Hong, K. S., Lee, S. M., Park, B. J., Yu, K. H., Han, M. K., Lee, Y. S., Chung, D. K., Park, J. M., Jeong, S. W., Lee, B. C., Cho, K. H., Kim, J. S., Lee, S. H., Yoo, K. M., for the Acute Brain Bleeding Analysis (ABBA) Study, (2007). Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke. Neurology 68: 146-149 [Abstract] [Full Text]  
• Cohen-Kerem, R., Ratnapalan, S., Djulus, J., Duan, X., Chandra, R. V., Ito, S. (2006). The Attitude of Physicians Toward Cold Remedies for Upper Respiratory Infection in Infants and Children: A Questionnaire Survey. CLIN PEDIATR 45: 828-834 [Abstract]  
• Schubiner, H., Hassunizadeh, B., Kaczynski, R. (2006). A controlled study of autonomic nervous system function in adults with attention-deficit/hyperactivity disorder treated with stimulant medications: results of a pilot study.. J Atten Disord 10: 205-211 [Abstract]  
• Nissen, S. E. (2006). ADHD Drugs and Cardiovascular Risk. NEJM 354: 1445-1448 [Full Text]  
• Campos, P., Saguy, A., Ernsberger, P., Oliver, E., Gaesser, G. (2006). The epidemiology of overweight and obesity: public health crisis or moral panic?. Int J Epidemiol 35: 55-60 [Full Text]  
• Lexchin, J. (2006). Is there still a role for spontaneous reporting of adverse drug reactions?. CMAJ 174: 191-192 [Full Text]  
• Crandell, J. M., Ware, W. A. (2005). Cardiac Toxicity From Phenylpropanolamine Overdose in a Dog. Journal of the American Animal Hospital Association 41: 413-420 [Abstract] [Full Text]  
• Feldmann, E., Broderick, J. P., Kernan, W. N., Viscoli, C. M., Brass, L. M., Brott, T., Morgenstern, L. B., Wilterdink, J. L., Horwitz, R. I. (2005). Major Risk Factors for Intracerebral Hemorrhage in the Young Are Modifiable. Stroke 36: 1881-1885 [Abstract] [Full Text]  
• Shekelle, P. G., Morton, S. C., Suttorp, M. J., Buscemi, N., Friesen, C. (2005). Challenges in Systematic Reviews of Complementary and Alternative Medicine Topics. ANN INTERN MED 142: 1042-1047 [Abstract] [Full Text]  
• Flavahan, N. A. (2005). Phenylpropanolamine Constricts Mouse and Human Blood Vessels by Preferentially Activating {alpha}2-Adrenoceptors. J. Pharmacol. Exp. Ther. 313: 432-439 [Abstract] [Full Text]  
• Shibao, C., Gamboa, A., Diedrich, A., Biaggioni, I. (2005). Management of Hypertension in the Setting of Autonomic Failure: A Pathophysiological Approach. Hypertension 45: 469-476 [Abstract] [Full Text]  
• Enevoldson, T P (2004). Recreational drugs and their neurological consequences. J. Neurol. Neurosurg. Psychiatry 75: iii9-iii15 [Full Text]  
• Norris, S. L., Zhang, X., Avenell, A., Gregg, E., Schmid, C. H., Kim, C., Lau, J. (2004). Efficacy of Pharmacotherapy for Weight Loss in Adults With Type 2 Diabetes Mellitus: A Meta-analysis. Arch Intern Med 164: 1395-1404 [Abstract] [Full Text]  
• Barst, R J, Abenhaim, L (2004). Fatal pulmonary arterial hypertension associated with phenylpropanolamine exposure. Heart 90: e42-e42 [Abstract] [Full Text]  
• Dillon, P. F., Root-Bernstein, R. S., Lieder, C. M. (2004). Antioxidant-independent ascorbate enhancement of catecholamine-induced contractions of vascular smooth muscle. Am. J. Physiol. Heart Circ. Physiol. 286: H2353-H2360 [Abstract] [Full Text]  
• Jordan, J., Shannon, J. R., Diedrich, A., Black, B., Robertson, D., Biaggioni, I. (2004). Water Potentiates the Pressor Effect of Ephedra Alkaloids. Circulation 109: 1823-1825 [Abstract] [Full Text]  
• La Puma, J., Szapary, P., Maki, K. C. (2004). Physicians' Personal Intake and Prescription of Weight Loss Products: Are We Practicing What We Preach?. Arch Intern Med 164: 806-807 [Full Text]  
• Roberts, S. B, Krupa Das, S., Saltzman, E. (2004). Energy expenditure in obesity. Am. J. Clin. Nutr. 79: 181-182 [Full Text]  
• Kurth, T., Cantu, C., Arauz, A., Murillo-Bonilla, L., Barinagarrementeria, F. (2003). Over-the-Counter Cough and Cold Medication Use and Risk of Stroke * Response. Stroke 34 : e234-e235 [Full Text]  
• Smith, M. A., Risser, J. M.H., Lisabeth, L. D., Moye, L. A., Morgenstern, L. B. (2003). Access to Care, Acculturation, and Risk Factors for Stroke in Mexican Americans: The Brain Attack Surveillance in Corpus Christi (BASIC) Project. Stroke 34: 2671-2675 [Abstract] [Full Text]  
• Rothman, R. B., Vu, N., Partilla, J. S., Roth, B. L., Hufeisen, S. J., Compton-Toth, B. A., Birkes, J., Young, R., Glennon, R. A. (2003). In Vitro Characterization of Ephedrine-Related Stereoisomers at Biogenic Amine Transporters and the Receptorome Reveals Selective Actions as Norepinephrine Transporter Substrates. J. Pharmacol. Exp. Ther. 307: 138-145 [Abstract] [Full Text]  
• Cantu, C., Arauz, A., Murillo-Bonilla, L. M., Lopez, M., Barinagarrementeria, F. (2003). Stroke Associated With Sympathomimetics Contained in Over-the-Counter Cough and Cold Drugs. Stroke 34: 1667-1672 [Abstract] [Full Text]  
• Brust, J. C.M. (2003). Editorial Comment--Over-the-Counter Cold Remedies and Stroke. Stroke 34: 1673-1673 [Full Text]  
• Weigle, D. S. (2003). Pharmacological Therapy of Obesity: Past, Present, and Future. J. Clin. Endocrinol. Metab. 88: 2462-2469 [Full Text]  
• Broderick, J. P., Viscoli, C. M., Brott, T., Kernan, W. N., Brass, L. M., Feldmann, E., Morgenstern, L. B., Wilterdink, J. L., Horwitz, R. I. (2003). Major Risk Factors for Aneurysmal Subarachnoid Hemorrhage in the Young Are Modifiable. Stroke 34: 1375-1381 [Abstract] [Full Text]  
• Morgenstern, L.B., Viscoli, C.M., Kernan, W.N., Brass, L.M., Broderick, J.P., Feldmann, E., Wilterdink, J.L., Brott, T., Horwitz, R.I. (2003). Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurology 60: 132-135 [Abstract] [Full Text]  
• Corns, C, Metcalfe, K (2002). Risks associated with herbal slimming remedies. The Journal of the Royal Society for the Promotion of Health 122: 213-219 [Abstract]  
• Yanovski, S. Z., Yanovski, J. A. (2002). Obesity. NEJM 346: 591-602 [Full Text]  
• Werning, J. W., Preston, T. W., Khuder, S. (2002). Physician Specialty Is Associated With Differences in the Evaluation and Management of Acute Bacterial Rhinosinusitis. Arch Otolaryngol Head Neck Surg 128: 123-130 [Abstract] [Full Text]  
• De Foa, L. (2002). Don't be so quick to ban medications. CMAJ 166: 13-13 [Full Text]  
• Arauz-Pacheco, C., Parrott, M. A., Raskin, P. (2002). The Treatment of Hypertension in Adult Patients With Diabetes. Diabetes Care 25: 134-147 [Full Text]  
• La Grenade, L., Graham, D. J., Nourjah, P. (2001). Underreporting of Hemorrhagic Stroke Associated With Phenylpropanolamine. JAMA 286: 3081-3081 [Full Text]  
• Tofovic, S. P., Dubey, R. K., Jackson, E. K. (2001). 2-Hydroxyestradiol Attenuates the Development of Obesity, the Metabolic Syndrome, and Vascular and Renal Dysfunction in Obese ZSF1 Rats. J. Pharmacol. Exp. Ther. 299: 973-977 [Abstract] [Full Text]  
• Clark, D., Layton, D., Shakir, S. A W (2001). Monitoring the safety of over the counter drugs. BMJ 323: 706-707 [Full Text]  
• Gunn, V. L., Taha, S. H., Liebelt, E. L., Serwint, J. R. (2001). Toxicity of Over-the-Counter Cough and Cold Medications. Pediatrics 108: e52-52 [Abstract] [Full Text]  
• Blanck, H. M., Khan, L. K., Serdula, M. K. (2001). Use of Nonprescription Weight Loss Products: Results From a Multistate Survey. JAMA 286: 930-935 [Abstract] [Full Text]  
• Ernst, M. E., Hartz, A., Wolowich, W. R., Casavant, M. J., Ekins, B. R., Kernan, W. N., Viscoli, C. M., Brass, L. M., Horwitz, R. I., Fleming, G. A. (2001). Phenylpropanolamine and Hemorrhagic Stroke. NEJM 344: 1094-1095 [Full Text]  
• Hutchins, G. M., Traub, S. J., Hoyek, W., Hoffman, R. S., Haller, C. A., Benowitz, N. L. (2001). Dietary Supplements Containing Ephedra Alkaloids. NEJM 344: 1095-1097 [Full Text]  
• (2001). Risk for Hemorrhagic Stroke with Phenylpropanolamine. JWatch Neurology 2001: 4-4 [Full Text]  
• (2001). Phenylpropanolamine and hemorrhagic stroke in women. CMAJ 164: 684-684 [Full Text]  
• Hamedani, A. G., Wells, C. K., Brass, L. M., Kernan, W. N., Viscoli, C. M., Maraire, J. N., Awad, I. A., Horwitz, R. I. (2001). A Quality-of-Life Instrument for Young Hemorrhagic Stroke Patients. Stroke 32: 687-695 [Abstract] [Full Text]  
• (2001). Phenylpropanolamine and the Risk for Hemorrhagic Stroke in Women. JWatch Psychiatry 2001: 15-15 [Full Text]  
• (2000). Risks with Phenylpropanolamine and Ephedra Alkaloids. JWatch General 2000: 1-1 [Full Text]  
• Fleming, G. A. (2000). The FDA, Regulation, and the Risk of Stroke. NEJM 343: 1886-1887 [Full Text]  
• (2000). Phenylpropanolamine and the Risk for Hemorrhagic Stroke in Women. JWatch Women's Health 2000: 1-1 [Full Text]  
• Jordan, J., Tank, J., Shannon, J. R., Diedrich, A., Lipp, A., Schroder, C., Arnold, G., Sharma, A. M., Biaggioni, I., Robertson, D., Luft, F. C. (2002). Baroreflex Buffering and Susceptibility to Vasoactive Drugs. Circulation 105: 1459-1464 [Abstract] [Full Text]