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Ipecac syrup abuse, morbidity, and mortality: Isn’t it time to repeal its over-the-counter status?
Journal of Adolescent Health 37 (2005) 256 –260
Review article
Ipecac syrup abuse, morbidity, and mortality: Isn’t it time to repeal its over-the-counter status? Tomas J. Silber, M.D., M.A.S.S.a,b,* b
a Division of Adolescent Medicine, Children’s National Medical Center, Washington, D.C. George Washington University School of Medicine and Health Sciences, Washington, D.C. Manuscript received April 26, 2004; manuscript accepted August 26, 2004
Abstract
Purpose: To review and address the abuse of ipecac, describing its epidemiology, toxicity, clinical characteristics, and laboratory assessment. Methods: A Medline search (1980 –2003) for Ipecac abuse and Ipecac toxicity, n ⫽ 34. Results: Ipecac abuse occurs predominantly among adolescent and young adult females who are either experimenting with purging or have an eating disorder. Psychiatric comorbidity is common. Death can occur and is usually of cardiac origin. Morbidity includes myocarditis with arrhythmias, myositis, gastroesophageal pathology, including Mallory Weiss tears, diarrhea, and metabolic abnormalities (alkalosis, hypokalemia, dehydration). The injuries can reverse with cessation of ipecac use. A high index of suspicion is needed for early detection. Classic findings are abnormal EKG and echocardiography and/or elevation of muscle enzymes (CPK, adolase). Emetine, the alkaloid in ipecac, can be confirmed in serum, urine, and tissue by high performance liquid chromatography. Conclusions: Ipecac abuse is dangerous, even deadly. However, if abuse is discontinued, cardiac and muscle damage tends to reverse. Were ipecac syrup to remain an over- the-counter medication, or become a prescription medication, more stringent warning labels ought to be included and further education be provided about its toxicity and potential for abuse. Removing ipecac from the over-the-counter category would best eliminate its potential for abuse. © 2005 Society for Adolescent Medicine. All rights reserved.
Keywords:
Eating disorders; Myositis; Ipecac abuse; Ipecac toxicity; Cardiomyopathy
Ipecac syrup is prepared from powdered ipecac, which is obtained from the plant Cephaelis ipecacuanha. The syrup contains two active alkaloids, cephaeline and emetine, which induce emesis acting locally on gastric mucosal receptors and centrally at the chemoreceptor trigger zone in the brainstem. Ipecac syrup’s proposed indication is “for emergency use to cause vomiting in poisoning” [1]. Used to treat accidental poisoning, a dose of 15 mL induces vomiting within 20 minutes. If emesis is not induced with a second dose, it has been recommended to
*Address correspondence to: Tomas Silber, M.D., Adolescent Medicine, Children’s National Medical Center, 111 Michigan Avenue, NW Washington, D.C. 20010-2970. E-mail address: [email protected]
recover it by gastric lavage because it “may cause serious poisoning” [2]. Ipecac syrup has been available as an over-the-counter (OTC) drug product since October 27, 1965 [3]. Recently reports in the toxicology literature and some medical societies have increasingly questioned whether there is sufficient evidence to justify its use [4 –18]. These doubts about the usefulness of ipecac syrup in the management of poisoned patients, coupled with the possibility of morbidity and mortality associated with its use and abuse, prompted the FDA’s decision to re-evaluate the current non-prescription status of ipecac syrup [19]. On June 12, 2003, the FDA Center for Drug Evaluation and Research convened a Nonprescription Drugs Advisory Committee meeting in Bethesda, Maryland, to review ipe-
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T.J. Silber / Journal of Adolescent Health 37 (2005) 256 –260
cac syrup’s OTC status. The issues covered were its role in gastrointestinal decontamination, the risk benefit ratio, the role in the treatment for populations with limited access to emergency medical treatment, alternative therapies, and abuse of ipecac syrup. The latter, on which the author of this article testified, will be the focus of this article [20]. The FDA panel that analyzed the existing data and listened to expert testimony recommended that the OTC status for ipecac be revoked [21]. What follows is, therefore, both a literature review and an advocacy paper. It will address the abuse of ipecac, describing its epidemiology, toxicity, clinical characteristics, and laboratory assessment. Methods A Medline search (1980 –2003, n ⫽ 34) was done for ipecac abuse, epidemiology, toxicity, morbidity, and mortality. Ipecac abuse was defined as the repeated use of the syrup for the sole purpose of self-inducing emesis as a method of weight control [20]. Other forms of ipecac poisoning were excluded from this definition, such as the repeated administration of ipecac syrup by a parent to a child in order to produce a factitious illness (Munchausen by proxy) [22– 32]. The latter is a condition that differs from ipecac abuse in that it affects very young children, entailing a criminal act of poisoning and child abuse. However, since Munchausen by proxy shares with ipecac abuse its morbidity and mortality, data relating to toxicity, physiopathology, and medical complications suffered by its victims will be incorporated in this review. Results Epidemiology Self-induced vomiting occurs predominantly among adolescent females and young adult women [33]. It can take place in the context of episodes of adolescent experimentation or be firmly entrenched as part of a well developed eating disorder [34]. Although it has been more frequently described in patients with Bulimia Nervosa, self-induced emesis also takes place in a large number of patients with Anorexia Nervosa (binge-purge subtype), as well as in those affected by eating disorder not otherwise specified [35]. The practice is secret and surreptitious, so it is hard to detect. The epidemiology of ipecac abuse is, therefore, difficult to ascertain [33]. Nevertheless, it is possible to obtain an approximation by looking at population studies of both eating disorders and ipecac abuse. The lifetime prevalence of Anorexia Nervosa ranges between 0.1 to 1% [36 –39] and between 8 to 41% of individuals with Anorexia Nervosa will develop Bulimia Nervosa [40 – 46]. Moreover, the lifetime prevalence of the latter is estimated to be between 1 and 3% [46 – 48]. Data on ipecac abuse among patients with eating disorders are scant: two studies have reported on the
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extent of ipecac abuse in patients with eating disorders. In one, of 851 patients in an eating disorders clinic, 7.8% had used ipecac (4.7% intermittently and 3.1% chronically) [49]. In the other, also in an eating disorders clinic, of 622 patients 3.8% of the women had used ipecac [50]. Clinical experience suggests that ipecac abuse has continued unabated. Extrapolating the above percentages to the number of adolescents and young women with eating disorders, the numbers of ipecac abusers at any given time may be ranging in the thousands [20]. Toxicity Ipecac is not an innocuous substance. Historical data have long pointed towards ipecac toxicity, both for emetine treatment of amebiasis or for its emetic purpose [51]. Ipecac makes approximately 85% of people vomit after one dose and 95% after two doses. Onset of emesis is within 20 –30 minutes. Patients given ipecac absorb its component alkaloids. Emetine is excreted by the kidneys and can be detected in the urine 40 to 60 days following the administration of a single dose [52]. It is noteworthy that the ipecac labeling does not contain the maximum total dose or the maximum number of times the dose can be repeated. Ipecac has been associated with severe retching and prolonged and repeated emesis. Ipecac toxicity includes abdominal cramping, Mallory-Weiss tears, skeletal muscle weakness, mild tremor, and convulsions [28,30 –32,53– 60]. Cardiac effects include tachycardia, hypotension, dyspnea, precordial pain, and arrhythmias [24,29,59,60]. Pneumomediastinum and retroneuromoperitoneum have also been described [61]. The most severe injuries associated with the repeated and chronic use of Ipecac are myositis [56 – 60, 63,64] and myocardial damage [24,27,29,62]. Death may result from arrhythmia or heart failure [63– 68]. The ultrastructural pathology in emetine induced myopathy is characterized by severe disruption of sarcomeres. The lesion spectrum ranges from “Z band streaming” to the formation of cytoplasmic bodies, including abnormalities of the sarcotubular system [62]. The classic cardiac lesion is a cardiomyopathy, which can result in an enlarged heart. Electron microscopy of the myocardium may reveal zones of myofibrillar lysis, fragmented fibers, and irregular alignment of clumps of Z-bands [29]. If the abuse of ipecac ends, the muscular and cardiac lesions may be reversible [69,70]. Clinical characteristics, morbidity, and mortality Those patients with eating disorders who can easily selfinduce vomiting do not need to make use of ipecac. There is, however, a significant number of adolescents and young adults determined to purge who cannot self-induce emesis, or can do so only with great difficulty. It is the author’s experience that these are the young women who may be at high risk for experimentation with ipecac [20]. Many firsttime users discover that it induces severe vomiting, retch-
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ing, abdominal pain, and malaise and may not go on to abuse. Others will be willing to undertake repeating this ordeal and risk becoming abusers. Even a single episode of ipecac use can cause significant morbidity [54]. It is not uncommon for one girl to initiate another in its use. Ipecac has been promoted in “pro-anorexia” websites. Data on adverse events (AE) with ipecac are very limited because OTC products do not require submission of AE to the FDA. Nevertheless, a Post Marketing Safety Review by the Center for Drug Evaluation and Research by the FDA revealed 17 adverse event reports involving ipecac, including eight fatalities, half of them with documented abuse [68]. The ipecac abuser does so secretly and surreptitiously, often purchasing the syrup in different pharmacies. Symptoms initially may be nonspecific and underreported. The prominent symptoms of chronic use are intractable vomiting, diarrhea, hemorrhagic colitis, muscular weakness, cardiac failure, and arrhythmias [55– 68].Frequently users will be denying the seriousness of the symptomatology or will not see the connection between their use of ipecac and feeling sick. Some, who understand what is happening to them, may still lie about it, in their unshakable conviction that “I’d rather be dead than fat.” All these characteristics conspire against recognition of ipecac toxicity unless there is a high index of suspicion. Detection and diagnostic tests Suspicion of ipecac abuse is essential for its detection [71]. Frequent dieters, patients with abnormal weight loss, and patients with eating disorders should be the main suspects, as well as those with recurrent emesis or its laboratory indicators, hypokalemia and hypochloremic alkalosis. Adolescents and young adults with muscle weakness and cardiac symptoms of indeterminate origin should also be investigated [20]. Direct questioning may at times result in a candid admission of use or in “guilty hesitation.” Laboratory assessment is crucial and can give substantial information, such as marked elevations of the creatinine phosphokinase (CK), moderate increases in lactate dehydrogenase, and mild alterations of liver enzymes [59,60]. The ipecac alkaloid emetine can be detected in urine and serum by high pressure liquid chromatography, thin-layer chromatography, or with fluorescence and ultraviolet/diode array detection [52,72–74]. Ipecac alkaloids can be detected in urine several weeks after ingestion [75]. The cardiac evaluation may show an abnormal EKG with prolonged QTc interval, T wave flattening or inversion, and tachycardia [29]. Echocardiography may reveal ventricular dysfunction, reduced ejection fraction, and fractional shortening [70]. Electromyography and muscle biopsy show myopathy [57,62]. The presence of ipecac can be confirmed in biopsy or necropsy tissue by high performance liquid chromatography [72].
Discussion While syrup of ipecac has been available as OTC since 1965 to induce emesis for certain poisonings (21 CFR 201.308), its unexpected abuse has been described in the last twenty-odd years. The epidemiological data available are quite compelling [33,50]. A limitation of this information is that its main source stems from a somewhat biased sample, as it originates in specialized eating disorders clinics, rather than from a general population study [49,50]. It could be argued that since only the sickest patients attend these clinics, their data on the use of ipecac is much higher than what one would see in a non-patient population with eating disorders. On the other hand, one could equally argue that this information is the proverbial tip of the iceberg, and that the abuse of ipecac may be even higher among those who refuse to see a doctor or are taken care of by professionals who have not had sufficient training or experience in the field of eating disorders to become suspicious of ipecac abuse [20]. While admitting that there are currently no direct population studies of ipecac abuse, combining the available data with clinical experience suggests that ipecac abuse among female adolescents and young women must be considered a serious health issue [20]. Since the source of ipecac syrup is of course the legal over-the-counter purchase of syrup of ipecac, it is reasonable to postulate that if the purchase would require a prescription it would make ipecac abuse much harder to practice. If ipecac were removed from sales, the toxicity would end. Arguments relating to the ineffectiveness of syrup of ipecac have been made repeatedly, and the product is no longer used in Europe [16]. The American Academy of Pediatrics no longer recommends its storage at home nor its use for prevention of pediatric poisonings [18]. The FDA is currently looking at this issue. In a recent hearing, an advisory panel voted 6 to 4 that ipecac syrup should no longer be available over the counter [21]. It is even possible that, if taken out of the “over-the-counter” category, ipecac syrup may not qualify for the prescription track, in which case it would no longer be available [65]. Thus, ipecac abuse could end in the same way as death from tincture of ipecac ended when that preparation was removed from the market in 1975. Since it is unlikely, because of the time and high cost necessary for a pharmaceutical company to file a New Drug Application for marketing ipecac as a prescription drug, a decision to remove its OTC status would actually lead to “the demise of ipecac” [76]. On the other hand, were ipecac syrup to survive as an over-the-counter medication, or unexpectedly be approved as a prescription medication, it will become increasingly necessary to further educate health professionals, including pharmacists, about its toxicity and potential for abuse. Moreover, more stringent warning labels would need to be added (Table 1).
T.J. Silber / Journal of Adolescent Health 37 (2005) 256 –260 Table 1 Proposed warnings re. lpecac syrup abuse ● Use of ipecac to repeatedly self induce vomiting is hazardous to your health ● Repeated use of ipecac is poisonous and can induce muscle weakness and pain secondary to muscle destruction ● Ipecac toxicity from repeated use can lead to cardiac damage, arrhythmia and death ● If you are abusing or have abused ipecac, seek professional advice.
Conclusions Ipecac abuse is a secret and compulsive activity engaged predominantly by female adolescents and young women for the purpose of weight loss/weight control [20,33,49,50,71]. This review of the medical literature confirms that it may result in severe morbidity and mortality [22–32,53– 62]. Recently, the effectiveness and efficacy of ipecac syrup for the prevention of childhood poisoning has been questioned [5–18,20 – 65]. In the absence of convincing evidence favoring the use of ipecac for this purpose, it makes sense to remove ipecac from its over-the- counter status, as this would significantly reduce its potential for abuse. However, if ipecac syrup were allowed to continue its OTC status, or given approval as a prescription drug, more stringent warning labels ought to be included, and further education be provided regarding its potential abuse. Based on the evidence presented, all those who care for adolescents and young adults struggling with eating disorders would certainly urge the FDA to accept the recommendations of the Nonprescription Drugs Advisory Committee to revoke the OTC status of ipecac syrup [20,21]. This would give a new lease on life to those who are “hooked on the bulimic drug” and prevent new generations from entering this dangerous path. It is time to remove ipecac from its over-the-counter status. Acknowledgments Based on an invited testimony to the Center for Drug Evaluation and Research Office of Executive Programs, U.S. Food and Drug Administration, Bethesda, Maryland, June 12th, 2003 and a presentation from the podium to the International Conference on Eating Disorders, American Academy for Eating Disorders, April 29, 2004, Orlando, Florida. References [1] [2] [3] [4]
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Review article
Ipecac syrup abuse, morbidity, and mortality: Isn’t it time to repeal its over-the-counter status? Tomas J. Silber, M.D., M.A.S.S.a,b,* b
a Division of Adolescent Medicine, Children’s National Medical Center, Washington, D.C. George Washington University School of Medicine and Health Sciences, Washington, D.C. Manuscript received April 26, 2004; manuscript accepted August 26, 2004
Abstract
Purpose: To review and address the abuse of ipecac, describing its epidemiology, toxicity, clinical characteristics, and laboratory assessment. Methods: A Medline search (1980 –2003) for Ipecac abuse and Ipecac toxicity, n ⫽ 34. Results: Ipecac abuse occurs predominantly among adolescent and young adult females who are either experimenting with purging or have an eating disorder. Psychiatric comorbidity is common. Death can occur and is usually of cardiac origin. Morbidity includes myocarditis with arrhythmias, myositis, gastroesophageal pathology, including Mallory Weiss tears, diarrhea, and metabolic abnormalities (alkalosis, hypokalemia, dehydration). The injuries can reverse with cessation of ipecac use. A high index of suspicion is needed for early detection. Classic findings are abnormal EKG and echocardiography and/or elevation of muscle enzymes (CPK, adolase). Emetine, the alkaloid in ipecac, can be confirmed in serum, urine, and tissue by high performance liquid chromatography. Conclusions: Ipecac abuse is dangerous, even deadly. However, if abuse is discontinued, cardiac and muscle damage tends to reverse. Were ipecac syrup to remain an over- the-counter medication, or become a prescription medication, more stringent warning labels ought to be included and further education be provided about its toxicity and potential for abuse. Removing ipecac from the over-the-counter category would best eliminate its potential for abuse. © 2005 Society for Adolescent Medicine. All rights reserved.
Keywords:
Eating disorders; Myositis; Ipecac abuse; Ipecac toxicity; Cardiomyopathy
Ipecac syrup is prepared from powdered ipecac, which is obtained from the plant Cephaelis ipecacuanha. The syrup contains two active alkaloids, cephaeline and emetine, which induce emesis acting locally on gastric mucosal receptors and centrally at the chemoreceptor trigger zone in the brainstem. Ipecac syrup’s proposed indication is “for emergency use to cause vomiting in poisoning” [1]. Used to treat accidental poisoning, a dose of 15 mL induces vomiting within 20 minutes. If emesis is not induced with a second dose, it has been recommended to
*Address correspondence to: Tomas Silber, M.D., Adolescent Medicine, Children’s National Medical Center, 111 Michigan Avenue, NW Washington, D.C. 20010-2970. E-mail address: [email protected]
recover it by gastric lavage because it “may cause serious poisoning” [2]. Ipecac syrup has been available as an over-the-counter (OTC) drug product since October 27, 1965 [3]. Recently reports in the toxicology literature and some medical societies have increasingly questioned whether there is sufficient evidence to justify its use [4 –18]. These doubts about the usefulness of ipecac syrup in the management of poisoned patients, coupled with the possibility of morbidity and mortality associated with its use and abuse, prompted the FDA’s decision to re-evaluate the current non-prescription status of ipecac syrup [19]. On June 12, 2003, the FDA Center for Drug Evaluation and Research convened a Nonprescription Drugs Advisory Committee meeting in Bethesda, Maryland, to review ipe-
1054-139X/05/$ – see front matter © 2005 Society for Adolescent Medicine. All rights reserved. doi:10.1016/j.jadohealth.2004.08.022
T.J. Silber / Journal of Adolescent Health 37 (2005) 256 –260
cac syrup’s OTC status. The issues covered were its role in gastrointestinal decontamination, the risk benefit ratio, the role in the treatment for populations with limited access to emergency medical treatment, alternative therapies, and abuse of ipecac syrup. The latter, on which the author of this article testified, will be the focus of this article [20]. The FDA panel that analyzed the existing data and listened to expert testimony recommended that the OTC status for ipecac be revoked [21]. What follows is, therefore, both a literature review and an advocacy paper. It will address the abuse of ipecac, describing its epidemiology, toxicity, clinical characteristics, and laboratory assessment. Methods A Medline search (1980 –2003, n ⫽ 34) was done for ipecac abuse, epidemiology, toxicity, morbidity, and mortality. Ipecac abuse was defined as the repeated use of the syrup for the sole purpose of self-inducing emesis as a method of weight control [20]. Other forms of ipecac poisoning were excluded from this definition, such as the repeated administration of ipecac syrup by a parent to a child in order to produce a factitious illness (Munchausen by proxy) [22– 32]. The latter is a condition that differs from ipecac abuse in that it affects very young children, entailing a criminal act of poisoning and child abuse. However, since Munchausen by proxy shares with ipecac abuse its morbidity and mortality, data relating to toxicity, physiopathology, and medical complications suffered by its victims will be incorporated in this review. Results Epidemiology Self-induced vomiting occurs predominantly among adolescent females and young adult women [33]. It can take place in the context of episodes of adolescent experimentation or be firmly entrenched as part of a well developed eating disorder [34]. Although it has been more frequently described in patients with Bulimia Nervosa, self-induced emesis also takes place in a large number of patients with Anorexia Nervosa (binge-purge subtype), as well as in those affected by eating disorder not otherwise specified [35]. The practice is secret and surreptitious, so it is hard to detect. The epidemiology of ipecac abuse is, therefore, difficult to ascertain [33]. Nevertheless, it is possible to obtain an approximation by looking at population studies of both eating disorders and ipecac abuse. The lifetime prevalence of Anorexia Nervosa ranges between 0.1 to 1% [36 –39] and between 8 to 41% of individuals with Anorexia Nervosa will develop Bulimia Nervosa [40 – 46]. Moreover, the lifetime prevalence of the latter is estimated to be between 1 and 3% [46 – 48]. Data on ipecac abuse among patients with eating disorders are scant: two studies have reported on the
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extent of ipecac abuse in patients with eating disorders. In one, of 851 patients in an eating disorders clinic, 7.8% had used ipecac (4.7% intermittently and 3.1% chronically) [49]. In the other, also in an eating disorders clinic, of 622 patients 3.8% of the women had used ipecac [50]. Clinical experience suggests that ipecac abuse has continued unabated. Extrapolating the above percentages to the number of adolescents and young women with eating disorders, the numbers of ipecac abusers at any given time may be ranging in the thousands [20]. Toxicity Ipecac is not an innocuous substance. Historical data have long pointed towards ipecac toxicity, both for emetine treatment of amebiasis or for its emetic purpose [51]. Ipecac makes approximately 85% of people vomit after one dose and 95% after two doses. Onset of emesis is within 20 –30 minutes. Patients given ipecac absorb its component alkaloids. Emetine is excreted by the kidneys and can be detected in the urine 40 to 60 days following the administration of a single dose [52]. It is noteworthy that the ipecac labeling does not contain the maximum total dose or the maximum number of times the dose can be repeated. Ipecac has been associated with severe retching and prolonged and repeated emesis. Ipecac toxicity includes abdominal cramping, Mallory-Weiss tears, skeletal muscle weakness, mild tremor, and convulsions [28,30 –32,53– 60]. Cardiac effects include tachycardia, hypotension, dyspnea, precordial pain, and arrhythmias [24,29,59,60]. Pneumomediastinum and retroneuromoperitoneum have also been described [61]. The most severe injuries associated with the repeated and chronic use of Ipecac are myositis [56 – 60, 63,64] and myocardial damage [24,27,29,62]. Death may result from arrhythmia or heart failure [63– 68]. The ultrastructural pathology in emetine induced myopathy is characterized by severe disruption of sarcomeres. The lesion spectrum ranges from “Z band streaming” to the formation of cytoplasmic bodies, including abnormalities of the sarcotubular system [62]. The classic cardiac lesion is a cardiomyopathy, which can result in an enlarged heart. Electron microscopy of the myocardium may reveal zones of myofibrillar lysis, fragmented fibers, and irregular alignment of clumps of Z-bands [29]. If the abuse of ipecac ends, the muscular and cardiac lesions may be reversible [69,70]. Clinical characteristics, morbidity, and mortality Those patients with eating disorders who can easily selfinduce vomiting do not need to make use of ipecac. There is, however, a significant number of adolescents and young adults determined to purge who cannot self-induce emesis, or can do so only with great difficulty. It is the author’s experience that these are the young women who may be at high risk for experimentation with ipecac [20]. Many firsttime users discover that it induces severe vomiting, retch-
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ing, abdominal pain, and malaise and may not go on to abuse. Others will be willing to undertake repeating this ordeal and risk becoming abusers. Even a single episode of ipecac use can cause significant morbidity [54]. It is not uncommon for one girl to initiate another in its use. Ipecac has been promoted in “pro-anorexia” websites. Data on adverse events (AE) with ipecac are very limited because OTC products do not require submission of AE to the FDA. Nevertheless, a Post Marketing Safety Review by the Center for Drug Evaluation and Research by the FDA revealed 17 adverse event reports involving ipecac, including eight fatalities, half of them with documented abuse [68]. The ipecac abuser does so secretly and surreptitiously, often purchasing the syrup in different pharmacies. Symptoms initially may be nonspecific and underreported. The prominent symptoms of chronic use are intractable vomiting, diarrhea, hemorrhagic colitis, muscular weakness, cardiac failure, and arrhythmias [55– 68].Frequently users will be denying the seriousness of the symptomatology or will not see the connection between their use of ipecac and feeling sick. Some, who understand what is happening to them, may still lie about it, in their unshakable conviction that “I’d rather be dead than fat.” All these characteristics conspire against recognition of ipecac toxicity unless there is a high index of suspicion. Detection and diagnostic tests Suspicion of ipecac abuse is essential for its detection [71]. Frequent dieters, patients with abnormal weight loss, and patients with eating disorders should be the main suspects, as well as those with recurrent emesis or its laboratory indicators, hypokalemia and hypochloremic alkalosis. Adolescents and young adults with muscle weakness and cardiac symptoms of indeterminate origin should also be investigated [20]. Direct questioning may at times result in a candid admission of use or in “guilty hesitation.” Laboratory assessment is crucial and can give substantial information, such as marked elevations of the creatinine phosphokinase (CK), moderate increases in lactate dehydrogenase, and mild alterations of liver enzymes [59,60]. The ipecac alkaloid emetine can be detected in urine and serum by high pressure liquid chromatography, thin-layer chromatography, or with fluorescence and ultraviolet/diode array detection [52,72–74]. Ipecac alkaloids can be detected in urine several weeks after ingestion [75]. The cardiac evaluation may show an abnormal EKG with prolonged QTc interval, T wave flattening or inversion, and tachycardia [29]. Echocardiography may reveal ventricular dysfunction, reduced ejection fraction, and fractional shortening [70]. Electromyography and muscle biopsy show myopathy [57,62]. The presence of ipecac can be confirmed in biopsy or necropsy tissue by high performance liquid chromatography [72].
Discussion While syrup of ipecac has been available as OTC since 1965 to induce emesis for certain poisonings (21 CFR 201.308), its unexpected abuse has been described in the last twenty-odd years. The epidemiological data available are quite compelling [33,50]. A limitation of this information is that its main source stems from a somewhat biased sample, as it originates in specialized eating disorders clinics, rather than from a general population study [49,50]. It could be argued that since only the sickest patients attend these clinics, their data on the use of ipecac is much higher than what one would see in a non-patient population with eating disorders. On the other hand, one could equally argue that this information is the proverbial tip of the iceberg, and that the abuse of ipecac may be even higher among those who refuse to see a doctor or are taken care of by professionals who have not had sufficient training or experience in the field of eating disorders to become suspicious of ipecac abuse [20]. While admitting that there are currently no direct population studies of ipecac abuse, combining the available data with clinical experience suggests that ipecac abuse among female adolescents and young women must be considered a serious health issue [20]. Since the source of ipecac syrup is of course the legal over-the-counter purchase of syrup of ipecac, it is reasonable to postulate that if the purchase would require a prescription it would make ipecac abuse much harder to practice. If ipecac were removed from sales, the toxicity would end. Arguments relating to the ineffectiveness of syrup of ipecac have been made repeatedly, and the product is no longer used in Europe [16]. The American Academy of Pediatrics no longer recommends its storage at home nor its use for prevention of pediatric poisonings [18]. The FDA is currently looking at this issue. In a recent hearing, an advisory panel voted 6 to 4 that ipecac syrup should no longer be available over the counter [21]. It is even possible that, if taken out of the “over-the-counter” category, ipecac syrup may not qualify for the prescription track, in which case it would no longer be available [65]. Thus, ipecac abuse could end in the same way as death from tincture of ipecac ended when that preparation was removed from the market in 1975. Since it is unlikely, because of the time and high cost necessary for a pharmaceutical company to file a New Drug Application for marketing ipecac as a prescription drug, a decision to remove its OTC status would actually lead to “the demise of ipecac” [76]. On the other hand, were ipecac syrup to survive as an over-the-counter medication, or unexpectedly be approved as a prescription medication, it will become increasingly necessary to further educate health professionals, including pharmacists, about its toxicity and potential for abuse. Moreover, more stringent warning labels would need to be added (Table 1).
T.J. Silber / Journal of Adolescent Health 37 (2005) 256 –260 Table 1 Proposed warnings re. lpecac syrup abuse ● Use of ipecac to repeatedly self induce vomiting is hazardous to your health ● Repeated use of ipecac is poisonous and can induce muscle weakness and pain secondary to muscle destruction ● Ipecac toxicity from repeated use can lead to cardiac damage, arrhythmia and death ● If you are abusing or have abused ipecac, seek professional advice.
Conclusions Ipecac abuse is a secret and compulsive activity engaged predominantly by female adolescents and young women for the purpose of weight loss/weight control [20,33,49,50,71]. This review of the medical literature confirms that it may result in severe morbidity and mortality [22–32,53– 62]. Recently, the effectiveness and efficacy of ipecac syrup for the prevention of childhood poisoning has been questioned [5–18,20 – 65]. In the absence of convincing evidence favoring the use of ipecac for this purpose, it makes sense to remove ipecac from its over-the- counter status, as this would significantly reduce its potential for abuse. However, if ipecac syrup were allowed to continue its OTC status, or given approval as a prescription drug, more stringent warning labels ought to be included, and further education be provided regarding its potential abuse. Based on the evidence presented, all those who care for adolescents and young adults struggling with eating disorders would certainly urge the FDA to accept the recommendations of the Nonprescription Drugs Advisory Committee to revoke the OTC status of ipecac syrup [20,21]. This would give a new lease on life to those who are “hooked on the bulimic drug” and prevent new generations from entering this dangerous path. It is time to remove ipecac from its over-the-counter status. Acknowledgments Based on an invited testimony to the Center for Drug Evaluation and Research Office of Executive Programs, U.S. Food and Drug Administration, Bethesda, Maryland, June 12th, 2003 and a presentation from the podium to the International Conference on Eating Disorders, American Academy for Eating Disorders, April 29, 2004, Orlando, Florida. References [1] [2] [3] [4]
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