Washington, D.C.

Presentation for the

Center for Drug Evaluation and Research

Office of executive Programs, US Food and Drug Administration

June 12, 2003

Ipecac AbuseTomas J Silber, MD, MASS

Children’s National Medical Center Division of Adolescent Medicine Department of Pediatrics, GWU

Washington, D.C.

Review of Ipecac Syrup for OTC Status (21 CFR 201.308)

• Role in gastrointestinal decontamination• Risk benefit ratio• Role in the treatment for populations with

limited access to emergency medical treatment

• Abuse of ipecac syrup• Alternative therapies

Abuse of ipecac syrup

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Ipecac Abuse: DefinitionIpecac abuse consists of the repeated use of the syrup for the sole purpose of self-inducing emesis as a method of weight control

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Ipecac Abuse=Adolescent and Young Adult Population

• Experimenters• Eating Disorder, NOS• Anorexia Nervosa, purging type• Bulimia Nervosa

Secret

Addictive

Denial

Lying

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Epidemiology of Self-Induced Vomiting*

• Anorexia Nervosa: Prevalence, lifetime 0.1 to 1%

• Between 8 to 41% of individuals with Anorexia Nervosa with develop Bulimia Nervosa

(Bulik CM: Eating Disorders in adolescents and young adults. Child and Adol Psychiatri Clin N Am 2002(11):201-218.)

• Bulimia Nervosa: Prevalence, lifetime 3%

(Fairburn CG, Beglin SJ: Studies of the epidemiology of bulimia nervosa. Am J Psychiatry 1990;147:401-408.)

*There is no data on the incidence and prevalence of the use of ipecac to self-induce vomiting.

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Adverse Events (AE)

• OTC do not require submission of AE to the FDA

• Therefore, AE data are very limited

• However, all reports are consistent with Ipecac’s characteristic effects

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Signs and Symptoms of Ipecac Poisoning*

• Recurrent vomiting• Diarrhea• Abdominal cramping• Muscle pain and

stiffness• Muscle weakness• Myopathy

• Erythema• Urticaria• Edema• Cardiomyopathy• Cardiac insufficiency• Cardiac arrhythmias

Death - n=6 (4 due to ipecac abuse)

*Lee L, Karwoski C: Post-Marketing Safety Review - PID# D030159 - May, 6, 2003

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Recurrent Vomiting: Dental Abnormalities

• Tooth enamel dissolves• Sensitive teeth• Increased caries• Pyorrhea, periodontal disease• Loss of teeth• Parotid gland enlargement

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Recurrent Vomiting: Gastrointestinal Abnormalities

• Esophagitis• Reflux• Barrets esophagus• Dysphagia - odynophagia• Esophageal strictures• Mallory Weiss Tears• Hematemesis• Aspiration pneumonitis

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Recurrent Vomiting: Metabolic Abnormalities

• Metabolic alkalosis• Hypokalemia: fatigue, muscle weakness,

polydipsia, nocturia, abdominal pain, constipation, headaches, palpitations, renal pathology (Barters Syndrome)

• Dehydration - shock• Sudden death

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Diarrhea

• Dehydration• Secretory diarrhea• Hemorrhagic colitis• Pseudo melanosis• Intestinal pseudo-obstruction

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Myopathy

• Progressive weakness in proximal muscles

• Myalgia• Loss of deep tendon reflexes• Swallowing difficulty• Slurred speech

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Myopathy*

• Persistent increase in phosphokinase and aldolase

• Electromyographic features of toxic myopathy

• Muscle biopsy: severe disruption of sarcomeres sarcotubular lesions

• Electron microscopy: foci of Z-band degeneration

*Reversible with cessation of use

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Cardiac Abnormalities

• Cardiomyopathy• Cardiomegaly• Tricuspid and mitral valve insufficiency• Decreased cardiac ejection fraction• Hypotension• Arrhythmias• Death

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EKG Changes

• Sinus tachycardia• T wave depression and inversion• Prolonged PR interval and QTc• Atrial tachycardia• Atrial premature beats• Ventricular tachycardia• Ventricular fibrilation

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Echocardiography:

Ventricular dysfunction

Reduced ejection fraction

Electron microscopy of myocardium:

Zones of myofibrillar lysis

Fragmented fibers

Irregular alignments or clumps of Z bands

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Miscellaneous

• Pneumomediastinum• Pneumoperitoneum• Intestinal perforation• Hepatic toxicity• Cerebral hemorrhage• Seizures

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Munchausen Syndrome by Proxy

• Child abuse by poisoning

• Increasingly reported but probably underrecognized

• Severe recurrent pathology

• May end by causing the death of the child

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Detection

• High index of suspicion

Laboratory

EKG

CPK-aldolase

Confirmation

(high performance liquid chromatography)

In serum

In urine

In tissue

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Recommendations

• Studies are needed to determine incidence and prevalence of ipecac abuse

• Promote professional education re: ipecac abuse to facilitate early detection and treatment

• Develop preventive methods. Depending on risk-benefit ration, this may include status change from OTC to prescription medication, and/or

• Warnings about the danger of abuse should be included

• Labeling should indicate the maximum total dose or maximum number of times the dose should be repeated

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Example of Warnings

•Use of ipecac to repeatedly self-induce vomiting is hazardous to your health.

•Prolonged use of ipecac is poisonous and can induce among others muscle weakness and pain secondary to muscle destruction.

•Ipecac toxicity can lead to cardiac damage, electrolyte imbalance and death.

•If you are or have abused ipecac, seek professional advice.