# Presentation: 171805

## Presentation for the
Center for Drug Evaluation and Research
Office of executive Programs, US Food and Drug Administration
June 12, 2003

**Center for Drug Evaluation and Research**
**Office of executive Programs, US Food and Drug Administration**
**June 12, 2003**

**Ipecac Abuse****Tomas J Silber, MD, MASS**** *****Children’s National Medical Center***** Division of Adolescent Medicine ****Department of Pediatrics, GWU**

## 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**

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

## Ipecac Abuse=Adolescent and Young Adult Population

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

- Secret
- Addictive
- Denial
- Lying

## 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.**

## 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**

## 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**

## Recurrent Vomiting: Dental Abnormalities

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

## Recurrent Vomiting: Gastrointestinal Abnormalities

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

## 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**

## Diarrhea

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

## Myopathy

**Progressive weakness in proximal muscles**
**Myalgia**
**Loss of deep tendon reflexes**
**Swallowing difficulty**
**Slurred speech**

## 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**

## Cardiac Abnormalities

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

## EKG Changes

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

## Echocardiography:
Ventricular dysfunction 
Reduced ejection fraction

Electron microscopy of myocardium:
Zones of myofibrillar lysis
Fragmented fibers
Irregular alignments or clumps of Z bands

**Ventricular dysfunction **
**Reduced ejection fraction**
_**Electron microscopy of myocardium:**_
**Zones of myofibrillar lysis**
**Fragmented fibers**
**Irregular alignments or clumps of Z bands**

## Miscellaneous

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

## 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**

## Detection

**High index of suspicion**** **
_**Laboratory**_
**	****EKG**
**	****CPK-aldolase**
_**Confirmation**_** **
**(high performance liquid chromatography)**
**	****In serum**
**	****In urine**
**	****In tissue**

## 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**

## 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.**