Clinical Gastroenterology and Hepatology
Volume 7, Issue 10 , Pages 1138-1139, October 2009

Reply

published online 24 August 2009.

Article Outline

 

Dr Bernstein identifies an important warning from the FDA issued on February 26, 2009. I could not have incorporated the warning in a paper published in 2007. Moreover, the current perspective (submitted to the journal September 11, 2008, accepted November 4, 2008, and published online soon after that date) was written to highlight therapeutic opportunities in enhancing glycemic control in patients with diabetes.

The FDA release stated, “Chronic use of metoclopramide has been linked to tardive dyskinesia, which may include involuntary and repetitive movements of the body,” but it falls shy of any determination of the true prevalence of metoclopramide-induced tardive dyskinesia. In Ganzini et al,1 which is cited by Parkman et al,2 it is stated that the relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93–2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5–10.5).1 It is therefore unclear how Parkman et al2 or Dr Bernstein determined that the “incidence of tardive dyskinesia is 1% to 10%.”

The FDA also recommends that “metoclopramide therapy should be avoided in all but rare cases where the benefit is believed to outweigh the risk.” As stated in the perspective, there is currently no other FDA-approved pharmacological treatment for gastroparesis. Moreover, there is increasing evidence that diabetic gastroparesis is associated with increased hospitalizations, doctor visits, and mortality.3, 4

Experienced clinicians have used this medication judiciously and safely by never exceeding a total of 40 mg (or 0.5 mg/kg) per day, starting with a test dose of 5 mg orally to check for idiosyncratic responses in metoclopramide-naïve patients, and using 5 mg liquid formulations orally in patients with gastroparesis to ensure that the medication empties from their stomachs. This is preferable to running the risk of accumulating metoclopramide tablets in the stomach and subsequent delivery of higher doses when the stomach actually empties.

Any unneeded medication should be stopped. It is reasonable to try stopping metoclopramide after 3 months; however, clinical experience over 30 years has taught me that this is associated with recurrence of symptoms, malnutrition, and hospitalization with attendant complications in patients with gastroparesis. There is increased mortality in patients with objective evidence of impaired gastric emptying.4 In many patients with moderate or severe gastroparesis (as classified in Camilleri5), the benefits of metoclopramide to individual patients observed in practice outweigh the risks. The risk of tardive dyskinesia in patients with gastroparesis increased with the withdrawal of cisapride6 and the lack of safe and effective medications as alternatives to metoclopramide. To cite an oft-quoted cliché, the status quo is unacceptable, and patients with gastroparesis deserve a concerted effort on the part of drug developers, clinicians, learned societies, and regulators to bring safe and effective treatments to clinical practice.

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References 

  1. Ganzini L, Casey DE, Hoffman WF, et al. The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med. 1993;153:1469–1475
  2. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1592–1622
  3. Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995–2004. Am J Gastroenterol. 2008;103:313–322
  4. Hyett B, Martinez FJ, Gill BM, et al. Delayed radionucleotide gastric emptying studies predict morbidity in diabetics with symptoms of gastroparesis. Gastroenterology. 2009;137:445–452
  5. Camilleri M. Clinical practice (Diabetic gastroparesis). N Engl J Med. 2007;356:820–829
  6. Shaffer D, Butterfield M, Pamer C, et al. Tardive dyskinesia risks and metoclopramide use before and after US market withdrawal of cisapride. J Am Pharm Assoc. 2004;44:661–665

 Conflicts of interest The author discloses no conflicts.

PII: S1542-3565(09)00778-2

doi:10.1016/j.cgh.2009.08.016

Refers to article:

  • Warnings on Metoclopramide Treatment , 08 May 2009

    Ralph Bernstein
    Clinical Gastroenterology and Hepatology October 2009 (Vol. 7, Issue 10, Page 1138)

Clinical Gastroenterology and Hepatology
Volume 7, Issue 10 , Pages 1138-1139, October 2009