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Acute pancreatitis and modified-release clarithromycin

Gastroenterologist Digestive Unit Hospital General Mancha-Centro Avda. Constitución s/n 13600 Alcázar de San Juan Ciudad Real, Spain fax 34-926547700 psgc{at}mixmail.com

Francisco Pérez Roldán, MD

Gastroenterologist Digestive Unit Hospital General Mancha-Centro

Maria Luisa Legaz Huidobro, MD

Gastroenterologist Digestive Unit Hospital General Mancha-Centro

Manuel Moraleda de Acuña, MD

Fellow Gastroenterologist Digestive Unit Hospital General Mancha-Centro

Juan Carlos Nieto García, MD

Radiologist Hospital General Mancha-Centro

Published Online, January 30, 2004. www.theannals.com, DOI 10.1345/aph.1D288

Case Report. A 43-year-old man presented with abdominal pain. His medical history included a perforated tympanum with episodes of acute otitis media. There was no history of alcohol or narcotic ingestion, and there was no other illness. There also was no history of pancreatic disease. The pain had begun 20 minutes after the patient took clarithromycin 500 mg in the form of modified-release tablets after the onset of otic infection; however, he did not come to the hospital until 48 hours after onset. Laboratory test results showed total leukocyte value 14.8 x 10³/mm³, amylase level 198 IU/mL (range 0-100), lactate dehydrogenase 727 IU/mL (260-450), and C-reactive protein 18.5. Tests of hepatic function were normal. The ultrasound did not reveal gallstones, and the axial abdominal tomographic scan showed inflammatory changes in the peripancreatic fat and pancreatic fluid in the left pararenal anterior space which spread toward the left gutter with partial necrosis (<30%). The magnetic resonance cholangiography was normal. The patient was discharged after 10 days. Given the clear causal link between the appearance of pancreatitis and the ingestion of the drug and the normal values obtained in hepatic function tests, it was considered unnecessary to carry out an endoscopic retrograde cholangiopancreatography.

Discussion. Erythromycin is considered to be a motiline agonist of the smooth gastrointestinal musculature with a proven prokinetic action. The drug also acts as a stimulant in the sphincter of Oddi, provoking possible secondary biliary reflux toward the pancreatic duct, thus triggering the inflammatory cascade of acute pancreatitis.² However, this mechanism was not corroborated after the discovery by Wehrmann et al.³ of the existence of a decrease in both the base pressure of the sphincter of Oddi and the frequency of phasic contractions in humans with the use of erythromycin. However, investigators also demonstrated that the administration of erythromycin produces an increase in the average duration of the phasic contractions of the sphincter, as well as in their amplitude.

Clarithromycin, as a macrolide, also has a prokinetic effect similar to that of erythromycin, although of a shorter duration, on the gallbladder and in the gastric antrum. There is no reliable hypothesis regarding clarithromycin's mechanism of action on the biliopancreatic sphincter.⁴ Clarithromycin is widely used in our environment and is responsible for a considerable incidence of gastrointestinal secondary effects, among which the appearance of acute pancreatitis is exceptional. Use of the Naranjo probability scale indicates a probable relationship between acute pancreatitis and modified-release clarithromycin.⁵

References

1. Liviu L, Yair L, Yehuda S. Pancreatitis induced by clarithromycin.Ann Intern Med 1996;125:701-3.[Free Full Text]
2. Peeters TL. Erythromycin and other macrolides as prokinetic agents.Gastroenterology 1993;105:1886-99.[Medline]
3. Wehrmann T, Pfeltzer C, Caspary WF. Effect of erythromycin on human biliary motility. Aliment Pharmacol Ther 1996;10:421-6.[Medline]
4. Acalovschi M, Dumitrascu DL, Hagiu C. Oral clarithromycin enhances gallbladder emptying induced by a mixed mela in healthy subjects. Eur J Intern Med 2002;13:104-7.[Medline]
5. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions.Clin Pharmacol Ther 1981;30:239-45.[Medline]

This Article PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carro, P. G. Articles by García, J. C. N. Search for Related Content PubMed PubMed Citation Articles by Carro, P. G. Articles by García, J. C. N.