Correspondence

Seizure Associated with the Use of Visicol for Colonoscopy

N Engl J Med 2002; 346:2095June 27, 2002

Article

To the Editor:

Visicol (InKine Pharmaceutical), which contains 1.5 g of sodium phosphate per tablet, is a bowel evacuant for colonoscopy that was approved by the Food and Drug Administration (FDA) in September 2000. Its proposed mechanism of action is an osmotic effect. Twenty tablets are taken the evening before the colonoscopy (three tablets with at least 8 oz of clear liquids every 15 minutes [the last dose being two tablets]) and again the next morning.1 From April to July 2001, four reports of tonic–clonic seizure associated with the administration of Visicol were received by the FDA MedWatch system (Table 1Table 1Summary of Case Reports.).2 The seizures occurred in adults who had no history of seizure or electrolyte abnormalities. The seizures occurred after the initiation of Visicol treatment, before colonoscopy, and have not recurred. All cases were associated with electrolyte abnormalities after the administration of Visicol and with seizure.

Sodium phosphate–containing enemas and liquid purgatives have been associated with reports of electrolyte abnormalities, cardiac arrhythmias, tetany, and death.1,3,4 These complications often occurred in patients with concomitant renal insufficiency or bowel perforation or after improper use.1,3,4 Although electrolyte abnormalities were reported in clinical trials of Visicol, no clinical sequelae were reported.1 Other adverse events reported to the FDA in association with the use of Visicol include esophageal perforation, mental-status changes, and vomiting. One death has been reported, although causation could not be established.5 There have been five reports of seizure associated with non-phosphate bowel preparations, three of which were confounded by preexisting medical conditions or a history of seizures.5 The FDA has not received any reports of seizure associated with other sodium phosphate–containing preparations on the market.

The temporal relation between the administration of Visicol and seizure in the absence of other recognized causes of seizure suggests a potential causal association. Disturbances in serum electrolyte levels and associated hypo-osmolality, recognized to occur with Visicol, are also known to increase the risk of seizures. Colonoscopy is a common procedure, and physicians should be aware of the possible risks associated with the administration of Visicol in preparation for the procedure.

Ann Corken Mackey, R.Ph., M.P.H.
Douglas Shaffer, M.D., M.H.S.
Robert Prizant, M.D.
Food and Drug Administration, Rockville, MD 20857
corkena@cder.fda.gov

5 References

1. 1

   Visicol product label. Blue Bell, Pa.: InKine Pharmaceutical, July 27, 2001. (Accessed June 6, 2002, at http://www.visicol.com/prescribinginformation.htm.)
   

2. 2

   Kessler D. Introducing MEDwatch: a new approach to reporting medication and device adverse effects and product problems. JAMA 1993;269:2765-2768
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   Vukasin P, Weston LA, Beart RW. Oral Fleet Phospho-Soda laxative-induced hyperphosphatemia and hypocalcemic tetany in an adult: report of a case. Dis Colon Rectum 1997;40:497-499
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4. 4

   Science background: safety of sodium phosphates oral solution. Rockville, Md.: Food and Drug Administration, September 17, 2001. (Accessed June 6, 2002, at http://www.fda.gov/cder/drug/safety/sodiumphospate.htm.)
   

5. 5

   Adverse Event Reporting System (AERS). Rockville, Md.: Center for Drug Evaluation and Research, Food and Drug Administration, July 2001. (Accessed June 6, 2002, at http://www.fda.gov/cder/aers/default.htm.)
   

Author/Editor Response

Spokespersons for InKine, the manufacturer of Visicol, reply:

To the Editor: Visicol has been prescribed more than 210,000 times since its introduction last year. Mackey et al. describe four patients with seizures after the use of Visicol for colonic cleansing and suggest that the risk of seizures may be greater with this product than with other purgatives. We take issue with this suggestion.

All four patients discussed by Mackey et al. had severe hyponatremia, which was the most likely cause of their seizures. Hyponatremia could have resulted from sodium losses through gastrointestinal mechanisms or sweating, excessive free-water ingestion, and excessive secretion of antidiuretic hormone. Potential contributing factors not identified by Mackey et al. include hypoparathyroidism, strenuous exercise during hot weather, the administration of two 20-tablet doses of Visicol two to three hours apart, and daily use of a laxative containing polyethylene glycol (PEG).

Neurologic dysfunction as a result of elevated antidiuretic hormone levels with hyponatremia has been reported after colonoscopy and the use of a PEG-containing product as a purgative.1 Also, among 40 patients who received a PEG-containing product as a purgative, 25 percent had elevated antidiuretic hormone levels just before undergoing colonoscopy and 7.5 percent had hyponatremia just after undergoing colonoscopy.2 The investigators attributed the elevated antidiuretic hormone levels to the nausea, vomiting, and abdominal hyperactivity associated with the use of PEG-containing purgatives; other possible causes include hypovolemia and hypotension.3

Neurologic symptoms of hyponatremia include confusion, somnolence, loss of consciousness, and seizures.3 The FDA's data base indicates that all these adverse events, as well as others, have been attributed to the use of PEG-containing products (Table 1Table 1Selected Adverse Events in the FDA Adverse Event Reporting System as of October 31, 2001, in Which a Product Containing Polyethylene Glycol Was Thought to Be a Primary Cause.). The data suggest that sodium phosphate tablets and PEG-containing purgatives can cause hyponatremia, which in rare cases may lead to seizures. The growing adoption of a regimen involving reduced doses of sodium phosphate tablets and reduced volumes that is described by Rex et al.4 may further decrease the likelihood of hyponatremia and may have contributed to the apparent absence of new cases of seizures since July 2001.

Martin Rose, M.D., J.D.
Leonard S. Jacob, M.D., Ph.D.
InKine Pharmaceutical, Blue Bell, PA 19422

4 References

1. 1

   Shroppel B, Segerer S, Keuneke C, Cohen C, Schlondorff D. Hyponatremic encephalopathy after preparation for colonoscopy. Gastrointest Endosc 2001;53:527-529
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2. 2

   Cohen CD, Keuneke C, Schiemann U, et al. Hyponatraemia as a complication of colonoscopy. Lancet 2001;357:282-283
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3. 3

   Baylis PH. Vasopressin and its neurophysin. In: DeGroot LJ, Besser GM, Cahill GF Jr, et al., eds. Endocrinology. 2nd ed. Vol. 1. Philadelphia: W.B. Saunders, 1989:213-29.
   

4. 4

   Rex DK, Chasen R, Pochapin MB. Safety and efficacy of two reduced dosing regimens of sodium phosphate tablets for preparation prior to colonoscopy. Aliment Pharmacol Ther 2002;16:937-944
   CrossRef | Web of Science | Medline

Citing Articles (14)

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1. 1

   Masahiro Tajika, Tsuneya Nakamura, Junya Tsuboi, Vikram Bhatia, Hiroki Kawai, Kenji Yamao. (2009) Syndrome of inappropriate secretion of antidiuretic hormone after endoscopic submucosal dissection for early gastric cancer. Clinical Journal of Gastroenterology 2:4, 262-265
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2. 2

   Kaitlin E. Occhipinti, Jack A. Di Palma. (2009) How to choose the best preparation for colonoscopy. Nature Reviews Gastroenterology & Hepatology 6:5, 279-286
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3. 3

   J. BELSEY, O. EPSTEIN, D. HERESBACH. (2009) Systematic review: adverse event reports for oral sodium phosphate and polyethylene glycol. Alimentary Pharmacology & Therapeutics 29:1, 15-28
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4. 4

   G. R. LICHTENSTEIN, L. B. COHEN, J. URIBARRI. (2007) Review article: bowel preparation for colonoscopy - the importance of adequate hydration. Alimentary Pharmacology & Therapeutics 26:5, 633-641
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5. 5

   Jerry Nagler, David Poppers, Meredith Turetz. (2006) Severe Hyponatremia and Seizure Following a Polyethylene Glycol-based Bowel Preparation for Colonoscopy. Journal of Clinical Gastroenterology 40:6, 558-559
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6. 6

   2006. Laxatives. , 2008-2013.
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   2006. Appendix: List of miscellaneous compounds. , 3737-3739.
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8. 8

   M. Rose. (2005) Renal failure following bowel cleansing with a sodium phosphate purgative. Nephrology Dialysis Transplantation 20:7, 1518-1519
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9. 9

   F. A. Frizelle, B. M. Colls. (2005) Hyponatremia and Seizures After Bowel Preparation: Report of Three Cases. Diseases of the Colon & Rectum 48:2, 393-396
   CrossRef

10. 10

    Andrew R. Brown, Jack A. DiPalma. (2004) Bowel preparation for gastrointestinal procedures. Current Gastroenterology Reports 6:5, 395-401
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11. 11

    Larry E Clark, Jack A DiPalma. (2004) Safety Issues Regarding Colonic Cleansing for Diagnostic and Surgical Procedures. Drug Safety 27:15, 1235-1242
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12. 12

    (2002) Current Awareness: Pharmacoepidemiology and Drug Safety. Pharmacoepidemiology and Drug Safety 11:8, 727-742
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13. 13

    Rose, Martin, Jacob, Leonard S., . (2002) Seizure Associated with Use of Visicol for Colonoscopy. New England Journal of Medicine 347:4, 295-296
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14. 14

    &NA;. (2002) Sodium phosphate. Reactions Weekly &NA;:910, 10
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