Visicol® Tablets (InKine Pharmaceutical Co., Inc.) have been used in >1.2 million patients as a bowel preparation for colonoscopy. To date, InKine Pharmaceuticals has received one report of nephrocalcinosis following use of Visicol®. This case was described by Markowitz et al. in the April 2005 issue of the journal along with 15 cases associated with the use of oral sodium phosphate solution (OSPS, Fleet® Phospho®-Soda, C.B. Fleet). Data reported to InKine indicate that this patient had at least three important risk factors for the development of acute renal failure (ARF) and nephrocalcinosis.
First, the patient had a history of renal insufficiency with a rising creatinine (1.7 mg/dl) and had been on meloxicam (Mobic®, Boehringer Ingelheim) for years. This was discontinued just prior to colonoscopy, but was restarted within 1 month for shoulder pain. Visicol® should be used with caution in patients with impaired renal function since they may have difficulty excreting large phosphate loads. It should be noted that the post-colonoscopy creatinine level was much smaller in this patient (2.6 mg/dl 2 months post-colonoscopy) than in the patients receiving OSPS (mean of 4.9 mg/dl 3 days to 2 months post-colonoscopy). It is unknown how much the meloxicam may have contributed to the rising creatinine. In January 2005, the patient's creatinine was 2.2 mg/dl.
Secondly, since 2002, the patient was taking 10 mg of ramipril (Altace®, Monarch Pharmaceutical), an angiotensin-converting enzyme inhibitor (ACEI), which is twice the recommended daily dose for patients with renal insufficiency. Because ACEIs limit the kidneys' normal capacity to compensate for the stress of volume depletion, patients on these drugs can experience a decrease in glomerular filtration rate and possible renal failure when in a volume-depleted state, e.g. following the use of a purgative.
Thirdly, this 44-year-old patient presented with a 1 week history of abdominal pain, bloody stools and no relevant family history. The patient underwent colonoscopy within 2 days of presentation. A diagnosis of acute and chronic colitis was made. Patients with acute colitis are at risk for excess phosphate absorption [1].
Since patients who take a purgative experience diarrhoea and in some cases vomiting, every patient is at risk for developing dehydration and hypovolaemia, which can result in renal failure. Physicians should assess patients' hydration status prior to beginning any bowel purgative. In this case, there was no information provided on the hydration status of the patient although the patient was prescribed a 3 day bowel preparation regimen consisting of bisacodyl tablets and clear liquids the day prior to starting Visicol® Tablets. The recommended Visicol® bowel preparation is taken over 2 days without other laxatives. A 3-day bowel preparation may predispose a patient to dehydration.
Vomiting contributes to dehydration and has been shown to contribute to the non-osmotic release of anti-diuretic hormone [2], which after a purgative has produced non-fatal hyponatraemic encephalopathy with sodium phosphate [3] and fatal hyponatraemic encephalopathy with PEG solution [4]. Two phase III trials comparing Visicol® with 4L PEG solution (Cherry NuLYTELY, Braintree Laboratories) for bowel cleansing in 845 patients showed a 50% reduction in the incidence of vomiting in patients taking Visicol® (P = 0.0001) [5]. In one trial comparing OSPS with 4L PEG, OSPS was associated with a higher incidence of vomiting and an increase in reported thirst and dryness (P = 0.00001) [6]. If a patient experiences vomiting or is unable to take fluids prior to or after colonoscopy, the patient should be told to contact their physician.
Nephrocalcinosis is a very rare event following the administration of sodium phosphate for bowel preparation. In a recent publication, Markowitz and Perazella state: Prevention of this form of ARF requires maintenance of adequate volume repletion prior to and during phosphate administration [7]. Physicians should continue to instruct patients to ingest 8 oz of fluid with each dose of Visicol® tablets every 15 min to maintain adequate hydration. In addition, careful management of gastrointestinal fluid losses, including vomiting, should be emphasized with all purgatives.
Conflict of interest statement. M.R. and R.G.K are employees of InKine Pharmaceutical and have an equity interest in the company. K.W. is a contract employee of InKine Pharmaceutical.
InKine Pharmaceutical Co. Inc. Blue Bell PA 19422 USA Email: kwalker{at}inkine.com
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