Quzilbash_edit_final_Layout 1 06/10/2009 11:44 Page 20
Endoscopy
Table 4: Summary of Medically Confirmed Serious temporary changes and not permanent kidney damage. For
Cases by Year and Country
example, Singal et al.
9
identified three cases (two exposed to PEG
and one to OSP) in their study with post-colonoscopy increases of
Country 2007 2008 1st QTR 2009
>2mg/dl; all three patients had a return of their creatinine to pre-
Belgium 0 2 0
colonoscopy levels within six months.
Denmark 1 0 0
Finland 1
Case Reports and Case Series
France 4 5 1
Germany 1 4 0
Case reports and series are the least valid clinical designs to assess
Greece 1 0
questions of causality, except when the risks are high and the
Iceland 0 9
events are rare so that moderate biases can be ignored. However,
Netherlands 1 2 0 they do play a valuable role in generating hypotheses to be tested
Norway 2 3 with more valid study designs.
Poland 0 1 0
Spain 3 2 1
Many published reports of cases associated with renal insufficiency
Sweden 0
have occurred after doses above the recommended dose (15%) and
UK 2 2 0
in patients with pre-existing chronic renal failure (20%), which is a
Total 16 23 12
contraindication for OSP. Only 8.8% of cases emanated from Europe.
Table 5: Rates for Reported, Medically Confirmed
Cases for Phospho-soda
Other factors identified were hypertension, diabetes or both, in
65%. However, these factors did not emerge from the
Medically Unit Sales Rate per
epidemiological studies. On the other hand, some of the
Confirmed (Two Doses) Million medications associated with these conditions can cause electrolyte
Cases Unit Sales
disorders and reduction in vascular volume that may have occurred
2007
causing renal impairment when OSP was administered.
EU medically confirmed total 16 2,067,555 7.74
EU medically confirmed renal 6 2,067,055 2.90
The figures of 1.2% and 0.3% from two case series are not
2008
supported by epidemiological studies or randomised trials.
EU medically confirmed total 23 2,157,327 10.66
EU medically confirmed renal 13 2,157,327 6.03
Furthermore, the reporting rate of serious renal events in the Fleet
company database for Phospho-soda in 2007 and 2008 was
First Quarter 2009 (SAE numbers only)
EU medically confirmed total 12
between 2.9 (six cases) and 6.03 (13 cases) per million units sold in
EU medically confirmed renal 12
Europe, respectively.
Serious adverse event rates for reported medically confirmed cases for Phospho-soda
products (excluding Prep Kits 1, 2 and 3) reported as of 8 April 2009. Conclusions
OSP products have been established worldwide for many years as
controls (adjusted odds ratio [OR] 0.70, 95% confidence interval [CI] first-line agents in terms of superior efficacy compared with
0.44–1.11). Sensitivity analyses that considered other definitions of PEGs.
4,5,7
OSP products are also better tolerated with greater
kidney injury did not lead to different conclusions. When patients compliance.
4,5,7,24
Adverse events are considered comparable
with a serum creatinine increase of >1mg/dl were analysed as a between OSPs and PEGs. Renal events have not been reported in
subgroup, they arrived at an incidence of seven per 10,000 for OSP. randomised, prospective trials.
4,5,7
A statistical interaction with exposure to concomitant OSP and
ACE-I/ARB use was also found in this study. Controlled epidemiological studies, all conducted in North America,
indicate that when pre-existing renal impairment is present the
The study of Russman et al.
60
showed that in patients without pre- increased risk of acute kidney injury with use of OSP is high and
existing renal disease (GFR >60ml/minute), the risk of renal incontrovertible; pre-existing renal impairment is a well-established
impairment after colonoscopy appears to be similar between OSP contraindication for the use of OSP. Other epidemiological studies
and PEG users. However, patients with a GFR <60ml/minute showed provided mixed results. No clear risk factors for renal injury were
that OSP use was associated with a significant increased risk of identified except pre-existing renal impairment. The clinical
renal dysfunction compared with use of PEG.
56
consequences of the small increases in creatinine used to define
acute renal injury in these studies may be temporary and may not be
The study by Singal et al.
9
found a small statistically significant associated with long-term or permanent renal impairment.
increase in mean creatinine for OSP compared with PEG. OSP was
associated with a statistically significant ≥25% increase in Renal events from published case reports arose almost entirely from
creatinine but not with a ≥50% increase in creatinine. This may North America, suggesting a difference in clinical practice, which may
indicate that the slight increase in creatinine is not clinically result from the differing regulatory status of the products in North
significant, although the study may have been underpowered due America (where they were OTC products) and Europe (where they are
to its small size. mostly prescription products).
It is important to note that some of the cases defined in these The reporting rate of serious renal impairment in the Fleet company
epidemiological studies as representing acute kidney injury (e.g. a database in 2007 and 2008 was between 2.9 and 6.03 per million units
rise in creatinine of 50% post-baseline) may represent only of Phospho-soda sold in Europe.
20 EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76