Open Journal of Gastroenterology, 2013, 3, 272-275 OJGas
http://dx.doi.org/10.4236/ojgas.2013.35046 Published Online September 2013 (http://www.scirp.org/journal/ojgas/)
Diphenyl methane laxatives do not induce electrolyte
Department of Internal Medicine, Park-Klinik Weissensee, Schönstrasse, Berlin
Received 2 July 2013; revised 5 August 2013; accepted 18 August 2013
Copyright © 2013 Stefan Müller-Lissner. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aim: To analyse whether there are changes in sodium
and potassium serum levels during chronic treatment
with the diphenyl methanes bisacodyl and sodium
picosulfate. Methods: A literature search was done
using PubMed, and the reference lists of pertinent
papers were screened for additional studies. Only
studies of at least 4 weeks duration were considered
for further analysis. Results: Four relevant studies
were identified. In three randomised controlled trials
with 5 to 10 mg daily of bisacodyl or sodium picosul-
fate, respectively, over four weeks no electrolyte losses
were found. Hypokalemia was also not a problem in a
group of patients with paraplegia using bisacodyl
suppositories for 2 to 34 years. Conclusions: Electro-
lyte losses, particularly hypokalemia, are not a prob-
lem when bisacodyl or sodium picosulfate are used
Keywords: Laxative; Bisacodyl; Sodium Picosulfate;
Hyponatremia; H ypokalemia
Consumer reports, whether printed or in the internet,
often contain warnings of side effects of laxatives, par-
ticularly of the so-called stimulan t laxatives. These com-
prise the anthraquinones (e.g. sennosides) and the di-
phenyl methane derivatives (bisacodyl and sodium pico-
sulfate) and exert a dual, namely a secretory and a pro-
kinetic action [1,2]. These warnings read e.g. “confusion,
irregular heartbeat, muscle cramps, and unusual tiredness
or weakness” [3-6 ].
Similar concerns have, to my knowledge, not been ex-
pressed regarding water binding laxatives (salinic laxa-
tives, sugars such as lactulose, and macrogol). Nor have
they been expressed for pure prokinetics such as pruca-
lopride and the new secretory stimulants lubiprostone
and linaclotide, potentially because the manufacturers
were hitherto successful in avoiding the term “laxative”
for these products.
If these side effects would occur they would occur with
almost certainty be due to electrolyte losses, particularly
of potassium. It is well known that induction of diarrhea
by these laxatives may lead to hypokalemia [7-9], but
this does not allow the conclusion that such losses may
also occur when the laxatives are used in the proper dose.
The purpose of the present paper is to present the
available data of sodium and potassium serum levels dur-
ing chronic treatment of chronic constipation with di-
A literature search was done using PubMed with the
terms (diphenyl methanes OR bisacodyl OR sodium pi-
cosulfate) AND (electrolytes OR sodium OR potassium)
and the available respective MeSH terms (“picosulfate
sodium” [Supplementary Concept]) AND (“Hypokale-
mia” [Mesh] OR “Water-Electrolyte Imbalance” [Mesh]).
In addition the reference lists of the papers were screened
for additional studies. Only studies of at least 4 weeks
duration were considered for further analysis. The manu-
facturer of bisacodyl and sodium picosulfate was then
asked to provide the original data on electrolytes from
the respective trials.
The oldest paper on the subject reports long-term data
from 101 patients with spinal cord injury using bisacodyl
over a period of 2 to 34 years. Patients used bisacodyl
suppositories, predominantly one to two suppositories
two or three times weekly . Only two patients had
potassium levels slightly below the lower limit of nor-
mality and without clinical relevance (Figure 1). How-
ever, no information is available regarding intake of
other drugs affecting serum electrolytes such as diuretics.
There are three randomised controlled trials with
S. Müller-Lissner / Open Journal of Gastroenterology 3 (2013) 272-275 273
Figure 1. Serum potassium levels in 88 paraplegic patients
chronically using bisacodyl suppositories. More than 80% of
the patients used bisacodyl for more than 5 years. Shaded area:
normal range. Data from 10.
orally administered diphenyl methanes over 4 weeks
each in patients with chronic constipation according to
the Rome II and Rome III criteria, respectively [11,12].
After a one to two weeks baseline period, patients were
randomized to one of two arms.
In the first open-label study, bisacodyl 5 to 10 mg was
compared to 5 to 10 mg sodium picosulfate daily in 144
patients . There was no difference regarding efficacy
between both drugs, and there were no losses of electro-
lytes as shown in Figure 2(A).
The second study compared bisacodyl 5 to 10 mg to
placebo in 368 patients , and the third study com-
pared sodium picosulfate 5 to 10 mg to placebo in 367
patients . As expected, active treatments were largely
superior to placebo. Figures 2(B) and (C) show the time
course of serum sodium and potassium in these double-
blind trials. Again, hypokalemia or hyponatremia did not
The designs of these trials are summarized in Table 1,
baseline characteristics of their patients are given in Ta-
Figure 2. Serum levels of sodium and potassium at the beginning and end of tre atme nt with bisacodyl, sodium picosulfate (SPS), and
placebo, respectively, for 4 weeks (means ± SD). Shaded area: normal range. (A) from Ref. ; (B) from Ref. ; (C) from Ref.
Table 1. Characteristics of published studies with bisacodyl or sodium picosulfate in chronically constipated patients giving details
on serum electrolyte s. SPS: sodium pic osulfa te .
patients Treatment arm 1 Treatment arm 2 Duration Reference
88 1 to 2 bisacodyl suppositories
2 to 3 times weekly None 2 to 34 years 
144 Bisacodyl 5 to 10 mg daily 5 to 10 mg SPS daily 4 weeks 
368 Bisacodyl 5 to 10 mg daily Placebo 4 weeks 
367 SPS 5 to 10 mg daily placebo 4 weeks 
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S. Müller-Lissner / Open Journal of Gastroenterology 3 (2013) 272-275
Table 2. Baseline data from studies with bisacodyl or sodium picosulfate in chronically constipated patients giving details on serum
electrolytes. SPS: sodium picosulfate.
Reference   
Number of patients on bisacodyl 70 247 -
Number of patients on SPS 74 - 233
Number of patients on placebo - 121 134
Number of females (n, %) 104 (67.5) 275 (74.7) 285 (77.7)
Age (years, s.d.) 62.7 (18.3) 55.4 (15.6) 50.8 (16.9)
Duration of constipation (years, s.d.) >6 months 21.2 (19.2) 13.2 (14.0)
Baseline stool frequency (per week, s.d.) 3.2 (1.2) 4.2 (1.1) 3.1 (1.1)
There were no differences regarding sex distribution, age, duration of constipation, and baseline stool frequency between the treatment groups within the three
The role of the colon is threefold, namely absorbing wa-
ter from intestinal contents, retaining, mixing and pro-
pelling feces, and allowing bacterial degradation of un-
digested nutrients such as dietary fiber. The latter con-
siderably contributes to the energy balance of species
with a large cecum such as rodents but is of minor im-
portance in man. About 2 liters of small intestinal juice
enter the colon each day being reduced to around 200 ml
of more or less solid feces. However, in diarrheal states
large amounts of fluids may be excreted. This fluid con-
tains electrolytes in concentrations isoosmotic to serum.
This holds true for both osmotic and secretory diarrhea.
Both anthraquinones and diphenyl methanes may induce
diarrhea when given in too high doses. This is a well
known effect in psychiatric patients abusing laxatives
such as anorexia nervosa or Munchhausen’s syndrome
[7-9,16]. Under these circumstances hypokalemia is the
most prominent and dangerous laboratory abnormality
potentially causing muscle weakness and kidney injury.
However, these psychiatric conditions definitely differ
from chronic laxative intake for constipation, e.g. since
the laxative intake is concealed by the users.
Diarrhea is the desired effect if laxatives are used in
bowel cleansing protocols. However, such protocols to-
day usually contain macrogol alone or in combination
with another laxative such as bisacodyl. Macrogol pre-
parations for bowel cleansing contain however electro-
lytes in isoosmotic concentration in order to prevent
electrolyte from shifting from blood to the colonic lumen.
Therefore, data from studies on bowel preparation are
not likely to show potential electro lyte losses induced by
bisacodyl and are not suited to refute such a side effect.
Rather the analysis had to focus on trials with one secre-
tory laxative only.
Since chronic constipation usually requires long-term
laxative intake, only studies of several weeks duration
were considered for further analysis. In addition, it is al-
ready known that short time treatment with bisacodyl or
sodium picosulfate does not affect serum electrolytes
Regarding longer treatment, the available data clearly
show that bisacodyl and sodium picosulfate as used both
in controlled trials and in open observations do not have
untoward effects on the electrolyte balance. This holds
true for trials over four weeks and for observations over
years and decades. On one hand, this is not surprising
since laxatives should be used by constipated patients in
doses not leading to diarrhea but to a soft formed stool.
However, as reported in nearly all trials with laxatives
diarrhea sometimes does occur although not intended.
This is reflected in the recent trials with bisacodyl and
sodium picosulfate, respectively, where patients were
allowed to lower the daily dose [14,15]. The fact that
about half of the patients on verum did so suggests some
diarrhea occurring with the full dose. However, these
days were obviously irrelevant with regard to serum
Can the compliance with the dose be extrapolated
from controlled trials to the real life situation? From an
observational study in constipated patients taking sodium
picosulfate, it is known that nearly all users adhere to the
recommendation regarding interval of intake and dose
. This makes it highly unlikely that the use of di-
phenyl methanes in daily practice will expose the users at
risk for electrolyte losses.
In summary, there is not only no indication that chro-
nic use of diphenyl methanes in recommended doses
may lead to electrolyte imbalance, particularly hypo kale-
mia, but controlled trials have specifically refuted this
 Binder, H.J. and Donowitz, M. (1975) A new look at
laxative action. Gastroenterology, 69, 1001-1005.
 Hervé, S., Savoye, G., Behbahani, A., Leroi, A.M., Denis,
P. and Ducrotté, P. (2004) Results of 24-h manometric
Copyright © 2013 SciRes. OPEN ACCESS
S. Müller-Lissner / Open Journal of Gastroenterology 3 (2013) 272-275 275
recording of colonic motor activity with endoluminal in-
stillation of bisacodyl in patients with severe chronic slow
transit constipation. Neurogastroenterology and Motility,
16, 397-402. doi:10 .1111/j.1365-2982.2004.00535.x
 Bundesvereinigung Deutscher Apothekerverbände, 2011.
 ADRAC (2002) Electrolyte disturbances with sodium
picosulfate bowel cleansing products. Australian Adverse
Drug Reactions Bulletin, 21, 1-4.
 (1997) Consumer reports complete drug reference, 981-
 Fruit-Eze, Inc. Laxative Warnings, Side Effects & Con-
traindications Reported in Medical Literature.
 Bytzer, P., Stokholm, M., Andersen, I., Klitgaard, N.A.
and Schaffalitzky de Muckadell, O.B. (1989) Prevalence
of surreptitious laxative abuse in patients with diarrhoea
of uncertain origin: A cost benefit analysis of a screening
procedure. Gut, 30, 1379-1384.
 Cummings, J.H., Sl ade n, G.E. , James, O.F. W. , Sarner, M.
and Misiewicz, J.J. (1974) Laxative-induced diarrhoea: A
continuing clinical problem. British Medical Journal, 1,
 Read, N.W., Krejs, G.J. and Read, M.G. (1980) Chronic
diarrhea of unknown origin. Gastroenterology, 78, 264-
 Ruidisch, M.H., Hutt, H.-J. and König, E. (1994) Laxan-
zien-langzeittherapie mit bisacodyl. Wirksamkeit und ver-
träglichkeit bei patienten mit rückenmarkverletzungen.
Ärztliche Forschung, 41, 3-8.
 Longstreth, G.F., Thompson, W.G., Chey, W.D., Hough-
ton, L.A., Mearin, F. and Spiller, R.C. (2006) Functional
bowel disorders. Gastroenterology, 130, 1480-1491.
 Thompson, W.G., Longstreth, G.F., Drossman, D.A.,
Heaton, K.W., Irvine, E.J. and Müller-Lissner, S.A. (1999)
Functional bowel disorders and functional abdominal
pain. Gut, 45, II43-II47. doi:10.1136/gut.45.2008.ii43
 Kienzle-Horn, S., Vix, J.M., Schuijt, C., Peil, H., Jordan,
C.C. and Kamm, M.A. (2007) Comparison of bisacodyl
and sodium picosulfate in the treatment of chronic con-
stipation. Current Medical Research and Opinion, 23,
 Kamm, M.A., Mueller-Lissner, S., Wald, A., Richter, E.,
Swallow, R. and Gessner, U. (2011) Oral bisacodyl is ef-
fective and well-tolerated in patients with chronic consti-
pation. Clinical Gastroenterology and Hepatology, 9,
 Müller-Lissner, S.A., Kamm, M.A., Scarpignato, C. and
Wald, A. (2005) Myths and misconceptions about chronic
constipation. American Journal of Gastroenterology, 100,
 Müller-Lissner, S.A. (1996) What has happened to the
cathartic colon? Gut, 39, 486-488.
 Kienzle-Horn, S., Vix, J.M., Schuijt, C., Peil, H., Jordan,
C.C. and Kamm, M.A. (2006) Efficacy and safety of bis-
acodyl in the acute treatment of constipation: A double-
blind, randomized, placebo-controlled study. Alimentary
Pharmacology & Therapeutics, 23, 1479-1488.
 Hinkel, U., Schuijt, C. and Erckenbrecht, J. (2008) OTC
laxative use of sodium picosulfate—Results of a phar-
macy-based patient survey (cohort study). International
Journal of Clinical Pharmacology and Therapeutics, 46,
Copyright © 2013 SciRes. OPEN ACCESS