Lactitol: A Review of its Use in the Treatment of Constipation

International Journal of Recent Advances in Pharmaceutical Research

January 2012; 2(1): 1-5
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Lactitol: A Review of its Use in the Treatment of Constipation

*ARIF A.FARUQUI, CHANDRAKANT JOSHI

Medley Pharmaceuticals Ltd. Mumbai-93

Abstract

Constipation is a heterogeneous disorder with a wide spectrum of symptoms and complaints. Constipation is a highly
prevalent and bothersome disorder that negatively affects patients' social and professional lives and places a great
economic burden on patients. Osmotic laxatives are widely prescribed in the management of constipation due to their
superior efficacy, tolerability and safety in pediatric patients, during pregnancy and elderly population. Lactitol &
Lactulose are synthetic disaccharide osmotic laxatives. With its more pleasant taste, lactitol is better tolerated and more
palatable. This article reviews the pharmacological properties of lactitol, as well as clinical trials evaluating its role in
constipation. Data from comparative study with Lactulose shows that Lactitol offers superior efficacy, better tolerability
and palatability. Cathartic effect of Lactitol is more predictable. Lactitol appears to be the ideal successor to lactulose for
the treatment of constipation.

Keywords: Lactitol, Constipation, Lactulose

1.0. INTRODUCTION

Constipation is a highly prevalent and bothersome They fail to normalize bowel habit in up to 40% of
disorder that negatively affects patients' social and patients, and their use may be detrimental because
professional lives and places a great economic of exacerbation of other symptoms such as
burden on patients. Various epidemiological studies abdominal pain, bloating, or flatulence [3].
report the prevalence of constipation to be about
20% [1]. American College of Gastroenterology In patients unresponsive or intolerant to
(ACG) recently recommended an expanded fibre, both osmotic and stimulant laxatives are
definition of constipation: “Unsatisfactory effective, but the latter must be avoided for long
defecation characterized by infrequent stools, term use as they have a potential for adverse effects
difficult stool passage, or both. Difficult stool [4].
passage includes straining, a sense of difficulty
passing stool, incomplete evacuation, hard/lumpy Lactitol & Lactulose are synthetic
stools, prolonged time to stool, or need for manual disaccharide osmotic laxatives. With its more
maneuvers to pass stool. The ACG Chronic pleasant taste, lactitol is better tolerated and more
Constipation Task Force also clarified what is meant palatable. This article reviews the pharmacological
by chronic, stating that “Chronic constipation is properties of lactitol, as well as clinic trials
defined as the presence of these symptoms for at evaluating its role in constipation.
least 3 months [2]. Standard treatment includes
increasing the oral intake of fibre in the form of 1.1. Pharmacodynamics Properties
wheat bran or bulk forming agents. Although there
is some evidence from controlled trials confirming Lactitol (B-galactosido- sorbitol) monohydrate is a
their efficacy, these measures are often inadequate. disaccharide analogue of lactulose. It has been
widely used in the treatment of constipation &
____________________________________________________________ hepatic encephalopathy. Lactitol is sugar alcohol
used as replacement sweeteners and approved by
*Correspondence the US FDA as food additive. Lactitol is included in
United State National Formulary (USNF), European
Dr. Arif A. Faruqui, MD Pharmacopoeia 6th Ed, The United States
General Manager-Medical Services Pharmacopeia 31, 2008. Osmotic disaccharides
Medley Pharmaceuticals Ltd. laxatives cannot be digested in the small bowel; it
D-2, MIDC, Andheri (E), Mumbai-93 passes intact into the colon where bacteria ferment
Email: [email protected] it to lactic, formic and acetic acids. These organic
acids acidify the stool and obligate excretion of stool

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Arif & Chandrakant. Int J Recent Adv Pharm Res, 2012;2(1):1-5

ISSN: 2230-9306; www.ijrapronline.com

1

International Journal of Recent Advances in Pharmaceutical Research

January 2012; 2(1): 1-5
____________________________________________________________________________________________________________________________________________

water to the extent that these fermentation 1.4. Therapeutic Efficacy
products are not absorbed by the colon, increasing
the osmotic pressure in the intestinal lumen, The efficacy of Lactitol in the treatment of
resulting in an increase in faecal volume, thus constipation has been evaluated in various clinical
stimulate the peristalsis movement [5]. trials. Efficacy in constipation is established through
open non comparative trial and comparative studies
with lactulose and liquid paraffin.

1.5. Comparison with Lactulose

Figure 1: Lactitol Candiani C et al compared acceptability, efficacy and
tolerability of lactitol syrup in chronic or
1.2. Lactitol a prebiotic hospitalization-related constipation with lactulose
in 172 patients, ranging in age between 19 to 85
Lactitol is known as a prebiotic; it can increase the years. Dose of either product (lactitol & lactulose)
quantity of the beneficial bacteria and decrease the was 30 ml. Patient’s acceptability indicated the
population of putrefactive bacteria selectively, significant preference towards lactitol 73.2%
reduce the intestinal pH, and lower the production compared to lactulose 26.8%. The global efficacy
and absorption of ammonia. Lactitol significantly judgment expressed by the physicians was excellent
increases Bifidobacterium and Lactobacillus to high in 61.91% of patients compared to 47.83%
(Figure 1)[6]. of patients who received lactulose. Results favored
lactitol with regards to efficacy in the treatment of
1.3. Pharmacokinetic properties constipation [9].

Animal experiments and low-dose oral tolerance Hammer B et al compared the efficacy of
tests in normal subjects suggest that lactitol is not lactitol and lactulose in 57 ambulant patients
absorbed from the mammalian small intestine [7]. (lactitol group: 31; lactulose group: 26) with mean
The gastrointestinal absorption of lactitol has been age of 54 years. Lactitol was given at a dose of
studied in 6 healthy volunteers and 8 patients with 20 g/day for three days followed by the
cirrhosis. Following administration of lactitol 0.5 maintenance dose of 10 g/day for 25 days.
g/kg, no lactitol was found in serum. The urinary Lactulose was given at a dose of 20.1 g/day for
excretion of lactitol over 24 h ranged from 0.1 to three days followed by a maintenance dose of
1.4% of the administered dose (0.46% in cirrhotic 13.4 g/day for 25 days. The study was conducted
and 0.35% in healthy volunteers). Blood D- and L- for a period of four weeks. Frequency of BM (basal
lactate and plasma glucose did not increase movement) per week in the lactitol group was 6.7
following lactitol. ±4.39 and lactulose group was 7.4 ± 4.48.
Percentage of patients with ≥3.5 BM/week at the
The data indicate that lactitol was poorly end of study in lactitol group was 82%, and
absorbed from the gastrointestinal tract in healthy lactulose group was 81%. Seventy six percent of
volunteers and patients with cirrhosis, and that the patients with lactitol reported normal or soft stool
disaccharide did not disturb glucose or lactate compared to 67% of patients with lactulose
homeostasis [8]. (p=0.50).10(32%) patients in lactitol treated
reported adverse events as compared to 16 (61%)
in lactulose group (p=0.02) [10].

Heitland and Mauersberger conducted
randomized study in 60 participants. Lactitol
(n=30) and lactulose (n=30) was administered 20g
/day as single dose in patients suffering from
chronic constipation. Duration of therapy was 2
weeks. Frequency (BM/day) after 2 weeks
treatment with lactitol was 0.87, as compared to
lactulose 0.79 (0.05<p<0.1, n.s.). No significant

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Arif & Chandrakant. Int J Recent Adv Pharm Res, 2012;2(1):1-5

ISSN: 2230-9306; www.ijrapronline.com

2

International Journal of Recent Advances in Pharmaceutical Research

January 2012; 2(1): 1-5
____________________________________________________________________________________________________________________________________________

differences in consistency, side effects or other daily; routine laboratory tests at the beginning and
symptoms (bloating, flatulence, nausea, cramping, at the end of the trials. The results showed that the
and diarrhea) was reported [11]. subjects treated with lactitol have manifested,
besides a proved therapeutic efficacy, a better
Efficacy of lactitol and lactulose was tolerability and compliance than the subjects
compared in 60 elderly patients with the mean age treated with lactulose [14].
of 79 years; suffering from functional constipation
by Doffoel M et al. Lactitol was given at a dose of 1.7. Lactitol compared with Liquid paraffin
15 g/day and lactulose at a dose of 15 ml/day.
Frequency of BM in the lactitol group was 5.5 per The aim of this open and randomized clinical trial
week and lactulose group was 4.9 per week. 85 % was to compare, in terms of efficacy, lactitol with
percent of patients with lactitol reported normal petroleum jelly, regarding the time before recovery
stool consistency as compared to 83% of patients of intestinal transit in patients having undergone
with lactulose [12]. anal surgery. The main criterion for efficacy was the
time taken to obtain the first stool after surgery.
1.6. Efficacy in Pediatric population Lactitol appears to be more effective than
petroleum in terms of recovery of intestinal
51 children (23 males, 28 females) in the age group transit: the first postoperative stool was obtained
of 8 months to 16 years with chronic idiopathic 13 hours earlier with lactitol.
constipation were enrolled in the study. The
patients were divided into two groups: Group A: 19 Mean number of stools per day was
patients treated with lactitol (250-400 mg/kg/day); significantly higher with lactitol (p = 0.046), the
Group B: 23 patients treated with lactulose (500- daily dose could be-reduced for more patients
750 mg/kg/day). The study was conducted for a under lactitol on day 4 (p = 0.004) and, also on day
period of 30 days. There was a statistically 4, the general efficacy assessment was significantly
significant increase in stool frequency per week in favor of lactitol (p = 0.033).Tolerance was rated
after treatment with lactitol or lactulose (P <0.001). "good" by 97% of patients on day 7, and no
As compared to group A, group B patients statistically significant difference was observed for
complained abdominal pain (P <0.005) and any of the tolerability criteria. Lactitol therefore
flatulence (P <0.001) more frequently (62 % vs. 32 appears to be an interesting choice, with a high
%). In addition, patients treated with lactitol found benefit/risk ratio, in the treatment of the
it to be more palatable and had a better compliance transitory constipation frequently observed
as compared to lactulose. This study demonstrated immediately after anal surgery [15].
that lactitol, because of the less number of side
effects compared to lactulose, and should be 1.8. Non comparative study
considered as a useful agent in the treatment of
chronic idiopathic constipation in childhood [13]. To study clinical and biological tolerability, 114
chronically constipated patients of both sexes, aged
In another study, 39 children (18 males, 21 18-70, without any organic alteration of the colon,
females) suffering from intestinal stasis were received lactitol over a period of one or two months.
treated with lactitol or a reference drug (lactulose Clinical tolerability was found to be good by 80 % of
in crystalline form), according to a balanced patients and biological tolerability excellent. Clinical
randomization, for 15 days. The first group of efficacy was found correct for 80 per cent of
children included 19 subjects treated with lactitol; patients with a dosage of 20 g (single dose in the
the second group included 20 subjects treated with evening). All patients, except one, agreed with the
lactulose. The dosages of lactitol and lactulose were, packaging and the taste of the product [16].
respectively, of 150-350 mg/kg and of 150-300
mg/kg daily per os with a single administration in 1.9. Tolerability
the morning. For each patient the tested parameters
were: number of intestinal evacuations, consistency 10 patients in lactitol treated (32 %) reported
of stool and adverse reactions (abdominal swelling, adverse events as compared to 16 in lactulose
abdominal pain, nausea, vomiting, and meteorism) group 61 % (p=0.02) in a clinical study conducted in
57 adult patients. In another study no significant

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Arif & Chandrakant. Int J Recent Adv Pharm Res, 2012;2(1):1-5

ISSN: 2230-9306; www.ijrapronline.com

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International Journal of Recent Advances in Pharmaceutical Research

January 2012; 2(1): 1-5
____________________________________________________________________________________________________________________________________________

differences in consistency, side effects or other Lactulose is an osmotic laxative with
symptoms (bloating, flatulence, nausea, cramping, proven efficacy and tolerability. Poor compliance
and diarrhea) was reported [10]. and side effect has been reported with lactulose.
Poor compliance is due to excessively sweet taste
In pediatric patients more incidences of and gastrointestinal side effects such as bloating,
side effects have been reported with lactulose flatulence, and severe and unpredictable diarrhea
treatment. In one of study conducted in pediatric possibly leading to dehydration. Even after
population, as compared to lactitol, patients with prolonged usage its cathartic effects are not entirely
lactulose therapy complained abdominal pain predictable; therefore compliance with treatment
(P <0.005) and flatulence (P <0.001) more may be poor. Despite these disadvantages no
frequently (62 % vs. 32 %). In addition, patients analogues with more favorable physicochemical
treated with lactitol found it to be more palatable properties have been developed for use in this
and had a better compliance as compared to condition. But now lactitol is available in market
lactulose [13]. with some distinct advantage as compared to
lactulose.
1.10. Dosage and Administration

In the treatment of constipation, lactitol Data from comparative study with
monohydrate is given in an initial dose of 20 g daily Lactulose shows that Lactitol offers superior
as a single dose with the morning or evening meal, efficacy, better tolerability and palatability.
subsequently adjusted to produce one stool daily. A Cathartic effect of Lactitol is more predictable.
dose of 10 g daily may be sufficient for many Lactitol appears to be the ideal successor to
patients [17]. In pediatric population 250 to 400 lactulose for the treatment of constipation.
mg/kg/day dose is recommended.
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January 2012; 2(1): 1-5
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