Lactulose
3.3g/5ml
Syrup
Drug
Category: Stimulant
Laxative / Osmotically acting laxatives.
Brand
Name: Duphalac
Pharmaceutical
Form and Composition
Lactulose
is an oral solution. It is a clear, viscous liquid, colorless to brownish
yellow. Lactulose oral solution does not contain any excipients, but may
contain small amounts of related sugars (e.g. lactose, galactose, epilactose, and
fructose) derived from the route of synthesis.
Pharmacodynamics
In
the colon lactulose is broken down by colonic bacteria into low-molecular
organic acids. These acids lead to a lowering of pH in the colonic lumen and
via an osmotic effect to an increase of the volume of the colonic contents.
These effects stimulate the peristalsis of the colon and return consistency of
the stools. The constipation is cleared and the physiological rhythm of the
colon is reinstated.
In
hepatic encephalopathy (HE), the effect has been attributed to suppression of
proteolytic bacteria by an increase of acidophilic bacteria (e.g.
lactobacillus) trapping of ammonia in the ionic form by acidification of the
colonic contents, catharsis due to the low pH in the colon as well as osmotic
effect, and alteration of the bacterial nitrogen metabolism by stimulating the
bacteria to utilize ammonia for bacterial protein synthesis.
Within
this context, however, it should be realized that hyperammonemia alone cannot
explain the neuropsychiatric manifestation of HE. The ammonia however might
serve as a model compound for other nitrogenous substances.
Lactulose
as a prebiotic substance strengthens the growth of health promoting bacteria,
like Bifidobacterium and Lactobacillus, whereas potentially pathogenic
bacteria, like Clostridium and Escherichia coli may be suppressed. This may
lead to a more favorable balance of the intestinal flora.
Pharmacokinetic
Properties
Lactulose
is poorly absorbed after oral administration and it reaches the colon
unchanged. There it is metabolized by the colonic bacterial flora. Metabolism
is complete at doses up to 25 – 50g or 40 -75ml; at higher dosages, a
proportion may be excreted unchanged.
Preclinical
Safety Data
The
results of acute, sub-chronic and chronic toxicity studies in various species
indicate that the compound has very low toxicity. The effects observed, appear
to be more related to the effect of bulk in the gastrointestinal tract than to
a more specific toxic activity.
In
reproduction and teratology experiments in rabbits, rats or mice no adverse
effects were found.
Therapeutic
Indications
For Constipation: regulation of the physiological
rhythm of the colon. Indicated where a soft stool is considered of medical
benefit (hemorrhoids, post colonic/anal surgery). Hepatic Encephalopathy (HE): treatment and prevention of hepatic coma or
precoma.
Administration
and Dosage
Lactulose
solution may be administered diluted or undiluted.
A
single dose of lactulose should be swallowed in one and should not be kept in
mouth for an extended period of time. The dose should be adjusted according to
the individual needs of the patient. In case of single daily dose, this should
be taken at the same time, e.g. during breakfast. During the therapy with
laxatives it is recommended to drink sufficient amounts of fluids (1.5 – 2 liters,
equal to 6 – 8 glasses) during the day. Dosing in constipation or where a
soft stool is considered of medical benefit. It may be given as a single
daily dose or is two divided doses; in bottles the measuring cup may be used. After
a few days the starting dosage may be adjusted to the maintenance dose based
upon treatment response. Several days (2 – 3 days) of treatment may be needed
before treatment effect occurs.
The
following dose is given:
Adult and adolescents: Starting daily dose 15 – 45ml.
Maintenance daily dose 15 – 30ml.
Children (7 – 14years): Starting daily dose 15ml. Maintenance
daily dose 10 - 15ml.
Children (1 – 6years): Starting daily dose 5 – 10ml.
Maintenance daily dose 5 - 10ml.
Infants under 1 year: Starting daily dose up to 5ml.
Maintenance daily dose up to 5ml.
Dosing
in HE (for adults only)
Starting
dose: 3 to 4 times daily 20 – 30g or 30 – 45ml. This dose may be adjusted to
the maintenance dose to achieve 2 to 3 soft stools per day.
Pediatric
population
The
safety and efficacy in children (newborn to 18years of age) with HE have not
been established. No data are available.
Elderly
patients and patients with renal or hepatic insufficiency
No
special dosage recommendations exist, since systemic exposure to lactulose is
negligible.
Contraindications
- Hypersensitivity to the active substance or
to any of the ingredients.
-
Galactosemia
-
Gastrointestinal obstruction, digestive perforation or risk of digestive
perforation.
Special
Warnings and Precautions for use
Consultation
of a physician is advised in case of:
-
Painful abdominal symptoms of undetermined cause before the treatment are
started.
-
Insufficient therapeutic effect after several days.
Lactulose
should be administered with care to patients who are intolerant to lactose.
The
dose normally used in constipation should not pose a problem for diabetics. The
dose used in the treatment of HE is usually much higher and may need to be
electrolyte balance.
Chronic
use of unadjusted doses and misuse can lead to diarrhea and disturbance of the
electrolyte balance.
This
product contains lactose, galactose and small amounts of fructose. Therefore,
patients with the rate hereditary problem of galactose or fructose intolerance,
the Lapp lactase deficiency or glucose-galactose malabsorption should not take
this medicine.
Pediatric
Population
Use
of laxatives in children should be exceptional and under medical supervision.
It should be taken into account that the defecation reflex could be disturbed
during the treatment.
Pregnancy
No
effects during pregnancy are anticipated, since systemic exposure to lactulose
is negligible.
Lactation
No
effects on the breastfed newborn/infant are anticipated, since the systemic
exposure of the breast-feeding woman to lactulose is negligible. Lactulose can
be used during breast-feeding.
Fertility
No
effects are to be expected, since systemic exposure to lactulose is negligible.
Effects
on ability to drive and use machines
Lactulose
has no or negligible influence on the ability to drive and use machines.
Undesirable
Effects
Flatulence
may occur during the first few days of treatment. As a rule it disappears after
a few days. Abdominal pain and vomiting may occur, as well as, nausea.
When
dosages higher than instructed are used, abdominal pain and diarrhea may occur.
In such a case the dosage should be decreased.
If
high doses (normally only associated with hepatic encephalopathy, HE) are used
for an extended period of time, the patient may experience an electrolyte
imbalance due to diarrhea.
Drug
Interaction
Do
not use with any other gastrokinectic drugs or other laxatives. Concomitant use
may lead to severe diarrhea.
Overdose
If
the dose is too high, the following may occur:
Symptom:
diarrhea and abdominal pain.
Treatment:
cessation of treatment or dose reduction. Extensive fluid loss by diarrhea or
vomiting may require correction of electrolyte disturbances.
Shelf
life
3
years
Storage
condition
Store
at temperatures not exceeding 25oC
