LACTULOSE AGD

Lactulose is a synthetic disaccharide derivative of lactose that is most commonly used as a laxative agent despite also being formally indicated to serve as an adjunct therapy in treating portal-systemic encephalopathy (PSE).

Label, 3, 4 Despite being first synthesized in 1929 1, investigations regarding its possible use as a laxative for the treatment of chronic constipation did not occur until the 1960s and its first clinical use for treating PSE was not until 1966.

Nevertheless, although lactulose received formal FDA approval in and has since become a readily available generic and brand-name non-prescription medication listed on the World Health Organization's List of Essential Medicines as one of the most effective and safe medicines employed in a health system 5, data regarding its optimal place in therapy is often ambiguous.

Especially considering the use of lactulose as a laxative is typically only considered after lifestyle and dietary modifications fail and the fact that lactulose therapy cannot be ethically withheld from patients diagnosed with PSE in a placebo study, the substance may just be one of many options available for treating constipation and its efficacy in managing PSE may never be formally confirmed or refuted via clinical investigation.

Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients.

Label, 3, 4 Additionally, lactulose is also employed as an adjunct to protein restriction and supportive therapy for the prevention and treatment of portal-systemic encephalopathy (PSE), including both the hepatic pre-coma and coma variations.

Label, 3, 4 In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis.

Moreover, there have also been studies demonstrating the capacity for lactulose to minimize the formation of gallstones and even some investigations regarding the experimental use of the agent in developing novel anticancer agents owing to its ability to bind galactin carbohydrates involved in various tumor progressions 4.

Lactulose formulations are most commonly administered via the oral route or the rectal route.

Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut.

Label, 3, 4 In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.

Evolved beta-galactosidase subunit alpha (Escherichia coli (strain K12)) Other.

After administration by the oral route, less than 3% of the given dose of lactulose solution is absorbed by the small intestine.

The remaining unabsorbed lactulose reaches the large intestine where it is metabolized.

• but even then, negligible quantities of unchanged lactulose or its metabolites are absorbed across the colon. 3, 4.

Negligible amounts of lactulose.

• metabolized or non-metabolized.

• are absorbed into the body.

Label, 3, 4.

Most lactulose that is administered subsequently remains predominantly around the gastrointestinal tract area.

Lactulose is essentially only metabolized in the colon by saccharolytic bacteria that are present there.

Label, 3, 4 In particular, the substance is broken down into lactic acid and small amounts of acetic and formic acid.

Label, 3, 4 Specific examples of bacteria that normally inhabit the large intestine that are capable of lactulose metabolism include Lactobacilli, Bacteroides, Escherichia coli, and Clostridia.

Hover over products below to view reaction partners Lactulose Acetic acid + Formic acid + Lactic acid.

The renal excretion of any lactulose that manages to be absorbed into the circulation has been determined to be 3% or less and is generally complete within 24 hours.

Any unabsorbed lactulose is largely excreted with stool.

The data regarding the half-life of lactulose is not readily available or accessible.

Negligible amounts of lactulose.

• metabolized or non-metabolized.

• are absorbed into the body.

Label, 3, 4.

Regardless, data regarding the clearance of lactulose is not readily available or accessible.

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It has been documented that the oral LD50 of lactulose is 48.8 mL/kg in mice and more than 30 mL/ kg in rats.

Label, 3, 4 It is expected that overdosage with lactulose would result in abdominal cramps and diarrhea, both of which should be treated with fluid and electrolyte replacement as required.

Label, 3, 4 Considering the use of lactulose during pregnancy in humans has not been formally investigated, the agent should only be used during pregnancy only when clearly needed.

Label, 3, 4 Similarly, it is unknown whether lactulose is distributed into human breastmilk.

Label, 3, 4 Use of the medication in nursing women should subsequently be undertaken with caution.

Label, 3, 4 Reproduction studies in rats, mice, and rabbits have not revealed any evidence of impaired fertility as a result of administering lactulose.

Label, 3, 4 Data regarding the safety and efficacy of using lactulose in children for the treatment of chronic constipation or portal-systemic encephalopathy (PSE) is either very limited or yet to be established.

Label, 3, 4 Information regarding the long-term mutagenic potential of lactulose solution in animals or humans and about the long-term carcinogenic potential in humans are not available.

theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy.

Accumulation of

H 2 gas in significant concentration in the presence of an electrical spark may result in an explosive reaction.

Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution.

Insufflation of

CO as an additional safeguard may be pursued but is considered to be a redundant measure.

Since lactulose solution contains galactose (less than 1.6 g/15 mL), it is contraindicated in patients who require a low galactose diet.

The usual adult, oral dosage is to 3 tablespoonfuls (30 to 45 ml, containing 20 g to 30 g of lactulose) three or four times daily.

The dosage may be adjusted every day or two to produce 2 or 3 soft stools daily.

Hourly doses of to 45 ml of Lactulose may be used to induce the rapid laxation indicated in the initial phase of the therapy of portal-systemic encephalopathy.

When the laxative effect has been achieved, the dose of lactulose may then be reduced to the recommended daily dose.

Improvement in the patient's condition may occur within 24 hours but may not begin before 48 hours or even later.

Continuous long-term therapy is indicated to lessen the severity and prevent the recurrence of portal-systemic encephalopathy.

The dose of lactulose for this purpose is the same as the recommended daily dose.

Very little information on the use of lactulose in young children and adolescents has been recorded.

As with adults, the subjective goal in proper treatment is to produce to 3 soft stools daily.

On the basis of information available, the recommended initial daily oral dose in infants is 2.5 to 10 ml in divided doses.

For older children and adolescents, the total daily dose is to 90 ml. If the initial dose causes diarrhea, the dose should be reduced immediately.

If diarrhea persists, lactulose should be discontinued.

When the adult patient is in the impending coma or coma stage of portal-systemic encephalopathy and the danger of aspiration exists, or when the necessary endoscopic or intubation procedures physically interfere with the administration of the recommended oral doses, lactulose solution may be given as a retention enema via a rectal balloon catheter.

Cleansing enemas containing soapsuds or other alkaline agents should not be used.

Three hundred ml of lactulose solution should be mixed with 700 mL of water or physiologic saline and retained for to 60 minutes.

Lactulose enema may be repeated every to 6 hours.

If the enema is inadvertently evacuated too promptly, it may be repeated immediately.

The goal of treatment is reversal of the coma stage in order that the patient may be able to take oral medication.

Reversal of coma may take place within 2 hours of the first enema in some patients.

Lactulose, given orally in the recommended doses, should be started before Lactulose by enema is stopped entirely.

USP, 10 g/15 ml, is a natural colored and an unflavored solution supplied in one pint (473 ml) bottles.

Lactulose solution, USP contains lactulose 670 mg/mL (10 g/15 mL).

Store between 36° to 86°F (2° to 30°C).

Do not freeze.

Under recommended storage conditions, a normal darkening of color may occur.

Such darkening is characteristic of sugar solutions and does not affect therapeutic action.

Prolonged exposure to temperatures above 86°F (30°C) or to direct light may cause extreme darkening and turbidity which may be pharmaceutically objectionable.

If this condition develops, do not use.

Prolonged exposure to freezing temperatures may cause change to a semi-solid, too viscous to pour.

Viscosity will return to normal upon warming to room temperature.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure.

Manufactured and packaged by

Fresenius Kabi Austria GmbH Estermannstraße 17 4020 Linz, Austria Manufactured for: Teva Pharmaceuticals Parsippany, NJ 07054 USA Revised – June 2022.

Teratogenic Effects Pregnancy category

Reproduction studies have been performed in mice, rats, and rabbits at doses up to 2 or 4 times the usual human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to lactulose.

There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when lactulose solution is administered to a nursing woman.

Very little information on the use of lactulose in pediatric patients has been recorded See DOSAGE AND ADMINISTRATION.