Lactulose - Lactulose solution prescribing information
INDICATIONS AND USAGE
For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.
Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns. The clinical response has been observed in about 75% of patients, which is at least as satisfactory as that resulting from neomycin therapy. An increase in patients’ protein tolerance is also frequently observed with lactulose therapy. In the treatment of chronic portal-systemic encephalopathy, lactulose has been given for over 2 years in controlled studies.
DOSAGE AND ADMINISTRATION
Oral
Adult: The usual adult, oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL, containing 20 grams to 30 grams 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 30 mL to 45 mL of lactulose solution 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.
Pediatric: 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 2 or 3 soft stools daily. On the basis of information available, the recommended initial daily oral dose in infants is 2.5 mL to 10 mL in divided doses. For older children and adolescents the total daily dose is 40 mL to 90 mL. If the initial dose causes diarrhea, the dose should be reduced immediately. If diarrhea persists, lactulose should be discontinued.
Rectal
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 soap suds 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 30 to 60 minutes. Lactulose enema may be repeated every 4 to 6 hours. If this lactulose 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.
CONTRAINDICATIONS
Since lactulose solution contains galactose (less than 1.6 g/15 mL) it is contraindicated in patients who require a low galactose diet.
ADVERSE REACTIONS
Precise frequency data are not available.
Lactulose may produce gaseous distention with flatulence or belching and abdominal discomfort such as cramping in about 20% of patients. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia. Nausea and vomiting have been reported.
To report SUSPECTED ADVERSE REACTIONS, contact Apozeal Pharmaceuticals Inc. at 1-833-688-7848 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DESCRIPTION
Lactulose is a synthetic disaccharide in solution form for oral or rectal administration. Each 15 mL of lactulose solution contains 10 grams lactulose (and less than 1.6 grams galactose, less than 1.2 grams lactose, and 0.1 grams or less of fructose).
Lactulose is a colonic acidifier for treatment and prevention of portal-systemic encephalopathy.
The chemical name for lactulose is 4-O-β-D-galactopyranosyl-D-fructofuranose. It has the following structural formula:
The molecular weight is 342.30. It is freely soluble in water.
CLINICAL PHARMACOLOGY
Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy. These actions are considered to be results of the following:
Bacterial degradation of lactulose in the colon acidifies the colonic contents.
This acidification of colonic contents results in the retention of ammonia in the colon as the ammonium ion. Since the colonic contents are then more acid that the blood, ammonia can be expected to migrate from the blood into the colon to from the ammonium ion.
The acid colonic contents converts NH 3 to the ammonium ion (NH 4 ) + ,trapping it and preventing its absorption.
The laxative action of the metabolites of lactulose then expels the trapped ammonium ion from the colon.
Experimental data indicate that lactulose is poorly absorbed. Lactulose given orally to man and experimental animals resulted in only small amounts reaching the blood. Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.
When incubated with extracts of human small intestinal mucosa, lactulose was not hydrolyzed during a 24-hour period and did not inhibit the activity of these extracts on lactose. Lactulose reaches the colon essentially unchanged. There it is metabolized by bacteria with the formation of low molecular weight acids that acidify the colon contents.
HOW SUPPLIED
Lactulose Solution, USP, 10 g/15 mL is a clear, colorless to pale brownish-yellow viscous, unflavored solution supplied in 8 fl oz (237 mL) NDC # 83745-249-08, 16 fl oz (473 mL) NDC # 83745-249-16 and 32 fl oz (946 mL) NDC # 83745-249-32 bottles.
Lactulose Solution contains: 667 mg lactulose / mL (10 g/15 mL).
Store between 15° to 30°C (59° to 86°F). 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.
Rx Only
Manufactured by: APOZEAL PHARMACEUTICALS INC. 2091 Hartel St Levittown, PA 19057
Made in USA
Revised 11/2024
