LACTULOSE SOLUTION, USP

Lactulose is a synthetic disaccharide in solution form for oral administration. Each 15 mL of lactulose solution contains; 10 g lactulose (and less than 1.6 g galactose, less than 1.2 g lactose, and 1.2 g or less of other sugars). Also contains water. The pH range is 4.8 to 6.0.

Lactulose is a colonic acidifier which promotes laxation.

The chemical name for lactulose is 4-O-β-D-galactopyranosyl-D-fructofuranose. The molecular formula is C₁₂H₂₂O₁₁. It has the following structural formula:

The molecular weight is 342.30. It is freely soluble in water.

Lactulose is poorly absorbed from the gastrointestinal tract and no enzyme capable of hydrolysis of this disaccharide is present in human gastrointestinal tissue. As a result, oral doses of lactulose reach the colon virtually unchanged. In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents. This in turn causes an increase in stool water content and softens the stool.

Since lactulose does not exert its effect until it reaches the colon, and since transit time through the colon may be slow, 24 to 48 hours may be required to produce the desired bowel movement.

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.

For the treatment of constipation. In patients with a history of chronic constipation, lactulose solution therapy increases the number of bowel movements per day and the number of days on which bowel movements occur.

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

A 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 H₂ 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 CO₂ as an additional safeguard may be pursued but is considered to be a redundant measure.

Precise frequency data are not available.

Initial dosing may produce flatulence and intestinal cramps, which are usually transient. 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 Akorn Operating Company LLC at 1-800-932-5676 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Signs and Symptoms

There have been no reports of accidental overdosage. In the event of overdosage, it is expected that diarrhea and abdominal cramps would be the major symptoms. Medication should be terminated.

Oral LD50

The acute oral LD₅₀ of the drug is 48.8 mL/kg in mice and greater than 30 mL/kg in rats.

Dialysis

Dialysis data are not available for lactulose. Its molecular similarity to sucrose, however, would suggest that it should be dialyzable.

The usual dose is 1 to 2 tablespoonfuls (15 to 30 mL, containing 10 g to 20 g of lactulose) daily. The dose may be increased to 60 mL daily if necessary. Twenty-four to 48 hours may be required to produce a normal bowel movement.

Note: Some patients have found that lactulose solution may be more acceptable when mixed with fruit juice, water or milk.

Lactulose Solution, USP 10 g/15 mL is available as follows:

8 fl oz (237 mL) bottle

16 fl oz (473 mL) bottle

32 fl oz (946 mL) bottle

15 mL unit dose in trays of 10 cups

30 mL unit dose in trays of 10 cups

Lactulose solution contains lactulose 667 mg/mL (10 g/15mL).

Store at controlled room temperature 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 30°C (86° F) 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 original container or in a tight, light-resistant container as defined in the USP, with a child-resistant closure.

Rx only

Distributed by:

Akorn Operating Company LLC

Gurnee, IL 60031

Rev. 779:08 06/22

NDC 50383-779-16

Lactulose Solution, USP

10 g/15 mL

INDICATIONS: For the treatment of constipation. See attached insert labeling for full information.

Rx only

16 fl oz (473 mL)

Delivers 30 mL

NDC 50383-357-30

LACTULOSE SOLUTION, USP 20g/30 mL

Indications: For the treatment

of constipation. See Insert.

Rx ONLY

Delivers 15 mL

NDC 50383-356-15

LACTULOSE SOLUTION, USP 10g/15 mL

Indications: For the treatment

of constipation. See Insert.

Rx ONLY