Lactulose

Lactulose is used in the treatment of:

• Constipation
• Hepatic Encephalopathy

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

A synthetic derivative of lactose; an ammonia detoxicant and laxative.1 2

Portal-Systemic Encephalopathy

Used as an adjunct to protein restriction and supportive therapy for prevention and treatment of portal-systemic encephalopathy (PSE), including hepatic pre-coma and coma.1

Useful in the management of PSE resulting from surgical portacaval shunts or chronic hepatic diseases such as cirrhosis.1

Reduces blood ammonia concentration, which usually leads to substantial improvement in patient’s mental state and EEG tracings.1

Does not alter the course of underlying liver disease and therefore does not obviate treatment of such disease or PSE.1

Since neomycin destroys bacteria and lactulose requires bacterial degradation for its effectiveness, concomitant therapy with these agents is theoretically counterproductive.1 (See Anti-infective Agents under Interactions.) However, some evidence suggests that concomitant therapy with lactulose and neomycin may be more effective than either drug alone.1

Not useful in the management of non-nitrogenous types of encephalopathy such as those induced by drugs or metabolic or electrolyte disturbances.1 Not effective in the treatment of coma associated with infectious hepatitis or other acute liver disorders.1

Chronic Constipation

Useful as a laxative in the treatment of chronic constipation in adults,2 including geriatric patients.1 Superiority compared with conventional laxatives not established.1

Used in the treatment of chronic constipation in children†; safety and efficacy in children not established.1

Used to restore regular bowel movements following hemorrhoidectomy†.1

Used to induce bowel evacuation in geriatric patients with colonic retention of barium and severe constipation following barium meal examination†.1

Administration

Administer orally, via gastric tube, or rectally.1 2

Oral Administration

When solution is administered orally, may minimize sweet taste by diluting with water, fruit juice, milk or by adding to food (e.g., desserts).1

When administering via gastric tube, dilute well to prevent induction of vomiting and possible aspiration pneumonia.1

For oral administration, reconstitute powder by dissolving contents of a 10- or 20-g packet in approximately 120 mL of water.1

Rectal Administration

May administer rectally to adults with PSE during stages of hepatic pre-coma or coma when the possibility of aspiration exists or when necessary endoscopic or intubation procedures interfere with oral administration.1

For rectal administration, dilute 200 g of powder in 700 mL of water or 0.9% sodium chloride solution and administer via a rectal balloon catheter.1

Dosage

Each 15 mL of commercially available lactulose solution provides approximately 10 g of the drug; corresponding doses provided by 2.5, 5, 7.5, 10, 30, 40, 45, 90, 150, and 300 mL of the commercial solution are approximately 1.67, 3.3, 5, 6.67, 20, 27, 30, 60, 100, and 200 g, respectively.1 Following reconstitution of the oral powder as directed, a 10- or 20-g dose is provided by administering the total volume.1

Pediatric Patients

Infants (limited data): Initially, 1.67–6.67 g daily in divided doses.1

Older children and adolescents: Initially, 27–60 g daily recommended by manufacturer.1

Adjust dosage every 1–2 days as necessary to produce 2–3 soft stools daily.1

If the initial dose produces diarrhea, reduce dose immediately; if diarrhea persists, discontinue drug.1

At least 5 g daily, usually given as a single dose after breakfast, has been used.1

Adults

20–30 g 3 or 4 times daily.1

Adjust dosage every 1–2 days as necessary to produce 2 or 3 soft stools daily.1 Usually dosage is 60–100 g daily; some patients may require higher dosage.1

Some clinicians recommend dosage adjustment according to acidity of colonic contents by measuring stool pH (with indicator paper) at initiation of therapy and adjusting dosage until stool pH is about 5.1 This pH is usually achieved when the patient has 2 or 3 soft stools daily during therapy.1

In the management of acute PSE episodes, give 20–30 g orally at 1- to 2-hour intervals to induce rapid laxation.1 When the laxative effect has been achieved, reduce dosage to the amount required to produce 2 or 3 soft stools daily.1

During treatment, improvement in patient’s clinical condition usually occurs within 1–3 days.1

Continuous long-term therapy with lactulose may decrease severity and prevent recurrence of PSE.1

For reversal of hepatic coma, 200 g is diluted with 700 mL of water or 0.9% sodium chloride solution and administered rectally via a rectal balloon catheter; solution is retained for 30–60 minutes.1

Retention enemas may be administered every 4–6 hours.1 If enema retained for <30 minutes, may repeat administration immediately.1

In some patients, reversal of hepatic coma may occur within 2 hours of the first enema.1 Before discontinuance of lactulose retention enemas, initiate recommended oral dosages of the drug.1

Usual initial dosage is 10–20 g daily.1 2 Dosage may be increased to 40 g daily if necessary.1

Following oral administration, 24–48 hours may be required to restore normal bowel movements.1

To facilitate bowel movements in patients undergoing hemorrhoidectomy†, administer 10 g twice daily on the day before surgery and twice daily for 5 days postoperatively.1

To induce bowel evacuation in geriatric patients with colonic retention of barium and severe constipation following barium meal examination†, 3.3–6.7 g twice daily for 1–4 weeks has been administered.1

Special Populations

Hepatic Impairment

No specific dosage recommendations for patients with hepatic impairment.1

Renal Impairment

No specific dosage recommendations for patients with renal impairment.1

Geriatric Patients

No specific dosage recommendations for geriatric patients.1

Contraindications

• Patients who require a low-galactose diet.1 2

Warnings/Precautions

Warnings

Administer with caution to patients who may require electrocautery procedures during proctoscopy or colonoscopy; the drug can cause accumulation of hydrogen gas in high concentrations, which in the presence of an electrical spark may theoretically result in an explosive reaction.1 Although such events have not been reported to date, patients receiving lactulose therapy should have a thorough bowel cleansing with a nonfermentable solution prior to these procedures.1 Insufflation of carbon dioxide may be used but probably is unnecessary.1

General Precautions

In the treatment of PSE, important to consider that serious underlying liver disease may produce complications such as electrolyte disturbances (e.g., hypokalemia) that require additional therapy.1 In addition, if diarrhea occurs, it may severely deplete fluids and potassium and may intensify symptoms of PSE.1 For these reasons, some clinicians recommend periodic determinations of serum potassium concentrations during long-term treatment with lactulose.1

Since lactulose solution contains some free lactose and galactose, the drug should be used with caution in patients with diabetes mellitus.1

Specific Populations

Category B.2

Not known if lactulose is distributed into milk.1 Use with caution in nursing women.1 2

Safety and efficacy for the treatment of chronic constipation in children not established.1 2

Determine serum electrolyte concentrations (e.g., potassium, chloride, carbon dioxide) periodically during therapy in geriatric, debilitated patients who receive lactulose for >6 months.1

Common Adverse Effects

Gaseous distention,1 belching,1 flatulence,1 2 borborygmi,1 abdominal discomfort (e.g., cramping).1 2 Dehydration and hyponatremia in infants.1

Absorption

Extent

Poorly absorbed from GI tract.1 2

Onset

Does not exert its effect until it reaches the colon.2

Extent

Less than 3% absorbed from small intestine following oral administration; negligible absorption from colon.1

Elimination

Metabolism

Absorbed drug not metabolized.1 Unabsorbed drug reaches colon unchanged, where it is metabolized by bacteria to form lactic acid and small amounts of acetic and formic acids.1

Elimination Route

Absorbed drug excreted in urine unchanged within 24 hours.1

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 Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Lactulose Solution 10 g/15 mL for Oral or Rectal Administration is available as follows:

16 fl oz (473 mL) bottle

64 fl oz (1893 mL) bottle

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

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 a 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

Distributed by:

Hi-Tech Pharmacal Co., Inc.

Amityville, NY 11701

Rev. 795:04 05/17

NDC 50383-795-16

Lactulose Solution, USP 10 g/15 mL

For oral or rectal administration

INDICATIONS AND DOSAGE: for the prevention and treatment of portal-systemic encephalopathy. See attached insert labeling for full information.

Rx only

16 fl oz (473 mL)

The bacterial degradation of lactulose resulting in an acidic pH inhibits the diffusion of NH3 into the blood by causing the conversion of NH3 to NH4+; also enhances the diffusion of NH3 from the blood into the gut where conversion to NH4+ occurs; produces an osmotic effect in the colon with resultant distention promoting peristalsis; reduces blood ammonia concentration to reduce the degree of portal systemic encephalopathy

Absorption

Poor

Metabolism

Via colonic flora to lactic acid and acetic acid; requires colonic flora for drug activation

Excretion

Primarily feces; urine (≤3%)

Subclinical (minimal) hepatic encephalopathy

Evidence-based guidelines and randomized, controlled trials confirm the effectiveness of lactulose in the treatment of subclinical hepatic encephalopathy. If diarrhea develops, the drug should be stopped and reinstituted at a lower dose.

Adverse events have not been observed in animal reproduction studies. Lactulose is poorly absorbed following oral administration. Use of dietary fiber or bulk-forming laxatives along with increased fluid intake is generally considered first line therapy for treating constipation in pregnant women. Short-term use of lactulose is also considered to be safe/low risk when therapy is needed; however, side effects may limit its use (Cullen, 2007; Mahadevan, 2006; Prather, 2004; Wald, 2003).

Applies to lactulose: oral powder and solution

Side effects include:

Gaseous distention, belching, flatulence, borborygmi, abdominal discomfort (e.g., cramping). Dehydration and hyponatremia in infants.

Children: 0.7 to 2 g/kg/day (1 to 3 mL/kg/day) orally in divided doses daily; generally recommended not to exceed the adult maximum of 40 g/day (60 mL/day).