Lactulose - Drug Monograph

Introduction

Lactulose is a synthetic disaccharide analog used primarily for the treatment of constipation and hepatic encephalopathy. It is classified as an osmotic laxative and works by drawing water into the colon and acidifying colonic contents. First introduced in the 1960s, lactulose remains a cornerstone therapy for these conditions due to its efficacy and favorable safety profile.

Mechanism of Action

Lactulose exerts its effects through two primary mechanisms:

1. Osmotic action: As a non-absorbable disaccharide, lactulose remains intact in the small intestine and draws water into the bowel lumen through osmosis, increasing stool water content and softening fecal matter.

2. Acidification of colonic contents: In the colon, lactulose is metabolized by gut bacteria to low molecular weight organic acids (primarily lactic, acetic, and formic acids). This lowers colonic pH from approximately 7.0 to 5.0, which: - Creates an osmotic gradient that further draws water into the colon - Converts ammonia (NH₃) to ammonium (NH₄⁺), which is less readily absorbed - Promotes the growth of acidophilic bacteria that utilize ammonia - Reduces colonic transit time

Indications

• Treatment of chronic constipation
• Prevention and treatment of portal-systemic encephalopathy (hepatic encephalopathy)

• Management of irritable bowel syndrome (IBS)
• Prophylaxis of hepatic encephalopathy in cirrhotic patients
• Treatment of small intestinal bacterial overgrowth (SIBO)

Dosage and Administration

• Adults: 15-30 mL (10-20 g) orally once daily; may increase to 60 mL daily
• Children: 7.5 mL daily after breakfast; adjust based on response

• Initial: 30-45 mL orally 3-4 times daily
• Maintenance: Titrate to produce 2-3 soft stools daily
• Rectal administration: 300 mL diluted with 700 mL water or normal saline as retention enema

• Elderly: Start with lower doses due to increased sensitivity
• Renal impairment: No dosage adjustment required
• Hepatic impairment: Standard dosing for encephalopathy; monitor closely

Pharmacokinetics

Contraindications

• Known hypersensitivity to lactulose or any component of the formulation
• Patients requiring a low-galactose diet
• Conditions where increasing intestinal motility might be dangerous (e.g., intestinal obstruction, acute abdominal conditions)

Warnings and Precautions

• Electrolyte imbalance: May cause hypokalemia with prolonged use
• Dehydration: Monitor fluid status, particularly in elderly patients
• Hepatic encephalopathy: In overdose, may cause diarrhea and excessive fluid loss that could precipitate or worsen encephalopathy
• Diabetes: Contains galactose and lactose; use with caution in diabetic patients
• Pregnancy: Category B - Use only if clearly needed
• Lactation: Excreted in breast milk; use with caution

Drug Interactions

• Antacids: May reduce lactulose's effectiveness in acidifying colonic contents
• Non-absorbable antibiotics (e.g., neomycin): May interfere with bacterial metabolism of lactulose
• Other laxatives: Concurrent use may increase risk of dehydration and electrolyte abnormalities
• Oral medications: May theoretically affect absorption of other drugs due to accelerated transit time

Adverse Effects

• Flatulence (68%)
• Abdominal discomfort (30%)
• Nausea (14%)
• Cramping (10%)
• Diarrhea (5%)

• Electrolyte imbalances (hypokalemia)
• Dehydration
• Excessive bowel activity
• Vomiting

• Severe dehydration
• Intestinal obstruction (if impaction occurs)
• Hypernatremia (with concentrated solutions)

Monitoring Parameters

• For constipation: Bowel frequency, stool consistency, abdominal discomfort
• For hepatic encephalopathy: Mental status, number of bowel movements, stool pH
• Electrolytes: Particularly potassium and sodium with prolonged use
• Fluid status: Especially in elderly or debilitated patients
• Ammonia levels: In hepatic encephalopathy (though clinical status is more important)
• Glycemic control: In diabetic patients

Patient Education

• Take exactly as prescribed; do not exceed recommended dosage
• May be diluted with water, juice, or milk to improve taste
• Onset of action is typically 24-48 hours
• Report severe abdominal pain, nausea, vomiting, or watery diarrhea
• Maintain adequate fluid intake while taking this medication
• For hepatic encephalopathy: Report any changes in mental status or neurological function
• Store at room temperature; solution may darken with time but remains effective

References

1. Pharmaceuticals M. Lactulose package insert. 2021. 2. American Gastroenterological Association. Medical Position Statement: Constipation. Gastroenterology. 2013;144(1):211-217. 3. Blei AT, Córdoba J. Practice Parameters Committee of the American College of Gastroenterology. Hepatic Encephalopathy. Am J Gastroenterol. 2001;96(7):1968-1976. 4. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. 5. Lexicomp Online. Lactulose monograph. Wolters Kluwer Clinical Drug Information. 2023. 6. Micromedex Solutions. Lactulose drug information. Truven Health Analytics. 2023. 7. World Gastroenterology Organisation Global Guidelines. Constipation: A Global Perspective. 2010. 8. National Institute for Health and Care Excellence (NICE). Lactulose for constipation. 2022.