Lactulose is a synthetic disaccharide used primarily as an osmotic laxative and for the management of hepatic encephalopathy . It is classified as a category B drug in pregnancy, indicating no evidence of risk in human studies.
Formulation
Lactulose is available as a syrup or oral solution, typically containing:
- >62% w/v lactulose
- Minor sugars: lactose , galactose , epilactose , and fructose
- Preservatives for microbial control
Pharmacological Classification
- Chemical class: Synthetic disaccharide sugar (galactose + fructose)
- Therapeutic class:
- Osmotic laxative
- Ammonia reducer (used in hepatic encephalopathy)
Indications
- Chronic constipation – especially in elderly patients and children
- Hepatic encephalopathy – to reduce serum ammonia levels
- Adjunct therapy (less common use):
- In seizure disorders like Lennox-Gastaut syndrome and primary generalized tonic-clonic seizures , though this is not a standard or first-line indication.
Mechanism of Action
In Constipation
- Lactulose resists digestion in the small intestine due to absence of lactulase enzyme in humans.
- Reaches the colon unchanged , where it is metabolized by colonic bacteria into lactic acid , acetic acid , and formic acid .
- These acids:
- Lower colonic pH (acidify contents)
- Increase osmotic pressure , drawing water into the lumen
- Soften stool and stimulate peristalsis
In Hepatic Encephalopathy
- Acidification of the colon traps ammonia (NH₃) by converting it to ammonium (NH₄⁺) , which cannot be absorbed.
- Also accelerates colonic transit, decreasing time for ammonia absorption.
- Result: Reduced serum ammonia and improved mental status
Pharmacokinetics
- Onset of action: 24–48 hours
- Absorption: Minimal; remains in the GI tract
- Excretion: Trace amounts in urine; most excreted in feces after bacterial fermentation
Dosage and Administration
Adults:
- Constipation: 15–30 mL orally once or twice daily; max ~60 mL/day
- Hepatic Encephalopathy: 30–45 mL orally 3–4 times/day; titrate to achieve 2–3 soft stools daily
Children:
- 1–5 years: 2.5–10 mL twice daily
- 5–10 years: 10 mL twice daily
Retention enema (for hepatic encephalopathy):
- 300 mL lactulose in 700 mL NS
- Retain for 30–60 minutes , repeat q4–6h if needed
Side Effects
Common adverse effects include:
- Abdominal bloating and cramps
- Flatulence , belching
- Nausea , especially at high doses
- Diarrhea (with prolonged use) leading to:
- Hypokalemia
- Hypernatremia
- Dehydration
- Unpleasant taste may affect adherence
- Rare: Hyperglycemia , especially in diabetic patients
Contraindications
Avoid or use with caution in patients with:
- Intestinal obstruction
- Low-galactose or lactose-free diets
- Disaccharidase deficiency
- Known hypersensitivity to lactulose or excipients
Precautions
- Monitor electrolytes during prolonged use
- Use cautiously in diabetics (contains galactose/fructose)
- Risk of lactic acidosis in patients with ileus
- Can worsen dehydration in pediatric or elderly patients
Drug Interactions
Decreased efficacy with:
- Antacids
- Oral neomycin (both reduce colonic acidification)
- Sodium bicarbonate, calcium carbonate
- Citrate salts (e.g., sodium citrate)
Avoid administering other oral drugs within 1 hour of lactulose to minimize reduced absorption.
Diagnostic Use
Sugar Absorption Test
- Used to assess intestinal permeability
- Lactulose combined with mannitol or rhamnose helps detect mucosal damage in conditions like celiac disease
Lactulose Breath Test
- Measures hydrogen gas in breath after ingestion
- Assesses orofecal transit time and carbohydrate malabsorption
- Limited by lactulose's own effect on gut motility
Clinical Pearls
- First-line treatment for hepatic encephalopathy
- Helps reduce mortality and hospitalization in cirrhotics
- Safe in pregnancy (Category B)
- Titrate dose to stool consistency, not volume
- Avoid overuse due to risk of electrolyte imbalance
Alternatives
- Rifaximin (often used with lactulose in hepatic encephalopathy)
- Polyethylene glycol (PEG) – for chronic constipation
- Sorbitol – another osmotic laxative, less commonly used
Patient Education
- Encourage adequate fluid intake
- Expect delayed onset (24–48 hours)
- Inform about potential for gas and bloating
- Advise to report persistent diarrhea or cramps
