Lactulose

Lactulose is a synthetic disaccharide of galactose and fructose that is not digested or absorbed in the small intestine. It acts as an osmotic laxative in the colon and as an ammonia-lowering agent in hepatic encephalopathy.

Classification. Osmotic laxative; ammonia-lowering agent.

Mechanism. Colonic bacteria ferment lactulose to short-chain fatty acids, lowering faecal pH, increasing osmotic load and stool water, and stimulating peristalsis. Acidification traps ammonia as ammonium in the colon and promotes its faecal loss.

Pharmacodynamics. Laxative effect begins 24 to 48 hours after the first dose. Gas production causes bloating and flatulence early in treatment.

Pharmacokinetics. Less than 3% is absorbed and is excreted unchanged in urine. The rest reaches the colon and is degraded by bacteria.

Adult oral doses unless stated. Product concentration is usually 3.35 g in 5 mL (10 g in 15 mL).

Chronic constipation.

• Start 15 mL (10 g) twice daily, adjusted to produce one soft stool daily.

• Maintenance often 10 to 15 mL twice daily.

• Maximum 60 mL (40 g) daily.

• Allow 2 to 3 days for the full effect before increasing the dose.

• Usually combined with a stimulant laxative for opioid-induced constipation.

Hepatic encephalopathy (treatment and secondary prevention).

• Acute: 30 to 45 mL (20 to 30 g) every 1 to 2 hours until a soft stool is produced.

• Then titrate: 15 to 45 mL (10 to 30 g) two to three times daily to give 2 to 3 soft stools daily.

• Continue after recovery as secondary prevention, usually with rifaximin added for recurrence.

• Retention enema where oral route is not possible: 300 mL lactulose in 700 mL water or sodium chloride 0.9%, retained for 30 to 60 minutes, repeated every 4 to 6 hours.

Paediatric constipation.

• Age 1 month to 11 months: 2.5 mL twice daily.

• Age 1 to 4 years: 2.5 to 10 mL twice daily.

• Age 5 to 17 years: 5 to 20 mL twice daily.

• Adjust to response; macrogol is usually preferred first-line in children.

Kidney and liver adjustment. No adjustment. In cirrhosis, titrate to stool frequency rather than dose.

Contraindications. Galactosaemia; intestinal obstruction; gastrointestinal perforation or risk of perforation; hypersensitivity.

Common adverse effects. Flatulence, bloating, abdominal cramps, nausea and diarrhoea, which usually settle after a few days.

Serious adverse effects.

• Dehydration, hypernatraemia and hypokalaemia with excessive diarrhoea, particularly in hepatic encephalopathy, where volume depletion can precipitate encephalopathy and kidney injury.

• Aspiration in a patient with reduced consciousness when given orally; use a nasogastric tube or enema.

• Toxic megacolon with underlying severe colitis (rare).

Major interactions.

• Other laxatives: loose stool makes titration unreliable.

• Antacids may reduce effectiveness in hepatic encephalopathy by raising colonic pH.

• Neomycin and other antibiotics may alter the colonic flora and reduce the effect on faecal pH.

• Diuretics and corticosteroids: additive hypokalaemia.

Special groups.

• Pregnancy: not absorbed; compatible and preferred when bulk-forming laxatives fail.

• Breastfeeding: not excreted in meaningful amounts; compatible.

• Children: dose by age; macrogol preferred.

• Older adults: monitor fluids and electrolytes.

• Diabetes: contains small amounts of sugars (galactose, lactose); has little effect on glucose but check in unstable diabetes.

• Kidney impairment: no adjustment.

• Liver impairment: first-line for hepatic encephalopathy.

• Regional: inexpensive and widely available; the main option for hepatic encephalopathy where rifaximin is unavailable.

Formulations. Oral solution 3.35 g in 5 mL (some markets 10 g in 15 mL); powder sachets; enema preparation.

Administration. Take with or without food. May be mixed with water, juice or milk to mask the sweet taste. Take with a full glass of fluid.

Baseline. Hydration status; electrolytes in hepatic encephalopathy.

Monitoring.

• Stool frequency and consistency; target 1 soft stool daily for constipation and 2 to 3 soft stools daily for hepatic encephalopathy.

• Sodium, potassium and kidney function in repeated high-dose use.

• Mental state and flapping tremor in hepatic encephalopathy.

Therapeutic drug monitoring. Not applicable.

Stopping. Reduce the dose if diarrhoea exceeds 3 stools daily. In hepatic encephalopathy, do not stop without specialist input; stopping risks relapse.

Referral and escalation. Investigate constipation with red flags: weight loss, rectal bleeding, iron deficiency anaemia or change in bowel habit over age 50. Admit hepatic encephalopathy grade 2 or worse, or any case with a precipitant such as gastrointestinal bleeding or sepsis.