What is the recommended dose of lactulose for constipation and hepatic encephalopathy?

Lactulose Dosing for Constipation and Hepatic Encephalopathy

For hepatic encephalopathy, lactulose should be administered at 30-45 mL (20-30 g) every 1-2 hours initially until the patient has at least 2 bowel movements per day, then titrated to maintain 2-3 soft stools daily. 1, 2

Dosing for Hepatic Encephalopathy

Initial Dosing

• For acute hepatic encephalopathy (HE), start with 30-45 mL (20-30 g) of lactulose every 1-2 hours orally until at least 2 soft bowel movements are produced daily 1
• The FDA recommends hourly doses of 30-45 mL to induce rapid laxation in the initial phase of therapy for portal-systemic encephalopathy 2
• European guidelines specifically recommend 25 mL of lactulose syrup every 1-2 hours until at least two soft or loose bowel movements per day are produced 1

Maintenance Dosing

• After initial response, titrate to 20-30 g (30-45 mL) administered 3-4 times daily to maintain 2-3 soft stools per day 1, 2
• The FDA-approved maintenance dose is 2-3 tablespoonfuls (30-45 mL, containing 20-30 g of lactulose) three or four times daily 2
• Dose should be adjusted every 1-2 days to achieve the target of 2-3 soft stools daily 2

Rectal Administration

• For patients with severe HE (West-Haven criteria grade 3 or more) or those unable to take oral medications:
  • Administer 300 mL lactulose mixed with 700 mL water as an enema 3-4 times daily 1
  • Retention time should be at least 30-60 minutes for optimal effect 1, 2
  • Cleansing enemas containing soap or alkaline agents should be avoided 2

Dosing for Constipation

• For constipation, the FDA recommends the same dosing as for hepatic encephalopathy: 2-3 tablespoonfuls (30-45 mL) three or four times daily, adjusted to produce 2-3 soft stools daily 2
• Clinical improvement may occur within 24-48 hours, but sometimes takes longer 2

Special Populations

Pediatric Dosing

• For infants: 2.5-10 mL daily in divided doses 2
• For older children and adolescents: 40-90 mL total daily dose 2
• As with adults, the goal is to produce 2-3 soft stools daily 2

Monitoring and Adjustments

• Titrate dose to achieve 2-3 soft stools daily 1, 2
• If diarrhea develops, reduce the dose immediately 2
• If diarrhea persists despite dose reduction, discontinue lactulose 2

Important Considerations and Pitfalls

• Overuse of lactulose can lead to complications including aspiration, dehydration, hypernatremia, severe perianal skin irritation, and may even precipitate HE 1
• It is a misconception that lack of effect from smaller amounts of lactulose should be remedied with much larger doses 1
• When lactulose must be temporarily discontinued due to diarrhea, rifaximin (400 mg three times daily or 550 mg twice daily) can be used as an alternative 3
• Clinical studies have shown that lactulose leads to recovery in 70-90% of HE patients 1

Mechanism of Action

• Lactulose reduces intestinal pH through bacterial degradation to acetic and lactic acids 1
• It increases lactobacillus count, which do not produce ammonia 1
• Converts ammonia to ammonium, making it less absorbable 1
• Produces an osmotic laxative effect that helps eliminate ammonia 1, 4