From the Guidelines
Lactulose is the primary treatment for hepatic encephalopathy, with a recommended initial dose of 30-45 mL every 1-2 hours until the patient has at least 2 bowel movements a day, as it has been shown to lead to recovery in 70-90% of patients 1.
Mechanism of Action
Lactulose works by reducing intestinal pH through the production of acetic and lactic acids, increasing the count of lactobacillus, which do not produce ammonia, and converting ammonia to ammonium, making it less absorbable 1.
Dosage and Administration
The dose of lactulose should be titrated to achieve two to three soft stools per day, and if patients are unable to take medications orally, administration via nasogastric tube or enema may be considered 1.
Efficacy and Safety
Lactulose has been shown to be more effective in improving symptoms than placebo, with a relative risk of 0.62 (95% CI, 0.46-0.84) 1, and is generally well-tolerated, with common side effects including bloating, gas, and abdominal cramps 1.
Special Considerations
Patients with diabetes should use lactulose cautiously, as it contains galactose and lactose, and the medication should be stored at room temperature and can be mixed with water or juice to improve taste 1.
Clinical Practice
In clinical practice, lactulose can be considered for the treatment of constipation if symptoms have failed to improve with fiber and over-the-counter laxatives, and individuals do not experience significant bloating or abdominal pain with lactulose use 1.
From the FDA Drug Label
DESCRIPTION Lactulose is a synthetic disaccharide in solution form for oral or rectal administration. The usual adult, oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL, containing 20 grams to 30 grams of lactulose) three or four times daily.
The dosage of Lactulose is 20 grams to 30 grams orally, three or four times daily, for adults.
- The initial daily oral dose in infants is 2.5 mL to 10 mL in divided doses.
- For older children and adolescents, the total daily dose is 40 mL to 90 mL.
- Rectal administration is also possible, with a mixture of 300 mL of lactulose solution and 700 mL of water or physiologic saline, retained for 30 to 60 minutes 2, 2.
From the Research
Lactulose Overview
- Lactulose is considered the first-line therapeutic agent for treating hepatic encephalopathy 3
- The principal mechanism by which lactulose inhibits production of ammonia by coliform bacteria is through acidification of the gastrointestinal tract 3
- Lactulose is effective for the prevention of overt hepatic encephalopathy recurrence over the long term 4
Comparison with Other Treatments
- Rifaximin was generally found to be equal or superior to lactulose in clinical studies for treating hepatic encephalopathy 3
- The addition of rifaximin to lactulose significantly reduces the risk of overt hepatic encephalopathy recurrence and hepatic encephalopathy-related hospitalization, compared with lactulose therapy alone 4
- Polyethylene glycol (PEG) has been shown to be more effective than lactulose in reducing the average Hepatic Encephalopathy Scoring Algorithm (HESA) Score at 24 hours 5
Alternative Therapies
- Other medication therapies, such as probiotics, zinc, and flumazenil, have been studied as alternative options for patients unresponsive to or intolerant of traditional lactulose therapy 6
- Rifaximin has been effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy 3