What is the proper dosing of lactulose (a laxative medication)?

From the Guidelines

Lactulose should be dosed at 20-30 g orally 3-4 times per day for the management of overt hepatic encephalopathy, with the goal of achieving at least 2 bowel movements per day. The dosing of lactulose should be titrated to maintain two to three soft stools per day, as stated in the 2020 guidelines for liver cirrhosis 1. This approach is supported by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, which recommend initiating lactulose at a dose of 25 mL every 1-2 hours until bowel movements occur, then adjusting to 15-45 mL three to four times daily to maintain 2-3 soft stools daily 1.

For adults with constipation, lactulose can be dosed at 10-20 g (15-30 mL or 1-2 packets) daily, with the option to increase to 40 g (60 mL or 2-4 packets) daily if needed, as per the American Gastroenterological Association-American College of Gastroenterology clinical practice guideline 1. However, the primary goal in hepatic encephalopathy is to achieve the desired bowel movement frequency to reduce ammonia absorption.

Key points to consider when dosing lactulose include:

• The medication should be taken with a full glass of water or juice to improve palatability
• Dose adjustments should be made gradually based on clinical response
• Improvement in constipation typically occurs within 24-48 hours of starting treatment
• Common side effects include bloating, flatulence, abdominal cramping, and diarrhea if overdosed
• Lactulose works by drawing water into the intestinal lumen through osmosis and by being metabolized by colonic bacteria to produce acids that stimulate colonic motility, which helps reduce ammonia absorption in hepatic encephalopathy.

It is essential to monitor patients for signs of overdose, such as severe diarrhea, and adjust the dose accordingly. Additionally, lactulose can be administered via nasogastric tube if patients are unable to take medications orally, and enemas with lactulose 200 g and 700 mL water can be performed 3-4 times per day in severe cases 1.

From the FDA Drug Label

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 may be adjusted every day or two to produce 2 or 3 soft stools daily The dose of lactulose for this purpose is the same as the recommended daily dose On the basis of information available, the recommended 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.

The dosing of lactulose is as follows:

• Adults: 2 to 3 tablespoonfuls (30 mL to 45 mL, containing 20 grams to 30 grams of lactulose) three or four times daily.
• Pediatric:
  • Infants: 2.5 mL to 10 mL in divided doses.
  • Older children and adolescents: 40 mL to 90 mL daily. The dose may be adjusted to produce 2 or 3 soft stools daily 2.

From the Research

Dosing of Lactulose

• The dosing of lactulose is not explicitly stated in the provided studies, but its effectiveness in treating hepatic encephalopathy (HE) is compared to other treatments such as polyethylene glycol (PEG) and rifaximin 3, 4, 5.
• A study comparing lactulose to PEG found that PEG significantly decreased the time needed for resolution of HE and shortened the hospital stay 3.
• Another study found that the combination of lactulose and rifaximin was more effective than lactulose alone in treating overt HE 4.
• A review of long-term management of HE with lactulose and/or rifaximin found that lactulose is effective for preventing overt HE recurrence over the long term, and the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization 6.
• A randomized clinical trial comparing lactulose to PEG found that PEG led to more rapid HE resolution than standard lactulose therapy 5.

Treatment Options for Hepatic Encephalopathy

• Current treatment options for HE include lactulose, rifaximin, and PEG, which target factors such as ammonia toxicity, systemic inflammation, oxidative stress, and gut microbiota imbalance 4, 6, 5, 7.
• A multipronged approach to treating HE may be beneficial due to its complex pathogenesis 7.
• Emerging therapies that target these factors are being developed to provide more treatment options and preventive care interventions for HE 7.