When to discontinue lactulose and rifaximin (Rifaximin) therapy?

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Last updated: April 23, 2025View editorial policy

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From the Guidelines

Lactulose and rifaximin should be discontinued when the patient has recovered significant liver function and muscle mass, and the precipitating factors for hepatic encephalopathy have been controlled, as suggested by the 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 1. When considering discontinuation of these medications, it is essential to assess the patient's overall liver function and body habitus, as these factors significantly influence the risk of further bouts of overt hepatic encephalopathy (OHE) 1.

  • Key factors to consider when stopping lactulose and rifaximin include:
    • Control of recurrent precipitating factors, such as infections or variceal hemorrhages
    • Recovery of significant liver function and muscle mass
    • Normalization of mental status and ammonia levels
    • Presence of 2-3 soft bowel movements daily without diarrhea
  • It is crucial to monitor for recurrence of symptoms after discontinuation, as many patients with cirrhosis require indefinite therapy, particularly those who have experienced multiple episodes of encephalopathy 1.
  • A gradual tapering approach may be preferable to sudden discontinuation, especially for patients who have been on long-term therapy.
  • The decision to stop these medications should be individualized based on the patient's clinical response, underlying liver function, and presence of ongoing risk factors, with consideration of the potential for recurrence of hepatic encephalopathy, as indicated by tests positive for minimal hepatic encephalopathy (MHE) or covert hepatic encephalopathy (CHE) before stopping HE drug therapy 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Stopping Lactulose and Rifaximin

There is no clear evidence on when to stop lactulose and rifaximin treatment. However, the following points can be considered:

  • The treatment of hepatic encephalopathy (HE) with lactulose and/or rifaximin is generally long-term, with some studies suggesting that lactulose is effective for the prevention of overt HE recurrence over the long term 2.
  • The addition of rifaximin to lactulose has been shown to significantly reduce the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability 2, 3, 4.
  • Some studies suggest that combination therapy with rifaximin and lactulose may be more effective than lactulose alone in the treatment of overt HE 3, 4.
  • However, one study found that patients treated with lactulose only had a higher percentage of improvement in neurological status and lower mortality compared to those treated with lactulose and rifaximin 5.

Considerations for Stopping Treatment

  • The decision to stop lactulose and rifaximin treatment should be based on individual patient factors, such as the severity of HE, response to treatment, and presence of any adverse effects.
  • Patients with a lower grade of encephalopathy on admission may have a better outcome with lactulose only 5.
  • The use of rifaximin in combination with lactulose may provide additional benefits in terms of increased effective rate and decreased mortality than lactulose alone in patients with HE 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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