Lactulose

Indications

  • Constipation (see Constipation, [[Constipation]]): effect may not be seen until 24-48 hrs after drug administration
  • Hepatic Encephalopathy (see Hepatic Encephalopathy, [[Hepatic Encephalopathy]])
    • Lactulose is effective in hepatic encephalopathy, but does not improve mortality rate [MEDLINE]

Pharmacology

  • Lactulose (Disaccharide of Galactose + Fructose = Beta-Galactosidofructose) is Poorly Absorbed from the Gastrointestinal Tract and is Converted by Colonic Bacteria to Lactic Acid (and to a lesser degree, to acetic acid and formic acid)
    • Acidification of Colon Enhances Diffusion of Ammonia from Blood into the Colon
    • Acidification of Colon Enhances Conversion of Ammonia (NH3) into Ammonium Ion (NH4+): as the ammonium ionis non-absorbable, this prevents colonic absorption of ammonium ion (and other amines)
    • Cathartic Effect of Lactulose with Increased Stool Volume and Decreased Time for Ammonia Absorption: caused by the osmotic effect of the organic acid metabolites of lactulose
      • Expulsion of ammonium ions and other nitrogenous substances from the colon
      • Increased fecal nitrogen excretion
    • Modification of Colonic Flora, Resulting in Displacement of Urease-Producing Bacteria with Non-Urease-Producing Bacteria
    • Reduced Formation of Potentially Toxic Short-Chain Fatty Acids (Propionate, Butyrate, Valerate)
    • Increased Incorporation of Ammonia by Colonic Bacteria: for synthesis of nitrogenous compounds

Potential Drug Interactions

  • Neomycin (see Neomycin, [[Neomycin]]): although neomycin may theoretically deplete the intestinal bacteria that metabolize lactulose, this concern is probably not relevant (as lactulose + neomycin may be synergistic when used together in the treatment of hepatic encephalopathy)
  • Non-Absorbable Antacids: concomitant use of non-absorbable antacids (which raise colonic pH) may inhibit the activity of lactulose

Metabolism

  • Absorbed Lactulose: absorbed lactulose is excreted unchanged in the urine within 24 hrs

Administration

  • PO: 30 ml (20 g) q4-12hrs, titrated to 3-4 soft bowel movements per day
  • Enema: 300 ml (200 g) retained for 30-60 min with rectal balloon catheter, q4-6hrs

Dose Adjustment

  • Hepatic: not defined
  • Renal: not defined

Adverse Effects

Gastrointestinal Adverse Effects

  • Belching
  • Bloating/Flatulence
  • Cramping Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
  • Diarrhea (see Diarrhea, [[Diarrhea]])
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
  • Theoretical Risk of Explosion During Colonoscopic Electrocautery: no cases reported, mainly a theoretical concern (due lactulose-induced formation of large amounts of hydrogen gas)

Other Adverse Effects

  • Hypokalemia (see Hypokalemia, [[Hypokalemia]]): due to diarrhea
  • Hyponatremia (see Hyponatremia, [[Hyponatremia]]): observed mainly with lactulose use in infants

References

  • Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;(2):CD003044 [MEDLINE]
  • Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: 10.1002/hep.27210. Epub 2014 Jul 8 [MEDLINE]