Lactulose: Osmotic laxative for constipation and hepatic encephalopathy

Lactulose is a synthetic, non-absorbable disaccharide composed of galactose and fructose. Well-known brand names include Bifiteral, Lactulose AL, Lactulose Stada and Duphalac. On /wirkstoff/lactulose you will find the detailed pillar page with the international spelling.

In everyday use, lactulose is encountered as a sweetish-tasting syrup or powder. Patients typically use it for chronic constipation, while in clinical settings lactulose is the standard treatment and prevention of hepatic encephalopathy in liver cirrhosis. This dual role makes lactulose one of the most frequently prescribed gastrointestinal medications in Germany.

Mechanism of action

Lactulose is not split or absorbed in the small intestine because the human digestive system lacks the necessary disaccharidase. It therefore reaches the colon unchanged, where bacteria (especially bifidobacteria and lactobacilli) ferment it into short-chain fatty acids such as lactic acid, acetic acid and butyric acid.

Three effects explain the clinical action. First, the resulting acids osmotically bind water in the intestinal lumen, the stool becomes softer and more voluminous, and peristalsis increases. Second, the acids lower the pH in the colon. Ammonia (NH3) from protein metabolism is protonated to ammonium (NH4+) and can hardly pass through the intestinal wall anymore, so less nitrogen returns to the blood. Third, the acidic, carbohydrate-rich environment promotes the growth of saccharolytic bacteria over proteolytic ones, which further reduces ammonia formation. These effects explain both the laxative and ammonia-lowering action.

Indications

• Chronic and acute constipation: suitable for adults, children, pregnant women and nursing mothers
• Hepatic encephalopathy: treatment and secondary prophylaxis in liver cirrhosis, standard according to DGVS and EASL guidelines
• Stool softener after perianal procedures, for hemorrhoids, anal fissures
• Irritable bowel syndrome with constipation: as an option alongside macrogol
• Geriatric patients: opioid-induced constipation, immobility-induced constipation

Dosage and administration

Constipation in adults: initially 15 to 45 ml syrup per day, then maintenance 15 to 30 ml. The effect occurs after one to two days. Children up to six years: 5 ml/day, with gradual adjustment. Infants: start with 1 to 3 ml/day.

Hepatic encephalopathy: acutely 30 to 45 ml three times daily by mouth, target is two to three soft bowel movements per day. In comatose patients, administer as rectal lactulose enema 300 ml in 700 ml water, every 4 to 6 hours, until patient is responsive.

Diabetes mellitus: lactulose is not sugar-free, but contains only small amounts of fermentable substrate for hyperglycemia and is considered applicable for diabetics. A galactose load should be avoided in galactosemia.

Side effects

Common: flatulence, abdominal cramps, nausea, especially in the first few days or with rapid dose escalation. With proper dose titration, these symptoms usually resolve within a week.

Occasional to rare: diarrhea with electrolyte disturbances (hypokalemia, hypernatremia) with overdose, dehydration in elderly people with reduced fluid intake, allergic reactions.

Important: lactulose is contraindicated in galactose intolerance, hereditary fructose intolerance, glucose galactose malabsorption or mechanical ileus. If mechanical ileus is suspected, consult a physician.

Drug interactions

• Antibiotics (neomycin, rifaximin): can reduce lactulose fermentation and thus dampen the ammonia-lowering effect, but the combination is often deliberately used in hepatic encephalopathy since the overall effect outweighs this
• Gastric acid blockers (PPIs, H2 blockers): no direct pharmacokinetic conflict, but altered acid buffering can modify effects
• Other laxatives: additive effect, diarrhea risk
• Potassium-wasting diuretics: risk of hypokalemia increases

Special notes

Pregnancy and lactation: lactulose is considered the first-choice agent for pregnant women with constipation, as it is not absorbed and does not pass into breast milk.

Onset of action: patients should be aware that lactulose acts more slowly than stimulants (bisacodyl, senna). Too rapid dose escalation typically leads to flatulence without significant additional effect.

Hepatic encephalopathy as therapeutic goal: the aim is not the strongest possible diarrhea, but two to three soft bowel movements per day. Overdosing with profuse diarrhea increases the risk of dehydration and electrolyte shifts, which in turn can worsen encephalopathy.

Taste: some patients find the syrup unpleasantly sweet. It is better tolerated when diluted in water or juice.

You may also be interested in

• Lactulose, international spelling with detailed main page
• Lactolose, common spelling variant
• Macrogol, alternative osmotic laxative (PEG)
• Bisacodyl, stimulating laxative
• Rifaximin, non-absorbable antibiotic for hepatic encephalopathy

Frequently asked questions

Sources

• Gelbe Liste, Lactulose drug profile
• AWMF S2k guideline chronic constipation and DGVS guideline liver cirrhosis
• BfArM, Federal Institute for Drugs and Medical Devices
• EASL Clinical Practice Guidelines, hepatic encephalopathy