Lactulose

BRAND NAMES

• Duphalac

• Enulose

• Generlac

• Kristalose

• Cephulac

MECHANISM OF ACTION

Lactulose is a non-absorbable sugar that works in the colon by being broken down into acids, which lower pH and trap ammonia as ammonium, reducing its absorption into the blood. It also pulls water into the bowel, softening stools and increasing bowel movements, which helps remove toxins from the body. It is commonly used in Hepatic encephalopathy and constipation.

PHARMACOKINETICS

Absorption

Lactulose is not absorbed in the small intestine because there are no enzymes to digest it. It passes unchanged into the colon, where bacteria ferment it into organic acids.

Distribution

For lactulose, the volume of distribution (Vd) is not applicable or not established (effectively ~0 L/kg) because it is minimally absorbed from the gastrointestinal tract and remains almost entirely within the intestinal lumen with negligible systemic distribution.

Metabolism

Lactulose is not metabolized by human enzymes. It is instead broken down in the colon by gut bacteria into low-molecular-weight organic acids such as lactic acid, acetic acid, and formic acid, which are responsible for its therapeutic effects.

Elimination

Lactulose is not significantly absorbed systemically, so it is eliminated mainly through the feces. In the colon, it is metabolized by gut bacteria into organic acids, and these products are also excreted in stool. A very small amount of unchanged drug or metabolites may be excreted in urine, but fecal elimination is the primary route.

PHARMACODYNAMICS

Lactulose is a non-absorbable disaccharide that acts locally in the colon. It is metabolized by colonic bacteria into organic acids, which lower the pH and create an osmotic effect. The acidic environment converts ammonia (NH₃) into ammonium (NH₄⁺), trapping it in the gut and reducing systemic absorption, thereby lowering blood ammonia levels.

ADMINISTRATION

Lactulose is administered orally as a syrup or solution for constipation and Hepatic encephalopathy. It can also be given via a rectal enema in patients who are unable to take it orally, especially in severe hepatic encephalopathy. The dose is usually adjusted based on clinical response, aiming for 2–3 soft stools per day in chronic therapy.

DOSAGE AND STRENGTH

Lactulose is commonly available as an oral solution with a strength of 10 g per 15 mL (66.7%) syrup. The dosage varies depending on the condition: for constipation, adults are usually started on 15–30 mL once or twice daily, adjusted to achieve 2–3 soft stools per day. For Hepatic encephalopathy, higher doses are used, often 25–30 mL 3–4 times daily, and may be titrated to produce regular bowel movements and reduce ammonia levels. In rectal administration (enema), different dosing schedules are used in severe cases under medical supervision.

DRUG INTERACTIONS

Lactulose has relatively few drug interactions because it is minimally absorbed, but it may reduce the effectiveness of oral medications that require colonic pH for absorption due to acidification of the gut. It can also increase the loss of potassium when used with diureticsor corticosteroids, potentially worsening electrolyte imbalance. Additionally, when used with antacids or non-absorbable antibiotics, its effect in treating Hepatic encephalopathy may be reduced or altered due to changes in gut pH and flora.

FOOD INTERACTIONS

Lactulose has no significant food interactions. Food may slightly delay its effect, but it does not reduce its action. Adequate fluids are recommended to support its laxative effect, especially in constipation and Hepatic encephalopathy.

CONTRAINDICATIONS

Lactulose is contraindicated in patients with intestinal obstruction (bowel obstruction), as it can worsen distension and complications. It should also be avoided in individuals with galactosemia, since it contains galactose and lactose derivatives that can be harmful in this condition. Caution is needed in patients with unexplained abdominal pain, nausea, or vomiting until a proper diagnosis is made.

SIDE EFFECTS

• Flatulence

• Abdominal bloating

• Abdominal cramps

• Diarrhea

• Nausea

• Dehydration (with high doses)

• Electrolyte imbalance (e.g., hypokalemia)

OVER DOSE

• Severe diarrhea

• Dehydration

• Electrolyte imbalance (especially hypokalemia and hypernatremia)

• Abdominal cramps and pain

• Excessive bowel movements

• Weakness and dizziness due to fluid loss

TOXICITY

Lactulose has very low toxicity because it is not significantly absorbed into the body. Problems mainly occur with overuse, leading to severe diarrhea, dehydration, and electrolyte imbalances such as low potassium levels. It may also cause weakness, dizziness, and abdominal discomfort, but it does not have a known direct lethal toxicity when used appropriately, including in conditions like Hepatic encephalopathy.