Lactulose

Usage

• Lactulose is prescribed for the treatment of constipation and the prevention and treatment of portal-systemic encephalopathy (PSE), including hepatic encephalopathy, a complication of liver disease.
• Pharmacological classification: Lactulose is an osmotic laxative. In the context of hepatic encephalopathy, it can also be classified as ammonia-reducing agent.
• Mechanism of Action: For constipation, lactulose exerts an osmotic effect in the colon, drawing water into the lumen, softening the stool, and increasing stool volume, thereby promoting bowel movements. For hepatic encephalopathy, lactulose is metabolized by colonic bacteria to lactic acid and acetic acid, lowering the pH of the colon. This acidic environment favors the conversion of ammonia (NH3) to ammonium (NH4+), which is poorly absorbed and subsequently eliminated in the stool, reducing blood ammonia levels.

Alternate Names

• International or regional variations: Lactulose is a generic name recognized internationally.
• Brand names: Several brand names exist, including Constulose, Enulose, Generlac, Kristalose, and Duphalac.

How It Works

• Pharmacodynamics: Lactulose exerts its laxative effect by increasing osmotic pressure in the colon, resulting in increased water retention and stool softening. In hepatic encephalopathy, the acidification of the colon traps ammonia in its non-absorbable ammonium form, facilitating its removal.
• Pharmacokinetics: Lactulose is poorly absorbed after oral administration. It reaches the colon largely unchanged, where it is metabolized by intestinal bacteria. The small amount of lactulose that may be absorbed is excreted in urine. It is not metabolized by CYP enzymes. Elimination is primarily through fecal excretion.
• Mode of Action: Lactulose’s action involves altering the colonic microenvironment, both osmotically and through pH modification.
• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Lactulose does not bind to receptors, inhibit enzymes, or modulate neurotransmitters in its primary mechanisms of action for constipation and hepatic encephalopathy.

Dosage

Standard Dosage

Adults:

• Constipation: Initially, 15-45 mL (10-30 g) orally per day, as a single dose or in two divided doses. The dose may be adjusted to 15-30 mL (10-20 g) daily for maintenance, aiming for 2-3 soft stools per day.
• Hepatic Encephalopathy: Initially, 30-45 mL (20-30 g) orally 3-4 times per day. The dose can be titrated to achieve 2-3 soft stools per day.

Children:

• Constipation:
  • Infants (<1 year): 2.5-10 mL/day orally divided into doses.
  • Children (1-6 years): 5-10 mL/day orally.
  • Children (7-14 years): Initially 15 mL/day, adjustable to 10-15 mL/day for maintenance.
  • Older children (>14 years): Adult dose.
• Hepatic Encephalopathy: Limited data is available. Dosing is individualized to achieve 2-3 soft stools per day.

Special Cases:

• Elderly Patients: No specific dosage adjustments are typically recommended, but start at the lower end of the dosage range and titrate carefully.
• Patients with Renal Impairment: No specific dosage adjustments are required based on current guidelines.
• Patients with Hepatic Dysfunction: Dosage is adjusted based on the severity of encephalopathy and clinical response.
• Patients with Comorbid Conditions (e.g., diabetes): Monitor blood glucose closely, especially with higher doses used for hepatic encephalopathy.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Dosage adjustments are based on the specific clinical context and determined by the treating physician, aiming for 2-3 soft stools per day or targeting a specific blood ammonia level.

Dosage Adjustments:

• Dosage is adjusted based on individual response, targeting 2-3 soft stools daily.

Side Effects

Common Side Effects:

• Flatulence, abdominal cramping, bloating, distension, nausea, vomiting, diarrhea (with excessive doses).

Rare but Serious Side Effects:

• Severe diarrhea leading to electrolyte imbalances, particularly hypokalemia.

Long-Term Effects:

• Electrolyte imbalances with prolonged, excessive use.

Adverse Drug Reactions (ADR):

• Severe electrolyte imbalances, colonic dilatation (rare).

Contraindications

• Galactosemia, intestinal obstruction or subocclusive syndromes, acute inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease), existing or at risk of gastrointestinal perforation, painful abdominal syndromes of unknown cause, patients requiring a low galactose diet.

Drug Interactions

• Antacids: May inhibit the desired pH-lowering effect of lactulose.
• Antibiotics: May alter the intestinal flora and affect lactulose metabolism.
• Other Laxatives: Concurrent use may increase the risk of diarrhea and electrolyte imbalances.
• Medications affecting potassium levels: Lactulose may exacerbate hypokalemia caused by diuretics, corticosteroids, or amphotericin B.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category B (animal studies have not demonstrated fetal risk, but no adequate human studies are available. Use only if clearly needed).
• Breastfeeding: Lactulose is not expected to pass into breast milk in significant amounts due to its minimal systemic absorption. Use with caution.

Drug Profile Summary

• Mechanism of Action: Osmotic laxative, ammonia reduction via colonic acidification.
• Side Effects: Flatulence, abdominal cramps, distension, nausea, diarrhea.
• Contraindications: Galactosemia, bowel obstruction, acute IBD, GI perforation.
• Drug Interactions: Antacids, antibiotics, other laxatives.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: Stool frequency and consistency, blood ammonia levels (for hepatic encephalopathy), electrolytes.

Popular Combinations

• Lactulose is sometimes used in combination with neomycin or rifaximin for hepatic encephalopathy.

Precautions

• Evaluate for underlying causes of constipation or abdominal pain before initiating therapy.
• Monitor electrolytes, particularly potassium, during long-term use or in patients at risk of electrolyte imbalances.
• Use cautiously in patients with diabetes, lactose intolerance, or Roemheld syndrome.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lactulose?

A: See detailed dosage guidelines above.

Q2: How long does it take for Lactulose to work for constipation?

A: Onset of action for constipation is typically 24-48 hours.

Q3: What are the common side effects of Lactulose?

A: Flatulence, abdominal cramping, bloating, and diarrhea are common side effects.

Q4: Can Lactulose be used in pregnant or breastfeeding women?

A: Use with caution during pregnancy and breastfeeding if benefits outweigh risks.

Q5: What should I do if a patient experiences severe diarrhea while taking Lactulose?

A: Discontinue Lactulose and monitor electrolytes, especially potassium. Provide supportive care as needed for dehydration.

Q6: Does Lactulose interact with any other medications?

A: Yes, it can interact with antacids, antibiotics, and certain other laxatives. See the drug interactions section above.

Q7: Can Lactulose be used long-term?

A: Yes, it can be used long-term for the management of chronic constipation. Monitor electrolytes during prolonged use.

Q8: Is Lactulose absorbed systemically?

A: Lactulose is minimally absorbed. It primarily acts locally in the colon.

Q9: How is Lactulose administered for hepatic encephalopathy?

A: It can be given orally or rectally (as an enema) for hepatic encephalopathy. The oral route is preferred.