Lactulose

Generic Name: Lactulose
Pharmacological Class: Osmotic laxative
Therapeutic Class: Laxative and ammonia-lowering agent
ATC Code: A06AD11
Legal Status: Prescription and over-the-counter (depending on country and indication)
Common Brand Names: Duphalac, Lactugal, Constulose, Enulose, Generlac
Formulations Available:
– Oral solution (commonly 3.3 g/5 mL or 10 g/15 mL)
– Crystals/powder for reconstitution
– Rectal enema (for hepatic encephalopathy)

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Mechanism of Action

Lactulose is a synthetic disaccharide composed of galactose and fructose that is not absorbed in the small intestine.

1. Laxative Effect (colon-based):

   • It reaches the colon intact, where it is metabolized by bacterial flora into low-molecular-weight organic acids (e.g., lactic acid, acetic acid).

   • These acids lower colonic pH, which:

     • Increases osmotic pressure

     • Draws water into the lumen

     • Softens stools and stimulates peristalsis

2. Ammonia Reduction (in hepatic encephalopathy):

   • Low pH traps ammonia (NH₃) as ammonium ion (NH₄⁺), which is poorly absorbed

   • Reduces serum ammonia levels

   • Alters gut microbiota to favor non-urease-producing species

   • Inhibits intestinal ammonia production and absorption

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Therapeutic Indications

1. Constipation (Chronic or Occasional):

   • Adults and pediatric patients

   • Particularly useful in elderly or post-operative patients

2. Hepatic Encephalopathy (HE):

   • Prevention and treatment of portal systemic encephalopathy

   • Management of chronic or episodic HE in patients with cirrhosis

   • Prevention of recurrent encephalopathic episodes

3. Other Off-Label Uses:

   • Prevention of post-operative ileus (under investigation)

   • Colonic cleansing (less common use)

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Dosage and Administration

Constipation (Oral Use)

Adults:

• Initial: 15–30 mL once daily or in divided doses

• Maintenance: 10–20 mL/day

• Dose adjusted based on response (2–3 soft stools per day desired)

Children:

• 1–5 years: 5 mL daily

• 6–12 years: 10 mL daily

• Infants (<1 year): 2.5 mL daily

• Dose titrated based on clinical response

Hepatic Encephalopathy (Oral Use)

Adults:

• Initial: 30–50 mL orally 3 times daily

• Dose adjusted to achieve 2–3 soft stools/day

• Long-term maintenance therapy often required

Pediatric Use:

• Only under specialist care

• Dose adjusted by weight and response

Rectal Administration (in coma or severe HE):

• 300 mL lactulose + 700 mL water or saline as enema

• Retained for 30–60 minutes

• Repeat every 4–6 hours until patient is responsive

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Pharmacokinetics

• Absorption: Not significantly absorbed from the GI tract

• Onset of action (constipation):

  • Oral: 24–48 hours

  • Rectal: within a few hours

• Onset in HE: Variable; serum ammonia may drop within 24–48 hours

• Metabolism: Colonic bacteria metabolize to short-chain fatty acids

• Excretion: Feces (as lactic, acetic acids); minimal systemic absorption

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Contraindications

• Known galactosemia

• Intestinal obstruction

• Conditions requiring low-galactose or lactose-free diets

• Suspected appendicitis (due to stimulation of peristalsis)

• Hypersensitivity to lactulose or formulation excipients

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Warnings and Precautions

1. Electrolyte Disturbance (especially in HE):

   • Prolonged diarrhea can lead to hypokalemia, hypernatremia, dehydration

   • Monitor serum electrolytes in long-term or high-dose therapy

2. Diabetes Mellitus:

   • Contains galactose and lactose

   • Oral solution may affect glycemic control in insulin-dependent diabetics

3. Lactose Intolerance:

   • Can cause bloating and abdominal discomfort

   • Contains small amounts of lactose

4. Avoid excessive dosing:

   • Overdosage may cause severe diarrhea and dehydration

   • Dose must be titrated gradually

5. Duration of Use:

   • If constipation persists >7 days without identifiable cause, reassess diagnosis

6. Caution in ileostomy/colostomy patients due to fluid balance risks

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Adverse Effects

Common (≥1%):

• Flatulence

• Abdominal cramps

• Bloating

• Diarrhea (dose-dependent)

• Nausea

Uncommon (0.1–1%):

• Vomiting

• Electrolyte imbalance (prolonged use)

• Headache

• Increased thirst

Rare (<0.1%):

• Allergic reactions (rash, pruritus)

• Hypernatremia

• Hypokalemia

• Metabolic acidosis (in prolonged diarrhea)

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Drug Interactions

Drug Class / Agent	Interaction
Antacids	May reduce efficacy by altering colonic pH
Neomycin or rifaximin	Synergistic effect in HE treatment
Other laxatives	Additive effect, risk of electrolyte loss
Oral drugs with narrow therapeutic index (e.g., digoxin)	Accelerated GI transit may reduce absorption
Warfarin	Diarrhea may affect vitamin K absorption → INR changes (monitor closely)

Pregnancy and Lactation

Pregnancy:

• FDA Category B / BNF Category A

• Not teratogenic in animal studies

• Considered safe for use in pregnancy for both constipation and HE

Lactation:

• Not significantly absorbed → compatible with breastfeeding

• No known adverse effects in nursing infants

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Patient Counseling Points

• May take 24–48 hours for full effect on constipation

• Take with water or juice to improve taste and tolerability

• Do not exceed prescribed dose to avoid diarrhea

• Store oral solution at room temperature; do not freeze

• Inform prescriber if symptoms persist beyond 7 days

• In hepatic encephalopathy, stool frequency (2–3/day) is the therapeutic target

• Can cause abdominal bloating or gas initially – usually transient

• Oral hygiene: Rinse mouth after taking the sweet solution to prevent dental caries in long-term users

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Comparison with Other Laxatives

Laxative Type	Example	Action Time	Suitability
Osmotic (non-saline)	Lactulose	24–48 hrs	Chronic constipation, HE
Osmotic (saline)	Magnesium hydroxide	2–6 hrs	Acute constipation
Bulk-forming	Psyllium	12–72 hrs	Chronic constipation
Stimulant	Senna, bisacodyl	6–12 hrs	Short-term use
Stool softener	Docusate	12–72 hrs	Mild constipation

Lactulose is slower in onset but suitable for long-term use, especially in elderly, liver failure, or chronic constipation settings.

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Monitoring Parameters

• Stool frequency and consistency (daily)

• Serum ammonia levels (in hepatic encephalopathy)

• Electrolytes (Na⁺, K⁺) during high-dose or prolonged therapy

• Hydration status in at-risk patients

• Blood glucose (if diabetic) due to sugar content

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Storage

• Store at room temperature (15–30°C)

• May become darker over time, which does not affect potency

• Do not freeze

• Use within 1–2 months of opening bottle