Devolac

Approved and Clinically Accepted Uses:

• Chronic Constipation:
  – Treatment of chronic idiopathic or functional constipation in adults and children.
  – Used when fiber supplementation or other laxatives are insufficient.
• Hepatic Encephalopathy (HE):
  – Management and prevention of portal-systemic encephalopathy, including hepatic coma.
  – Aims to reduce blood ammonia levels and improve cognitive function in liver disease.
• Off-Label Uses (Clinically Accepted):
  – Opioid-induced constipation: Used in resistant cases.
  – Pre-colonoscopy bowel preparation: Occasionally used as part of cleansing protocols.

Route of Administration: Oral or rectal

Adults – Chronic Constipation:

• Initial dose: 15–30 mL orally once daily
• Maintenance dose: 10–20 mL once daily
• Adjustment: Based on response; target is 1–2 soft stools per day

Children – Chronic Constipation:

• 1–5 years: 5 mL once daily
• 6–12 years: 5–10 mL once daily
• >12 years: Adult dosing applies
• May be mixed with juice, water, or milk

Adults – Hepatic Encephalopathy:

• Initial dose: 30–45 mL orally 3 to 4 times daily
• Titration: Adjust to achieve 2–3 soft stools per day
• Rectal administration (if oral route not possible):
  300 mL of lactulose in 700 mL of water or saline as a retention enema for 30–60 minutes

Elderly:

• No specific dose adjustment; monitor fluid and electrolyte status

Renal or Hepatic Impairment:

• No dose adjustment required

Lactulose is a synthetic disaccharide composed of galactose and fructose. It is not absorbed in the small intestine and passes unchanged into the colon, where colonic bacteria metabolize it into low-molecular-weight organic acids (e.g., lactic acid, acetic acid). These acids lower colonic pH and increase osmotic pressure, drawing water into the bowel to stimulate peristalsis, resulting in laxation. In hepatic encephalopathy, the acidic environment converts ammonia (NH₃) into ammonium (NH₄⁺), which is not absorbed, thereby reducing systemic ammonia levels and improving neurological symptoms.

• Absorption: Poorly absorbed in the gastrointestinal tract
• Distribution: Acts locally in the colon
• Metabolism: Fermented by colonic bacteria into lactic acid and other organic acids
• Excretion: Primarily excreted in feces; minor amounts excreted unchanged in urine
• Onset of action:
  – Constipation: 24 to 48 hours
  – Hepatic encephalopathy: variable, often within 12 hours
• Bioavailability: Not systemically bioavailable
• Half-life: Not applicable due to local gut activity

• Pregnancy:
  – FDA Category B
  – No evidence of harm in animal studies; limited human data
  – Generally considered safe during pregnancy for constipation or hepatic encephalopathy
• Lactation:
  – Safe for use during breastfeeding
  – Minimal systemic absorption; negligible excretion into breast milk
  – No reported adverse effects in breastfed infants
• Caution:
  – Use lowest effective dose
  – Monitor hydration status in prolonged use

• Primary Class: Osmotic Laxative
• Subclass: Non-absorbable synthetic disaccharide

• Hypersensitivity to lactulose or any component of the formulation
• Galactosemia
• Patients on a low-galactose diet
• Suspected or known gastrointestinal obstruction or perforation

• Electrolyte Imbalance:
  – Prolonged or high-dose use may cause hypokalemia, hypernatremia, or dehydration
• Diabetic Patients:
  – Contains sugars (e.g., galactose, lactose); monitor blood glucose as needed
• Severe Abdominal Symptoms:
  – Discontinue and assess for bowel obstruction if abdominal pain, vomiting, or bloating occurs
• Hepatic Encephalopathy:
  – Frequent monitoring required for stool frequency, ammonia levels, and neurological status

Common (GI system):

• Flatulence
• Abdominal bloating
• Nausea
• Diarrhea (especially with high doses)
• Cramping

Less Common:

• Electrolyte disturbances (hypokalemia, hypernatremia)
• Dehydration
• Rectal discomfort with enema use

Rare but Serious:

• Severe diarrhea with electrolyte imbalance
• Hyperosmolar states in vulnerable patients

Onset & Severity:

• Symptoms typically appear within the first 1–3 days
• Often mild and dose-dependent

• Antacids:
  – May reduce effectiveness by altering colonic pH
• Neomycin/Rifaximin (for HE):
  – May have synergistic effect in reducing ammonia
• Other laxatives:
  – Co-use may increase risk of dehydration and electrolyte loss
• Alcohol:
  – Concurrent use may worsen dehydration or hepatic dysfunction
• CYP450 interactions:
  – None known; not metabolized by CYP enzymes

• American Association for the Study of Liver Diseases (AASLD):
  – Lactulose remains first-line treatment for hepatic encephalopathy
• National Institute for Health and Care Excellence (NICE):
  – Recommends lactulose for chronic constipation when dietary measures fail
• European Society for Paediatric Gastroenterology (ESPGHAN):
  – Supports lactulose use in pediatric constipation, with appropriate dosing and monitoring

• Temperature: Store below 25°C (room temperature); do not freeze
• Humidity: Store in a dry environment
• Light Protection: Protect from direct light; keep in original packaging
• Handling Instructions:
  – Shake well before use (oral solutions)
  – Use within recommended period after opening
  – For powder: reconstitute as directed, refrigerate if instructed by manufacturer