L-Ornithine L-Aspartate + Pancreatin

A. Approved and Clinically Accepted Indications

• Chronic Liver Disease with Associated Digestive Enzyme Deficiency:
  Indicated for patients with chronic liver conditions such as cirrhosis, steatosis, or hepatitis, who also exhibit symptoms of exocrine pancreatic insufficiency (e.g., bloating, flatulence, indigestion, or steatorrhea).
• Hepatic Encephalopathy (Grade I–II):
  Used to reduce blood ammonia levels and improve cognitive function in patients with mild to moderate hepatic encephalopathy, particularly when coexisting with digestive dysfunction.
• Fatty Liver Disease (Alcoholic or Non-Alcoholic):
  Beneficial as a supportive therapy in managing elevated ammonia and improving nutrient absorption in patients with poor hepatic detoxification and impaired digestion.
• Post-Hepatic or Pancreatic Surgery Support:
  Supports liver detoxification and pancreatic enzyme replacement in post-surgical recovery.

Adults:

• Standard Oral Dose: 1–2 tablets or capsules three times daily, preferably after meals.
  Typical strength per dose:
• L-Ornithine L-Aspartate: 150–500 mg
• Pancreatin: 100–300 mg (standardized to lipase/amylase/protease activity)

Pediatrics:

• Not routinely recommended. Use only under pediatric hepatologist supervision if needed. Safety and efficacy data are limited.

Elderly:

• No dosage adjustment is required. Monitor liver and renal function periodically.

Renal Impairment:

• Use with caution. In patients with moderate to severe renal impairment, dose adjustment may be necessary due to potential nitrogen accumulation from L-Ornithine L-Aspartate.

Hepatic Impairment:

• Safe for mild to moderate hepatic dysfunction.
  For severe hepatic encephalopathy (Grades III–IV), parenteral L-Ornithine L-Aspartate is preferred.

Route of Administration:

• Oral, with meals. Tablets or capsules should be swallowed whole without crushing or chewing.

Duration of Therapy:

• As directed by a physician, depending on disease severity and symptom control. May be used long-term in chronic liver disease.

L-Ornithine L-Aspartate facilitates the detoxification of ammonia by enhancing the urea cycle in the liver (via ornithine) and promoting glutamine synthesis in peripheral tissues (via aspartate). This results in the conversion of ammonia to urea and glutamine, both of which are safely excreted, leading to a reduction in serum ammonia levels and improvement in neurocognitive symptoms associated with hepatic encephalopathy.

Pancreatin is a combination of digestive enzymes (lipase, amylase, and protease) derived from porcine pancreas. It compensates for pancreatic exocrine insufficiency by facilitating the breakdown and absorption of fats, carbohydrates, and proteins in the small intestine, thereby improving nutrient absorption and reducing symptoms like steatorrhea and bloating.

Together, the combination supports both ammonia detoxification and digestive enzyme replacement, making it suitable for liver patients with associated malabsorption.

L-Ornithine L-Aspartate:

• Absorption: Rapidly absorbed from the gastrointestinal tract.
• Distribution: Distributed to liver and skeletal muscle.
• Metabolism: Metabolized into urea (via ornithine) and glutamine (via aspartate).
• Elimination: Metabolic byproducts are excreted renally.
• Half-life: Not clinically significant due to rapid metabolic utilization.

Pancreatin:

• Absorption: Not systemically absorbed; acts locally in the intestinal lumen.
• Onset of Action: Begins digestion within 30 minutes after oral administration.
• Metabolism/Excretion: Degraded by intestinal proteases and eliminated through feces.

• Pregnancy:
  No adequate human studies exist. Animal data for individual components do not show teratogenic effects at therapeutic doses. Should be used in pregnancy only if clearly needed and prescribed by a physician.
• Lactation:
  Unknown whether components are excreted in breast milk. Use with caution in breastfeeding women. Monitor the infant for any signs of gastrointestinal disturbance.
• Recommendation: Use in pregnancy and lactation only under medical supervision due to limited safety data.

• Primary Class:
  Hepatic Detoxifier + Digestive Enzyme Supplement
• Subclasses:
• L-Ornithine L-Aspartate: Ammonia-lowering amino acid complex
• Pancreatin: Pancreatic enzyme replacement

• Known hypersensitivity to L-Ornithine, L-Aspartate, Pancreatin, or pork proteins
• Severe renal impairment (e.g., creatinine clearance <30 mL/min)
• Acute pancreatitis or flare-up of chronic pancreatitis
• Inborn errors of the urea cycle
• Pediatric use without medical supervision

• Renal Dysfunction: Monitor blood urea and creatinine. Adjust dose if nitrogen accumulation occurs.
• Pancreatic Disorders: Do not use during an acute episode of pancreatitis.
• Pork Protein Allergy: Pancreatin is of porcine origin; contraindicated in pork-allergic individuals.
• Liver Coma: In advanced hepatic coma, use IV L-Ornithine L-Aspartate as monotherapy.
• Monitoring: Regularly assess liver function, serum ammonia, and GI symptoms during prolonged use.

Common Side Effects:

• Gastrointestinal: Nausea, diarrhea, bloating, abdominal discomfort, flatulence
• Neurological (from LOLA): Headache, dizziness (rare)
• Skin: Mild rash or itching (rare)

Serious or Rare Side Effects:

• Pancreatin: High doses (especially in cystic fibrosis) may rarely cause fibrosing colonopathy or perianal irritation
• LOLA: Hyperazotemia in renal-impaired patients

Dose Dependency:

• GI effects are dose-related and reversible upon reducing the dose.
• Serious reactions are rare when used within the therapeutic range.

• Antacids (e.g., calcium carbonate, magnesium hydroxide): May reduce pancreatin efficacy by altering pH.
• Iron Supplements: May reduce enzyme activity; stagger administration.
• High-Protein Diets: May counteract ammonia-lowering effects of L-Ornithine L-Aspartate.
• CYP450 Interactions: Neither component significantly affects CYP450 enzymes.

• Hepatic Encephalopathy Guidelines (AASLD & EASL):
  L-Ornithine L-Aspartate is acknowledged as a second-line or adjunctive treatment for mild to moderate hepatic encephalopathy, especially when ammonia levels remain elevated despite lactulose therapy.
• Pancreatin Use:
  Widely accepted as first-line treatment for exocrine pancreatic insufficiency; no significant regulatory updates in this fixed-dose combination.
• No recent changes in indications, dosage, or black box warnings from FDA or EMA.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity and Light: Store in a dry place, protected from moisture and direct sunlight
• Handling: Do not crush or chew pancreatin tablets/capsules (especially if enteric-coated)
• Refrigeration: Not required
• Shelf Life: Use within the expiration date stated on the packaging