What is the recommended dosage of L-Ornithine L-Aspartate (LOLA) for the treatment of Hepatic Encephalopathy?

Recommended Dosage of L-Ornithine L-Aspartate (LOLA) for Hepatic Encephalopathy

For the treatment of hepatic encephalopathy, the recommended dosage of intravenous LOLA is 30 g/day. 1

Intravenous LOLA Administration

• Intravenous LOLA at 30 g/day has been shown to effectively lower plasma ammonia concentrations and improve hepatic encephalopathy symptoms 1
• When used in combination with lactulose, intravenous LOLA (30 g/day) leads to a lower grade of hepatic encephalopathy within 1-4 days of treatment (OR 2.06-3.04) and shorter duration until symptom recovery (1.92 vs. 2.50 days, p=0.002) compared to lactulose alone 1
• For patients with West-Haven criteria grade 1-2 hepatic encephalopathy, intravenous LOLA has been shown to lower number connection test (NCT)-A time and plasma ammonia concentrations more effectively than placebo 1

Oral LOLA Administration

• Oral LOLA can lower the NCT-A time and plasma ammonia concentrations, though further studies are required to fully assess its efficacy in managing overt hepatic encephalopathy 1
• In clinical trials, oral LOLA has been administered at doses of 18 g/day (divided into three doses) with demonstrated efficacy in reducing hyperammonemia and improving mental status in patients with cirrhosis and hepatic encephalopathy 2
• For prevention of postprandial hyperammonemia in conditional ornithine deficiency, lower doses of approximately 1 g/day may be sufficient 3

Mechanism of Action

• LOLA works by providing substrates (ornithine and aspartate) that are important for metabolizing ammonia to urea and glutamine 1
• This mechanism helps lower plasma ammonia concentrations, which produces improvements in hepatic encephalopathy symptoms 1
• Both amino acids play key roles in ammonia detoxification and in proline and polyamine biosyntheses 3

Clinical Considerations

• LOLA should be considered as part of a comprehensive treatment approach that may include lactulose (20-30 g orally 3-4 times per day) 4, 5
• For patients who cannot tolerate or do not respond adequately to lactulose, LOLA can be an effective alternative or adjunctive therapy 6
• LOLA appears to be most effective in more severe grades of hepatic encephalopathy 6

Safety Profile

• LOLA has demonstrated a favorable safety profile with minimal adverse events reported in clinical trials 2, 7
• A Cochrane review found that LOLA may have a potential benefit in reducing serious adverse events compared to placebo or no intervention, though the quality of evidence was very low 8
• When comparing LOLA to other treatments like lactulose, probiotics, or rifaximin, no significant differences in adverse events have been observed 8

Treatment Algorithm

1. For overt hepatic encephalopathy requiring intravenous therapy: Administer LOLA 30 g/day intravenously 1
2. For oral therapy: Consider LOLA 18 g/day in divided doses 2
3. Monitor clinical response through:
   • Assessment of mental status
   • Measurement of plasma ammonia levels
   • Number connection test performance 1
4. Consider combination therapy with lactulose for enhanced efficacy 1