What is the recommended dose of L-ORNITHINE (L-Ornithine) L-Aspartate injection?

L-Ornithine L-Aspartate Injection Dosing

For hepatic encephalopathy in adults with cirrhosis, administer L-ornithine L-aspartate intravenously at 20-40 grams per day, infused continuously over 24 hours or divided into multiple infusions throughout the day. 1

Standard Dosing Regimen

The evidence supports dose-dependent efficacy, with higher doses showing superior ammonia-lowering effects:

• 20 grams per day: Prevents postprandial hyperammonemia after the second protein load and increases urea production rate 1
• 40 grams per day: Prevents postprandial hyperammonemia after both protein loads, significantly reduces plasma ammonia levels, and demonstrates the most robust ammonia-lowering effect 1
• Lower doses (5 grams per day): Insufficient to prevent postprandial ammonia elevation and not recommended for therapeutic use 1

Administration Protocol

Infusion method:

• Administer as continuous 24-hour infusion or divide into multiple 8-hour infusions throughout the day 1
• When using divided dosing, infuse over 8 hours during periods when protein intake occurs 1
• The drug can be given during daytime hours (e.g., 09:00-17:00) to coincide with meal times and postprandial ammonia peaks 1

Duration of therapy:

• For chronic hepatic encephalopathy: 14 consecutive days has been studied and shown effective 2
• Therapy duration should be guided by clinical response and ammonia levels 2, 3

Clinical Context and Efficacy

The rationale for these doses is based on ammonia metabolism:

• L-ornithine L-aspartate stimulates both urea cycle activity and glutamine synthesis, the two key pathways for ammonia detoxification 3, 4
• Doses of 20-40 grams demonstrate measurable increases in urea production rate, confirming pharmacological activation of ammonia clearance 1
• The 40-gram dose shows the most consistent prevention of hyperammonemia across all protein loading conditions 1

Important caveat: While research demonstrates beneficial effects on ammonia levels and hepatic encephalopathy symptoms with these doses 2, 4, the overall quality of evidence is very low due to methodological limitations in available trials 4. However, the drug has shown good safety and tolerability at these doses with no serious adverse events reported 2.

Monitoring Parameters

During infusion, monitor:

• Plasma ammonia levels every 2 hours initially to assess response 1
• Blood glucose and insulin levels, as the 40-gram dose can cause hyperglycemia and hyperinsulinemia 1
• Clinical signs of hepatic encephalopathy improvement 2, 3
• Urine output over 24 hours 1

Oral Dosing Alternative

For oral administration (when IV route is not feasible):

• 18 grams per day divided into three doses (6 grams three times daily) has been studied for chronic hepatic encephalopathy 2
• Administer at fixed times to prevent postprandial ammonia increases 2
• Oral formulation shows efficacy in reducing fasting and postprandial ammonia concentrations 2