What is sodium phenylacetate used for? Understanding its crucial role in managing hyperammonemia

October 6, 2025 •

3 min read

Sodium phenylacetate, often administered in combination with sodium benzoate, is a critical medication for treating acute hyperammonemia, a life-threatening condition associated with urea cycle disorders. Affecting approximately 1 in 35,000 births, urea cycle disorders are genetic conditions that lead to a toxic buildup of ammonia in the blood if left untreated. This injectable medication provides an alternate pathway for nitrogen excretion, helping to lower and control ammonia levels and prevent serious neurological damage or death.

Quick Summary

Sodium phenylacetate is used as adjunctive therapy for treating acute hyperammonemia and encephalopathy in individuals with urea cycle enzyme deficiencies. It works by removing waste nitrogen, reducing toxic blood ammonia levels, and preventing neurological complications.

Key Points

Emergency Treatment: Sodium phenylacetate, often as Ammonul, is an adjunctive therapy for acute hyperammonemia in patients with urea cycle disorders.
Alternative Pathway: It functions as a 'nitrogen scavenger,' providing a non-urea cycle route for the body to eliminate waste nitrogen.
Dual Action: It is typically co-administered with sodium benzoate; phenylacetate conjugates with glutamine, while benzoate conjugates with glycine to aid nitrogen removal.
Careful Administration: The medication must be diluted and infused intravenously via a central venous catheter to prevent tissue damage and burns.
Side Effect Monitoring: Due to risks like neurotoxicity, electrolyte imbalance, and fluid overload, patients must be closely monitored during treatment.
Life-Threatening Condition: The medication is critical for preventing irreversible neurological damage, coma, or death associated with high blood ammonia levels.

The purpose and function of sodium phenylacetate

Sodium phenylacetate is primarily used as an emergency intervention to manage severe and acute episodes of hyperammonemia. This condition occurs when ammonia builds up to toxic levels in the blood, often due to genetic urea cycle disorders (UCDs) where the body cannot effectively convert ammonia to urea for excretion. High ammonia levels can rapidly cause brain damage, coma, or death, necessitating prompt treatment with medications like sodium phenylacetate. It acts as a 'nitrogen scavenger' by providing an alternative way for the body to remove waste nitrogen.

The mechanism of action: providing an alternate nitrogen pathway

Sodium phenylacetate helps patients with impaired urea cycle function by offering a metabolic bypass. After intravenous administration, it combines with glutamine in the liver and kidneys to form phenylacetylglutamine. This compound contains two nitrogen atoms and is easily excreted in the urine. The body replaces the used glutamine, effectively removing excess nitrogen and lowering blood ammonia.

The role of sodium benzoate in combination therapy

Sodium phenylacetate is usually given with sodium benzoate in a product called Ammonul. This combination provides a dual mechanism for removing waste nitrogen. While phenylacetate works with glutamine, sodium benzoate combines with glycine to produce hippuric acid. Hippuric acid contains one nitrogen atom and is also quickly excreted by the kidneys. This combined action helps to rapidly reduce dangerously high ammonia levels.

Administration of sodium phenylacetate

Given the critical nature of treating hyperammonemia, sodium phenylacetate is administered intravenously in a hospital setting with close medical supervision. It is essential to dilute the medication and infuse it through a central venous catheter, as peripheral administration can lead to severe tissue damage.

Administration typically involves:

Initial dose: An initial dose to quickly lower ammonia levels. Repeat initial doses are generally not recommended due to the risk of neurotoxicity from high phenylacetate levels.
Maintenance: A continuous infusion to maintain the ammonia-lowering effect until the patient's ammonia levels are stable and they can resume oral intake and medications.

This treatment is part of a broader strategy that includes dietary protein restriction, caloric support, and sometimes hemodialysis in severe cases to rapidly remove ammonia.

Potential risks and side effects

Sodium phenylacetate is vital for life-threatening hyperammonemia but carries risks requiring careful monitoring. Side effects can include metabolic issues like hyperglycemia and hypokalemia, neurological effects such as neurotoxicity and worsening encephalopathy, and other concerns like sodium overload and injection site reactions.

Comparison of sodium phenylacetate and sodium benzoate

Sodium phenylacetate conjugates with glutamine to form phenylacetylglutamine, removing two moles of nitrogen, while sodium benzoate conjugates with glycine to form hippuric acid, removing one mole of nitrogen. The metabolite from benzoate is eliminated faster than that from phenylacetate. Neurotoxicity risk is higher with prolonged high levels of phenylacetate, while benzoate generally has a lower toxicity risk at therapeutic levels.

Conclusion

To summarize, what is sodium phenylacetate used for? Its primary role is in the emergency treatment of acute hyperammonemia, particularly in individuals with urea cycle disorders. Combined with sodium benzoate, it effectively lowers toxic ammonia levels by creating an alternative route for nitrogen removal, thereby preventing severe neurological damage. Due to the potency of the medication and potential side effects, administration requires careful technique and close patient monitoring. While crucial in emergencies, it is part of a broader treatment plan for urea cycle disorders that includes ongoing management strategies such as dietary protein restriction. For more detailed information, see DailyMed.

Frequently Asked Questions

Hyperammonemia is a metabolic condition characterized by an excess of ammonia in the blood. If left untreated, high ammonia levels are toxic, especially to the brain, and can lead to severe neurological symptoms, coma, or death.

Sodium phenylacetate works by providing an alternative pathway for the removal of waste nitrogen. It conjugates with glutamine to form phenylacetylglutamine, a compound with two nitrogen atoms that is easily excreted by the kidneys.

No, sodium phenylacetate is most commonly administered as part of a combination product (Ammonul) with sodium benzoate. The two compounds work together to enhance the body's ability to remove excess waste nitrogen.

Sodium phenylacetate is administered intravenously via a central venous catheter in a controlled medical setting, such as a hospital. It is first given as an initial dose and followed by a continuous maintenance infusion.

Common side effects include vomiting, nausea, hyperglycemia (high blood sugar), and hypokalemia (low potassium). More serious side effects, such as neurotoxicity and metabolic acidosis, are also possible and require close monitoring.

Administering sodium phenylacetate through a central line is crucial because it can cause severe burns and tissue damage if it leaks from a peripheral (hand or arm) intravenous line.

No, sodium phenylacetate is not a cure for urea cycle disorders. It is an adjunctive therapy used to manage the acute hyperammonemic episodes associated with these genetic conditions by controlling dangerous ammonia levels.