What medication is given to reduce ammonia levels? A guide to treatment options for hyperammonemia

October 11, 2025 •

4 min read

High ammonia levels in the blood, a condition known as hyperammonemia, can be toxic to the brain and is often linked to severe liver disease or genetic urea cycle disorders. To combat this, several prescription medication options are available, with the specific choice depending on the underlying cause and severity of the condition.

Quick Summary

Different medications are used to reduce high ammonia levels, including first-line options like lactulose and rifaximin for liver disease and specialized ammonia scavengers for genetic disorders. The treatment approach depends on the underlying cause, severity, and patient-specific factors.

Key Points

Lactulose: A synthetic sugar and first-line treatment for hepatic encephalopathy (HE), works by acidifying the colon and flushing out ammonia through increased bowel movements.
Rifaximin: A non-absorbable antibiotic that reduces ammonia-producing gut bacteria, often used with lactulose to prevent recurrent HE episodes.
Ammonia Scavengers: Specialized intravenous or oral medications (e.g., sodium phenylacetate, sodium benzoate, phenylbutyrate) used for genetic urea cycle disorders (UCDs) to provide an alternative nitrogen excretion pathway.
Emergency Treatment: In severe, acute cases of hyperammonemia, hemodialysis is used to rapidly remove excess ammonia from the blood, especially in critically ill newborns.
Underlying Cause: The specific medication depends on whether the hyperammonemia is caused by liver disease (HE) or a genetic urea cycle disorder (UCD).
Medical Supervision: All medications for high ammonia levels require a doctor's prescription and must be managed under close medical supervision due to the risks of hyperammonemia.

Understanding Hyperammonemia and its Dangers

Ammonia is a toxic waste product created during protein digestion and metabolism. The liver, through a process called the urea cycle, normally converts this ammonia into urea, which is then excreted by the kidneys. When the liver is damaged, or if there is a genetic defect in the urea cycle, ammonia can accumulate in the bloodstream, leading to hyperammonemia.

Symptoms of high ammonia can range from mild confusion and fatigue to severe neurological issues such as seizures, coma, and even death. The neurological symptoms associated with liver disease are collectively known as hepatic encephalopathy (HE). Given these serious risks, managing ammonia levels is a critical component of treatment for conditions like HE and urea cycle disorders (UCDs).

Medications for Managing High Ammonia Levels

Lactulose

Lactulose is a synthetic sugar and a first-line treatment for managing hyperammonemia, particularly in cases of hepatic encephalopathy. It works in two primary ways to reduce ammonia levels:

Acidification of the colon: When lactulose reaches the colon, gut bacteria metabolize it into organic acids, which lowers the pH level. This acidic environment converts ammonia (NH3) into ammonium (NH4+), an ionized form that cannot be easily absorbed back into the bloodstream.
Laxative effect: Lactulose is also an osmotic laxative, drawing water into the colon and increasing bowel movements. This helps to flush toxins, including trapped ammonium, out of the body more quickly.

Typically administered as an oral solution, lactulose is dosed to produce 2 to 3 soft bowel movements per day. For severe cases, it can also be given as an enema. While highly effective, common side effects include gas, bloating, and diarrhea.

Rifaximin

Rifaximin (brand name Xifaxan) is a non-absorbable antibiotic used to treat and prevent episodes of hepatic encephalopathy. Because it is minimally absorbed into the bloodstream, it acts locally in the gut to reduce the number of ammonia-producing bacteria.

Mechanism of action: Rifaximin works by inhibiting bacterial RNA synthesis, which reduces the population of urease-producing bacteria in the gut that convert urea into ammonia.
Combination therapy: It is often used in combination with lactulose, offering a synergistic effect that further reduces ammonia levels and lowers the risk of recurrent HE.
Long-term use: For patients with a history of recurrent HE, rifaximin is often continued long-term as a maintenance therapy to prevent future episodes.

Ammonia Scavengers

For genetic urea cycle disorders (UCDs), where the body's natural ammonia detoxification pathway is impaired, specialized ammonia-scavenger medications are used. These drugs provide alternative routes for the body to excrete nitrogen waste.

Sodium Phenylacetate and Sodium Benzoate (Ammonul): This combination is administered intravenously in a hospital setting for the treatment of acute, dangerously high ammonia levels, such as during a hyperammonemic crisis. The components conjugate with amino acids, creating products that are then excreted by the kidneys.
Sodium Phenylbutyrate (Buphenyl, Pheburane): An oral medication used for the long-term management of UCDs. It works similarly to the intravenous formulation by promoting the excretion of nitrogen waste. A newer formulation, glycerol phenylbutyrate (Ravicti), offers a more tolerable taste and odor.

Other Supportive Medications

Beyond these core treatments, other medications and supplements may play a role in managing hyperammonemia:

L-ornithine L-aspartate (LOLA): This compound is given to stimulate the body's natural urea cycle, particularly in cases of liver cirrhosis where the cycle is sluggish.
Carglumic Acid (Carbaglu): A specific treatment for N-acetylglutamate synthase (NAGS) deficiency, a rare genetic UCD, that activates the enzyme crucial for the urea cycle.
Antibiotics (historical): Older antibiotics like neomycin and metronidazole have been used in the past, but their use has declined due to significant side effects and the emergence of safer alternatives like rifaximin.

Comparison of Key Hyperammonemia Medications


Feature	Lactulose	Rifaximin	Sodium Phenylacetate/Benzoate	Sodium Phenylbutyrate	L-ornithine L-aspartate (LOLA)
Mechanism	Colon acidification and osmotic laxative effect	Reduces gut ammonia-producing bacteria	Provides alternative pathway for nitrogen excretion	Provides alternative pathway for nitrogen excretion	Fuels the urea cycle in the liver
Primary Indication	Hepatic encephalopathy due to liver disease	Recurrent hepatic encephalopathy	Acute hyperammonemia from urea cycle disorders	Chronic hyperammonemia from urea cycle disorders	Elevated ammonia in liver conditions
Administration	Oral solution or enema	Oral tablets	Intravenous (IV) infusion	Oral tablets, powder, or pellets	Oral or IV
Combination Therapy	Often used with rifaximin for HE	Often used with lactulose for HE	Used together in one formulation (Ammonul)	Part of a broader treatment plan for UCDs	May be used with standard HE therapy
Adverse Effects	Diarrhea, gas, nausea	Nausea, bloating, headache	Electrolyte imbalances, nausea, seizures	Nausea, vomiting, salty taste	Diarrhea, abdominal cramps

The Role of Dialysis

In cases of severe, acute hyperammonemia that do not respond rapidly to medication, particularly in neonates or patients with very high ammonia levels (above 500 µg/dL), hemodialysis is the most effective and rapid method for removing ammonia from the blood. Hemodialysis is a life-saving intervention used in a hospital setting until the ammonia level can be controlled by medication and other supportive measures.

Conclusion

Deciding what medication is given to reduce ammonia levels depends on the underlying cause of the condition. For hepatic encephalopathy stemming from liver disease, lactulose is the traditional first-line treatment, often used in conjunction with rifaximin to enhance effectiveness and prevent recurrence. For rare, genetic urea cycle disorders, specialized ammonia-scavenger medications like sodium phenylbutyrate or intravenous sodium phenylacetate and sodium benzoate are the standard of care. Due to the severe neurological risks associated with hyperammonemia, all treatment decisions should be made and closely monitored by a healthcare professional.

For more detailed information on hepatic encephalopathy and its management, consult the American Liver Foundation.(https://liverfoundation.org/liver-diseases/complications-of-liver-disease/hepatic-encephalopathy/treating-hepatic-encephalopathy/)

Frequently Asked Questions

The primary treatment for hepatic encephalopathy is lactulose, a synthetic sugar that acidifies the colon to prevent ammonia absorption and promotes its excretion through increased bowel movements.

Rifaximin is an antibiotic that stays in the gastrointestinal tract and reduces the number of ammonia-producing bacteria. By targeting these bacteria, it helps lower the overall amount of ammonia produced in the gut.

Ammonia scavengers like sodium phenylbutyrate and sodium benzoate are typically used for rare, genetic urea cycle disorders. Treatments for liver disease-related hyperammonemia primarily focus on lactulose and rifaximin.

Intravenous medication, such as the combination of sodium phenylacetate and sodium benzoate, is used for severe, acute hyperammonemic episodes in a hospital setting. Oral medications like lactulose and rifaximin are used for less severe or long-term management.

Yes, lactulose and rifaximin are often used together, especially for patients with a history of recurrent hepatic encephalopathy. The combination offers a more effective strategy for managing ammonia levels.

For hyperammonemia, medical treatment is almost always necessary. While a low-protein diet can help reduce the amount of ammonia produced, it is not sufficient on its own for managing conditions like hepatic encephalopathy or urea cycle disorders.

During a hyperammonemic crisis, ammonia levels rise to dangerously high levels, causing severe neurological symptoms. Emergency treatment is required and may include medication, hemodialysis, and supportive care in a hospital setting.