1 What is Ammonul?

Brand: Ammonul

Generic: Sodium Phenylacetate And Benzoate

Ammonul is a combination medicine (Sodium Phenylacetate And Sodium Benzoate) which is a sterile, concentrated, aqueous solution. This combination drug is widely used to treat hyperammonemia in urea cycle disorders. The pH of the solution is between 6 and 8.

Sodium phenylacetate is a crystalline, white to off-white powder with a strong, offensive odor and it is soluble in water. On the contrary, sodium benzoate is a white and odorless, crystalline powder that is readily soluble in water.

Hyperammonemia is a metabolic condition, in which there is elevated ammonia in the blood and it causes increased entry of ammonia to the brain resulting in certain neurological disorders. 

Due to deficiency of enzymes of the urea cycle, accumulation of ammonia may also occur. This results in encephalopathy, coma, and death if remains undiagnosed and untreated. Ammonia is usually formed as a breakdown product of protein in the body. 

If the excessive ammonia cannot be removed by the body, serious unwanted effects may arise. This combined medicine works to reduce the higher amount of ammonia in the blood. 

Sodium phenylacetate and sodium benzoate combine with NH3 in the blood to form phenyl acetic glutamine or hippuric acid respectively. These are rapidly excreted in urine resulting in reduced blood ammonia.

This medicine should be given only by or under the direct supervision of a healthcare professional.

2 What To Know Before Using

If you are about to start Ammonul, the risk and benefit ratio of taking this drug should be considered. This is a decision that your doctor will make with your active participation. 

There are some important factors such as drug interaction, metabolic impairment, hypersensitivity reaction, pregnancy, lactation etc. which may alter the drug action.

Sometimes, presence of other health disorders affects the beneficial effects of this medicine and may even cause serious complications. Make sure you mention to your doctor if you have any other medical problems, especially congestive heart failure, edema, hyperglycemia, hypokalemia, seizures, liver and kidney diseases. 

The use of sodium phenylacetate and benzoate is contraindicated if there is history of hypersensitivity reactions to its components.

Certain drugs should not be used concurrently with such medications. It is always recommended to consult with your doctor if you are in need of some drugs for another health problem in order to avoid unwanted serious effects. 

You should know about the following drug interactions in order to get rid of unwanted complications: 

  • Some antibiotics such as penicillin may compete with phenylacetylglutamine and hippurate for active secretion by renal tubules, which may affect the overall disposition of the infused drug.
  • Probenecid is known to inhibit the renal transport of many organic compounds, including aminohippuric acid, and may affect renal excretion of phenylacetylglutamine and hippurate.
  • Valproic acid can induce hyperammonemia through inhibition of the synthesis of N-acetylglutamate, a co-factor for carbamyl phosphate synthetase. Therefore, administration of valproic acid to patients with urea cycle disorders may exacerbate their condition and antagonize the efficacy of this combination medicine.
  • Use of corticosteroids may cause a protein catabolic state and, thereby, potentially increase plasma ammonia levels in patients with impaired ability to form urea.

3 Proper Usage

Medicines should be used following the directions given by a doctor. The dose of Ammonul will vary according to patient’s condition or requirement. 

The amount of medicine that you take should not exceed the maximum therapeutic dose. Also, the frequency of your daily drug administration and the duration of drug therapy depend on the particular medical problem for which you are taking the medicine. 

Each ml of this combination drug contains 100 mg of sodium phenylacetate and 100 mg of sodium benzoate, and water. Sodium hydroxide and/or hydrochloric acid may have been used for pH adjustment.

This combination medicine is often indicated as adjunctive therapy to treat acute hyperammonemia and associated encephalopathy in patients with deficiency of enzymes of the urea cycle. 

This drug is given intravenously as a loading dose infusion administered over 90 to 120 minutes, followed by an equivalent maintenance dose infusion administered over 24 hours. 

The loading dose and the maintenance dose may vary depending on body weight and age of the patients as follows: 

For adults:

  • Loading dose (>20 kg): 5.5 g-5.5 g/m² IV infusion over 90-120 minutes.
  • Maintenance dose: 5.5 g-5.5 g/m² IV infusion over 24 hours.

For children:

  • Loading dose (<20 kg): 250 mg-250 mg/kg (2.5 mL/kg) IV infusion over 90-120 minutes.
  • Maintenance dose: 250 mg-250 mg/kg (2.5 mL/kg) IV infusion over 24 hours.

This drug must be diluted with sterile 10% dextrose injection before administration. The dilution and dosage are determined by weight for neonates, infants and young children, and by body surface area for larger patients, including older children, adolescents, and adults. 

Maintenance infusions may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications.

Such solutions are physically and chemically stable for up to 24 hours at room temperature and room lighting conditions. Other infusion solutions and drug products should not be administered together with this combination infusion solution. 

Such solutions may be prepared in glass and PVC containers. Such solutions should be inspected visually for particulate matter and discoloration before administration.

4 Precautions To Take

Before using Ammonul, there are some precautions you must take.The treatment should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. 

During and after infusion of such medications, ongoing monitoring of neurological status, plasma ammonia levels, clinical laboratory values, and clinical responses are crucial to assess patient response to treatment.

As this is a concentrated solution, it must be diluted before administration via a central line. Because sodium phenylacetate and sodium benzoate are metabolized in the liver and kidney, and since phenylacetylglutamine and hippurate are primarily excreted by the kidney, use caution when administering to patients with hepatic or renal insufficiency. 

This infusion has been associated with nausea and vomiting. An antiemetic may be administered during this infusion.

Moreover, you should discontinue oral antihyperammonemic drugs prior to administration. This combination drug should be used cautiously in hepatic or renal impairment, heart failure, and sodium retention associated with edema.

5 Potential Side Effects

There are some unwanted adverse effects associated with Ammonul along with its desired beneficial effects. These side-effects usually go away during the treatment episode as your body adjusts to the medicine. 

Your healthcare professional may advise you about the ways to prevent or reduce those unwanted side-effects. Sometimes, you may need to consult with the doctor if you feel any serious toxic effect. 

Nausea, vomiting, diarrhea, hyperglycemia, pyrexia, and certain skin disorders are the common adverse effects. In addition, some other adverse effects such as acidosis, agitation, anemia, respiratory distress, hypotension, convulsions, coma etc. may occur, but rarely.