Ammonul (Sodium phenylacetate/Sodium benzoate) provides an alternative pathway for the removal of ammonia and nitrogen from the body.

Ammonul (Sodium phenylacetate/Sodium benzoate) Indications

• Hyperammonemia:

  • It is indicated for the treatment of acute hyperammonemia and associated encephalopathy in patients with urea cycle enzyme deficiencies

Ammonul (Sodium phenylacetate/Sodium benzoate) Dose in Adults

Note:

• Therapy should be started immediately in case of hyperammonemia with a loading dose over 90 to 120 minutes, followed by an equivalent maintenance infusion given over 24 hours.
• Dosage is based on weight for children and body surface area for adults. Repeated doses should not be given due to the risk of phenylacetate neurotoxicity.
• Therapy is continued until normal ammonia levels are achieved or the patient can tolerate orally. Antiemetics should be given to control of infusion-associated nausea/vomiting.

Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders:

• 55 mL/m² (provides sodium phenylacetate 5.5 g/m2 and sodium benzoate 5.5 g/m2) intravenous along with arginine.
• Hemodialysis in patients with severe hyperammonemia or refractory to sodium phenylacetate/sodium benzoate is advised

Ammonul (Sodium phenylacetate/sodium benzoate) dose in children:

Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders [UCD]):

Note: Administer with arginine; arginine dose varies based on type of UCD.

• Infants and Children ≤20 kg:

  • Loading dose: 5 mL/kg (provides sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg) intravenous
  • maintenance infusion of 2.5 mL/kg/24 hours (provides sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg per 24 hours)

• Children and Adolescents >20 kg:

  • Loading dose: 55 mL/m2 (provides sodium phenylacetate 5.5 g/m2 and sodium benzoate 5.5 g/m2) intravenous
  • maintenance infusion of 55 mL/m2/24 hours (provides sodium phenylacetate 5.5 g/m² and sodium benzoate 5.5 g/m2 per 24 hours)

Pregnancy Risk Factor C

• Animal reproduction studies have not been elucidated.

Sodium phenylacetate and sodium benzoate use during breastfeeding:

• Sodium phenylacetate/sodium benzoate secretion in breast milk is not known
• The manufacturer recommends that caution be exercised when administering sodium phenylacetate/sodium benzoate to nursing women.

Ammonul Dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer’s labeling; however, the drug metabolites and ammonia are excreted by the kidneys,therefore close monitoring is required.

Ammonul Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.

Common Side Effects of Ammonul (Sodium phenylacetate and sodium benzoate):

• Infection:

  • Infection

Rare Side Effects of Ammonul (Sodium phenylacetate and sodium benzoate):

• Cardiovascular:

  • Hypotension
  • Bradycardia
  • Cardiac Failure
  • Cardiogenic Shock
  • Cardiomyopathy
  • Chest Pain
  • Edema
  • Flushing
  • Hepatic Artery Stenosis
  • Hypertension
  • Low Cardiac Output
  • Myocardial Rupture
  • Pericardial Effusion
  • Septic Shock
  • Subdural Hematoma
  • Thrombosis
  • Venous Thrombosis

• Central Nervous System:

  • Decreased Mental Acuity
  • Seizure
  • Cerebral Edema
  • Agitation
  • Coma
  • Absent Reflexes
  • Acute Psychosis
  • Aggressive Behavior
  • Ataxia
  • Brain Disease
  • Cerebral Atrophy
  • Cerebral Hemorrhage
  • Cerebral Herniation
  • Cerebral Infarction
  • Clonus
  • Confusion
  • Hallucination
  • Impaired Consciousness
  • Increased Intracranial Pressure
  • Paralysis

• Dermatologic:

  • Alopecia
  • Maculopapular Rash
  • Pruritus
  • Skin Rash
  • Urticaria

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hypokalemia
  • Hyperammonemia
  • Metabolic Acidosis
  • Acidosis
  • Hypocalcemia
  • Alkalosis
  • Dehydration
  • Fluid Retention
  • Hyperkalemia
  • Hypernatremia
  • Hypervolemia
  • Respiratory Acidosis

• Gastrointestinal:

  • Vomiting
  • Diarrhea
  • Nausea
  • Abdominal Distention
  • Cholestasis
  • Gastrointestinal Hemorrhage

• Genitourinary:

  • Urinary Tract Infection
  • Anuria
  • Urinary Retention

• Hematologic & Oncologic:

  • Anemia
  • Disseminated Intravascular Coagulation
  • Altered Serum Glucose
  • Blood Coagulation Disorder
  • Hemangioma
  • Hemorrhage
  • Increased Serum Ph
  • Pancytopenia
  • Pulmonary Hemorrhage
  • Thrombocytopenia

• Hepatic:

  • Hepatic Failure
  • Hepatotoxicity
  • Jaundice

• Infection:

  • Sepsis

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Tetany
  • Tremor
  • Weakness

• Ophthalmic:

  • Blindness

• Renal:

  • Renal Failure

• Respiratory:

  • Respiratory Distress
  • Acute Respiratory Distress
  • Aspiration Pneumonia
  • Dyspnea
  • Hypercapnia
  • Hyperventilation
  • Kussmaul’s Respiration
  • Pneumothorax
  • Pulmonary Edema
  • Respiratory Alkalosis
  • Respiratory Insufficiency
  • Tachypnea

• Miscellaneous:

  • Fever
  • Multi-Organ Failure

Contraindication to Ammonul (Sodium phenylacetate and sodium benzoate):

There are no contraindications listed in the manufacturer’s labeling.

Warnings and Precautions

• Acute hyperammonemia:

  • Ammonia level should be immediately decreased by protein restriction, caloric supplementation, and hemodialysis otherwise brain death will occur.
  • Nonprotein calories such as glucose with IV fat emulsion should be given. Caloric intake should be >80 cal/kg/day.

• Extravasation:

  • It is an irritant with vesicant-like properties.
  • The infusion should be stopped and resume at a different infusion site if necessary in case of extravasation.

• Fluid overload:

  • People with heart failure, severe renal impairment or sodium retention edema, should be used with caution.

• Gastrointestinal effects:

  • It can cause nausea/vomiting therefore antiemetics are necessary.

• Hypokalemia:

  • Close monitoring is required.

• Metabolic acidosis/ hyperventilation:

  • Use may cause hyperventilation and metabolic acidosis mimicking salicylate overdose.

• Neurotoxicity:

  • Phenylacetate may result in reversible neurotoxicity presenting as fatigue, lightheadedness, somnolence.

Sodium phenylacetate and sodium benzoate: Drug Interaction

Monitoring parameters:

Monitoring is required for

• infusion site
• clinical response
• LFTs
• Serum electrolytes
• Plasma ammonia,glutamine,
• Blood glucose level
• GCS
• Tacypnoea
• CT /MRI scan or fundoscopic evidence of cerebral edema, and/or of gray matter and white matter

How to administer Ammonul (Sodium phenylacetate and sodium benzoate)?

• Dilution is a must before infusion. Infuse via central line ONLY (administration via peripheral line may cause burning).
• The loading dose is given over 90 to 120 minutes and maintenance dose over 24 hours.
• Maybe an irritant with vesicant-like properties, proper positioning of the catheter is important before and during infusion.
• Stop infusion and start at a different infusion site if extravasation occurs.

Mechanism of action of Ammonul (Sodium phenylacetate and sodium benzoate):

• Sodium phenylacetate and sodium benzoate cause metabolite formation providing alternate pathways for the removal of ammonia.
• One mole of sodium phenylacetate removes two moles of nitrogen; one mole of sodium benzoate removes one mole of nitrogen.

Metabolism: Occurs in liver and kidneys sodium phenylacetate conjugates with glutamine, forming the active metabolite, phenylacetylglutamine (PAG) sodium benzoate combines with glycine to form the active metabolite hippuric acid (HIP)

Excretion: Primarily urine

Sodium phenylacetate and sodium benzoate Brand Names (International):

• Ammonul

Sodium phenylacetate and sodium benzoate Brand Names in Pakistan:

No Brands Available in Pakistan.