Ammonul

Urea Cycle Disorder Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Sodium benzoate; sodium phenylacetate is administered as an intravenous infusion through a central line only. Peripheral infusion may cause burns.
Sodium benzoate; sodium phenylacetate is indicated for the adjunctive treatment of hyperammonemia. Caloric supplementation (ideally, > 80 cal/kg/day) and dietary protein restriction are needed concurrently. Non-protein calories should be given as glucose 8—10 mg/kg/day with Intralipid added. Also, all infants with hyperammonemic coma regardless of the cause need prompt hemodialysis. Further, concurrent hemodialysis may be advisable for moderate to severe hyperammonemic encephalopathy, for patients with a large ammonia burden, and for failure to respond within 4—8 hours of sodium benzoate; sodium phenylacetate initiation.
Continually assess the patient's neurological status, ammonia concentrations, and serum electrolyte concentrations until hyperammonemia has resolved, and the patient is able to tolerate oral therapy.
 
Reconstitution and dilution:
Ammonul is supplied as a 10% sodium benzoate; 10% sodium phenylacetate solution. Thus, each ml provides 100 mg of sodium benzoate and 100 mg of sodium phenylacetate.
Using the provided MilIex Durapore GV 33 mm sterile syringe filter (0.22 micrometer), withdraw the needed amount for the dosage and mix with at least 25 ml of 10% sterile dextrose injection per kilogram of the patient's weight. Dilution must be done in a glass or PVC container.
The presence of particulate matter may impact the safe use of sodium benzoate; sodium phenylacetate. Since particulate matter may not be readily seen on visual inspection, a filter must be employed in all cases regardless of whether particulate matter is seen in the vial.
Arginine HCl 10% injection can be mixed in the same vial. No other compatibility data are available.
Sodium benzoate; sodium phenylacetate does not contain preservatives. The solution is physically and chemically stable for 24 hours at room temperature and lighting conditions once it has been reconstituted. Discard any unused product; do no store for reuse.
 
Intravenous infusion:
Do not administer undiluted product.
Visually inspect parenterally products for discoloration and particulate matter prior to administration whenever solution and container permit.
If visibly opaque particles, discoloration, or other foreign particles are observed, the solution should not be used.
Sodium benzoate; sodium phenylacetate should be infused through a different line than the one used for the infusion of other solutions or medications. If use of a separate line is not possible, the line should be flushed with at least 15 ml of saline solution before and after infusion with sodium benzoate; sodium phenylacetate.
The loading dose should be infused over 90 minutes. Only one loading dose should be given (see Dosage). The maintenance dose should be infused over 24 hours immediately following the loading dose. Closely monitor the infusion site for possible drug extravasation (see Contraindications).

seizures / Delayed / 6.0-6.0
cerebral edema / Early / 5.0-5.0
hyperkalemia / Delayed / 0-3.0
coma / Early / 3.0-3.0
pneumothorax / Early / 0-3.0
acute respiratory distress syndrome (ARDS) / Early / 0-3.0
pulmonary edema / Early / 0-3.0
visual impairment / Early / 0-3.0
disseminated intravascular coagulation (DIC) / Delayed / 3.0-3.0
thrombosis / Delayed / 0-3.0
GI bleeding / Delayed / 0-3.0
coagulopathy / Delayed / 0-3.0
hepatic failure / Delayed / 0-3.0
pancytopenia / Delayed / 0-3.0
renal failure (unspecified) / Delayed / 0-3.0
anuria / Delayed / 0-3.0
increased intracranial pressure / Early / 0-3.0
cerebral degeneration / Delayed / 0-3.0
intracranial bleeding / Delayed / 0-3.0
cardiac arrest / Early / 0-3.0
bradycardia / Rapid / 0-3.0
cardiomyopathy / Delayed / 0-3.0
pericardial effusion / Delayed / 0-3.0
skin necrosis / Early / Incidence not known

hypokalemia / Delayed / 7.0-7.0
hyperglycemia / Delayed / 7.0-7.0
impaired cognition / Early / 6.0-6.0
hyperammonemia / Delayed / 5.0-5.0
metabolic acidosis / Delayed / 4.0-4.0
hypotension / Rapid / 4.0-4.0
anemia / Delayed / 4.0-4.0
encephalopathy / Delayed / 0-3.0
hallucinations / Early / 0-3.0
confusion / Early / 0-3.0
psychosis / Early / 0-3.0
hypocalcemia / Delayed / 3.0-3.0
dehydration / Delayed / 0-3.0
fluid retention / Delayed / 0-3.0
tetany / Early / 0-3.0
hypertension / Early / 0-3.0
edema / Delayed / 0-3.0
hypernatremia / Delayed / 0-3.0
tachypnea / Early / 0-3.0
dyspnea / Early / 0-3.0
hypoglycemia / Early / 0-3.0
cholestasis / Delayed / 0-3.0
jaundice / Delayed / 0-3.0
thrombocytopenia / Delayed / 0-3.0
bleeding / Early / 0-3.0
urinary retention / Early / 0-3.0
subdural hematoma / Early / 0-3.0
ataxia / Delayed / 0-3.0
chest pain (unspecified) / Early / 0-3.0

vomiting / Early / 9.0-9.0
fever / Early / 5.0-5.0
irritability / Delayed / 3.0-3.0
agitation / Early / 3.0-3.0
hyperventilation / Early / 0-3.0
alopecia / Delayed / 0-3.0
rash / Early / 0-3.0
urticaria / Rapid / 0-3.0
flushing / Rapid / 0-3.0
injection site reaction / Rapid / 3.0-3.0
pruritus / Rapid / 0-3.0
nausea / Early / 3.0-3.0
asthenia / Delayed / 0-3.0
infection / Delayed / 3.0-3.0
hyporeflexia / Delayed / 0-3.0
tremor / Early / 0-3.0
diarrhea / Early / 3.0

Ammonul

Rx

Adjunctive IV treatment of acute hyperammonemia associated with urea cycle disorders; forms nitrogenous compounds through conjugation with amino acids; helps remove ammonia from the blood and prevent ammonia reaccumulation.

55 mL/m2 (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) IV loading dose through a central line over 90 to 120 minutes, then give a maintenance dose of 55 mL/m2 (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) IV through a central line over 24 hours. Administer each dose with 2 mL/kg (provides 200 mg/kg) arginine HCl IV. Maintenance infusions may be given daily, each over 24 hours, until plasma ammonia concentrations normalize or until the patient can tolerate oral nutrition and medications.

2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) IV loading dose through a central line over 90 to 120 minutes, then give a maintenance dose of 2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) IV through a central line over 24 hours. Administer each dose with 2 mL/kg (provides 200 mg/kg) arginine HCl IV. Maintenance infusions may be given daily, each over 24 hours, until plasma ammonia concentrations normalize or until the patient can tolerate oral nutrition and medications.

55 mL/m2 (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) IV loading dose through a central line over 90 to 120 minutes, then give a maintenance dose of 55 mL/m2 (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) IV through a central line over 24 hours. Administer each dose with 6 mL/kg (provides 600 mg/kg) arginine HCl IV. Maintenance infusions may be given daily, each over 24 hours, until plasma ammonia concentrations normalize or until the patient can tolerate oral nutrition and medications.

2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) IV loading dose through a central line over 90 to 120 minutes, then give a maintenance dose of 2.5 mL/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) IV through a central line over 24 hours. Administer each dose with 6 mL/kg (provides 600 mg/kg) arginine HCl IV. Maintenance infusions may be given daily, each over 24 hours, until plasma ammonia concentrations normalize or until the patient can tolerate oral nutrition and medications.

Specific guidelines for dosage adjustments in hepatic impairment are not available; however, care should be taken in patients with hepatic impairment, as the liver is one of the primary sites of conjugation of phenylacetylglutamine and hippuric acid.

Specific guidelines for dosage adjustments in renal impairment are not available; close monitoring for renal clearance of drug metabolites and ammonia is necessary for clinical assessment.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Albuterol; Budesonide: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Aluminum Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Amoxicillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Amoxicillin; Clavulanic Acid: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Ampicillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Ampicillin; Sulbactam: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Antacids: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aspirin, ASA: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Dipyridamole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Omeprazole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Oxycodone: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Azelastine; Fluticasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Beclomethasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Betamethasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Bismuth Subsalicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Budesonide: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Budesonide; Formoterol: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Choline Salicylate; Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Ciclesonide: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment.
Corticosteroids: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Cortisone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Deflazacort: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Dexamethasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Dichlorphenamide: (Moderate) Use dichlorphenamide and sodium benzoate; sodium phenylacetate together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dicloxacillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Fludrocortisone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Flunisolide: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Fluticasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Fluticasone; Salmeterol: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Fluticasone; Vilanterol: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Formoterol; Mometasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Hydrocortisone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Methadone: (Minor) As methadone is a weak base, the renal elimination of methadone is increased by urine acidification. Thus acidifying agents may lower the serum methadone concentration. The limited amounts of circulating methadone that undergo glomerular filtration are partially reabsorbed by the kidney tubules, and this reabsorption is pH-dependent. Several studies have demonstrated that methadone is cleared faster from the body with an acidic urinary pH as compared with a more basic pH.
Methylprednisolone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Mometasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Nafcillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Olopatadine; Mometasone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Oxacillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillin G Benzathine: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillin G Procaine: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillin G: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillin V: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Penicillins: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Piperacillin; Tazobactam: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Prednisolone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Prednisone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Probenecid: (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Probenecid; Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment. (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Salsalate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Triamcinolone: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Valproic Acid, Divalproex Sodium: (Major) Valproic acid may inhibit N-acetylglutamate synthase, which is the essential cofactor for carbamyl phosphate synthetase in the urea cycle. The clinician should pay careful attention to patients with urea cycle deficiencies who are receiving valproic acid because their plasma ammonia concentrations could rise significantly. Discontinuation of valproate therapy may be necessary.
Vonoprazan; Amoxicillin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.

Ammonul/Sodium Phenylacetate, Sodium Benzoate Intravenous Inj Sol: 10-10%

55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) and maintenance dose of 55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) and maintenance dose of 55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) and maintenance dose of 55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

> 20 kg: 55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate) and maintenance dose of 55 ml/m2 IV as a loading dose (provides 5.5 g/m2 of sodium phenylacetate and 5.5 g/m2 of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.
< 20 kg: 2.5 ml/kg IV as a loading dose (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) and a maintenance dose of 2.5 ml/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

2.5 ml/kg IV as a loading dose (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) and a maintenance dose of 2.5 ml/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

2.5 ml/kg IV as a loading dose (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate) and a maintenance dose of 2.5 ml/kg (provides 250 mg/kg of sodium phenylacetate and 250 mg/kg of sodium benzoate), both administered on day 1. Subsequent days, only the maintenance dose is given; do not give more than 1 loading dose.

Mechanism of Action: Sodium benzoate; sodium phenylacetate help to reduce serum ammonia and glutamine concentrations. Patients with high ammonia and glutamine concentrations are at particular risk for encephalopathies and neurotoxicity. The urea cycle is normally responsible for maintaining low blood concentrations of ammonia and glutamine from protein breakdown. The normal urea cycle requires numerous enzyme-catalyzed steps to form nitrogenous waste such as urea. Hyperammonemia may occur when there is a deficiency in one or more urea cycle enzymes or a cofactor: N-acetylglutamate synthetase, carbamyl phosphate synthetase, argininosuccinate synthetase, ornithine transcarbamylase, or argininosuccinate lyase. Arginine becomes an essential amino acid when carbamyl phosphate synthetase, argininosuccinate synthetase, ornithine transcarbamylase, or argininosuccinate lyase is deficient (see Dosage). If essential amino acids are not available, protein catabolism occurs, which increases ammonia concentrations.Ammonia in the blood may be converted to glycine, glutamine, or carbamyl phosphate. In contrast to the normal urea cycle, only two steps are required to form nitrogenous molecules from sodium benzoate; sodium phenylacetate. Phenylacetate conjugates glutamine in the liver and kidneys to form glutamine phenylacetate, which is acetylated to form phenylacetylglutamine. Benzoate undergoes acylation and conjugates with glycine to form hippuric acid. These two nitrogenous waste products, phenylacetylglutamine and hippuric acid, are excreted by the kidneys through glomerular filtration and tubular secretion. The scavenged glutamine and glycine are regenerated, which reduces the serum ammonia concentration and reduces the nitrogen load once conversion to phenylacetylglutamine and hippuric acid occurs, and the products are excreted from the body. Thus, ammonia is eliminated indirectly from the blood. Similar to urea, two moles of nitrogen are removed per mole of phenylacetylglutamine. One mole of nitrogen is removed per mole of hippuric acid.

Sodium benzoate; sodium phenylacetate is administered by intravenous infusion through a central line only. Both benzoate and phenylacetate display nonlinear kinetics. Total clearance decreases and systemic exposure increases with increasing doses. As compared with benzoate, phenylacetate is cleared at a much slower rate. Phenylacetate conjugates glutamine in the liver and kidneys to form glutamine phenylacetate, which is acetylated to form phenylacetylglutamine. Benzoate undergoes acylation and conjugates with glycine to form hippuric acid. Hippuric acid formation from benzoate occurs faster than phenylacetylglutamine formation from phenylacetate. Both phenylacetylglutamine and hippuric acid undergo glomerular filtration and tubular secretion.
 
Most patients with hyperammonemia have sustained reductions in their mean ammonia concentration within 4 hours of sodium benzoate; sodium phenylacetate administration. Some patients may have an increase in plasma ammonia concentrations after sodium benzoate; sodium phenylacetate administration (see Adverse Reactions).

Following a 24-hour infusion of sodium benzoate; sodium phenylacetate, phenylacetate was detectable in plasma 24 hours after the end of the infusion with a Tmax of 2 hours; while benzoate was undetectable 14 hours after the infusion cessation with a Tmax of 1.5 hours.

Available data with sodium benzoate; sodium phenylacetate use in human pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with sodium benzoate; sodium phenylacetate.

There are no data on the presence of sodium phenylacetate, sodium benzoate in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for sodium benzoate; sodium phenylacetate and any potential adverse effects on the breastfed infant from sodium benzoate; sodium phenylacetate or from the underlying maternal condition.