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:
- When treating hyperammonemia, start with a loading dose given slowly over 90 to 120 minutes, then switch to a continuous maintenance infusion over 24 hours.
- Begin treatment as soon as hyperammonemia is diagnosed, especially in neonates with coma, and continue until ammonia levels normalize or the patient can eat and take medications by mouth.
- The dosage depends on weight for young children and body size for older patients.
- Avoid repeating loading doses to prevent potential neurotoxic effects from prolonged high plasma levels of the medication.
- Antiemetics may be given during the infusion to help manage nausea and vomiting.
Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders:
- In the treatment of acute hyperammonemia due to urea cycle disorders, the recommended IV dose of sodium phenylacetate and sodium benzoate is 55 mL/m^2, which provides 5.5 grams/m^2 of each medication.
- This dosage should be co-administered with arginine.
- In cases of severe hyperammonemia or when the patient does not respond well to sodium phenylacetate/sodium benzoate therapy alone, hemodialysis may be considered as an adjunctive treatment.
Ammonul (Sodium phenylacetate/sodium benzoate) dose in children:
Note:
- Administer the sodium phenylacetate and sodium benzoate as a loading dose over 90 to 120 minutes, followed by an equivalent maintenance infusion over 24 hours.
- The dosage should be adjusted based on weight for infants and young children and body surface area for older children and adolescents.
- Start treatment immediately upon diagnosing hyperammonemia, and continue until ammonia levels normalize or the patient can take oral nutrition and medications.
- Antiemetics can be given during the infusion to manage nausea and vomiting.
Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders [UCD]):
In the treatment of acute hyperammonemia due to urea cycle disorders (UCD) with Ammonul (sodium phenylacetate and sodium benzoate), the dosage varies based on the weight of the patient.
- For infants and children weighing ≤20 kg, the recommended dosage is a loading dose of 2.5 mL/kg, which provides sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg, followed by a maintenance infusion of 2.5 mL/kg/24 hours, providing the same amounts of both medications per 24 hours.
- For children and adolescents weighing >20 kg, the loading dose is 55 mL/m^2, which provides sodium phenylacetate 5.5 g/m^2 and sodium benzoate 5.5 g/m^2, followed by a maintenance infusion of 55 mL/m^2/24 hours, providing the same amounts of both medications per 24 hours.
It's important to administer sodium phenylacetate and sodium benzoate concomitantly with arginine, with the arginine dose varying based on the type of UCD.
Pregnancy Risk Factor C
- The pregnancy risk factor C indicates that there haven't been adequate studies conducted on pregnant women, and animal reproduction studies with this combination of medications (sodium phenylacetate and sodium benzoate) haven't been carried out either.
- This classification suggests caution should be exercised when considering the use of these medications during pregnancy, and the potential benefits should be weighed against the potential risks.
Sodium phenylacetate and sodium benzoate use during breastfeeding:
- Since it's uncertain whether sodium phenylacetate and sodium benzoate are excreted in breast milk, caution is advised when administering these medications to nursing women.
- The manufacturer recommends exercising caution in such cases.
Ammonul Dose adjustment in renal disease:
- Although the manufacturer's labeling doesn't specify dosage adjustments, it's important to note that the drug metabolites and ammonia are excreted by the kidneys.
- Therefore, caution should be exercised when using sodium phenylacetate and sodium benzoate, especially in patients with impaired kidney function.
- Close monitoring is recommended to ensure proper excretion and to prevent potential adverse effects.
- Adjustments to the dosage may be necessary based on individual patient factors and renal function.
Ammonul Dose adjustment in liver disease:
- Since there are no dosage adjustments provided in the manufacturer's labeling for hepatic impairment, caution should be exercised when administering sodium phenylacetate and sodium benzoate to patients with liver dysfunction.
- Hepatic impairment can affect the metabolism and clearance of medications, potentially leading to increased drug levels and adverse effects.
- Close monitoring of liver function and clinical response is advised, and dosage adjustments may be necessary based on individual patient factors.
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):
- The absence of contraindications listed in the manufacturer's labeling indicates that there are no specific situations in which the use of sodium phenylacetate and sodium benzoate is strictly prohibited.
Warnings and Precautions
Acute hyperammonemia:
- Uncontrolled hyperammonemia can lead to severe consequences, including brain death.
- It's crucial to promptly employ all available therapies to lower ammonia levels, such as hemodialysis, caloric supplementation, and restricting dietary protein intake.
- Nonprotein calories, primarily in the form of glucose (8 to 10 mg/kg/minute), should be administered, supplemented with IV fat emulsion.
- Efforts should be made to ensure a daily caloric intake of over 80 calories per kilogram to support metabolic needs and aid in recovery.
Extravasation:
- When administering sodium phenylacetate and sodium benzoate, it's crucial to use a central line for infusion to prevent extravasation, as peripheral administration may cause burning due to its irritant properties.
- While it doesn't possess typical vesicant properties, it can still cause tissue irritation.
- If extravasation is suspected, discontinue the infusion immediately and consider resuming at a different infusion site, if necessary, to minimize the risk of local tissue damage.
Fluid overload:
- Due to its significant sodium content, sodium phenylacetate and sodium benzoate should be used cautiously, if at all, in patients who are at risk for fluid overload, such as those with heart failure or severe renal impairment, as well as those prone to sodium retention edema.
- If there are signs of clinically significant fluid overload, discontinuing the use of these medications is recommended.
- Close monitoring of fluid balance and clinical status is essential when administering sodium phenylacetate and sodium benzoate to patients with these risk factors.
Gastrointestinal effects:
- Nausea and vomiting are potential gastrointestinal side effects of sodium phenylacetate and sodium benzoate therapy.
- To mitigate these effects, premedication with antiemetics may be administered prior to infusion.
- This can help manage nausea and vomiting and improve patient tolerance to the treatment.
- Close monitoring for gastrointestinal symptoms is recommended during and after infusion, and appropriate supportive measures should be taken as needed.
Hypokalemia:
- Hypokalemia, a condition characterized by low potassium levels in the blood, is a potential side effect of sodium phenylacetate and sodium benzoate therapy.
- It's important to monitor plasma potassium levels closely during treatment and to initiate appropriate treatment if hypokalemia occurs.
Metabolic acidosis/ hyperventilation:
- The use of sodium phenylacetate and sodium benzoate may lead to hyperventilation and metabolic acidosis.
- These medications contain compounds that are structurally similar to salicylate.
- Consequently, adverse effects commonly associated with salicylate overdose, such as hyperventilation and metabolic acidosis, may occur with their use.
- It's crucial to monitor patients closely for signs of these complications during treatment and to take appropriate measures to manage them as needed.
Neurotoxicity:
- Neurotoxicity is a potential side effect of phenylacetate, manifesting as symptoms like fatigue, lightheadedness, and somnolence.
- These symptoms may occur at the beginning of treatment and typically resolve upon discontinuation of the medication.
- It's important to monitor patients closely for any signs of neurotoxicity during sodium phenylacetate and sodium benzoate therapy, and if such symptoms occur, discontinuing the treatment may be necessary to prevent further adverse effects.
Hepatic impairment:
- Given the potential impairment of the metabolism of sodium phenylacetate and sodium benzoate in patients with hepatic impairment, caution is advised when using these medications in such individuals.
- Monitoring liver function and clinical response closely is important in these cases.
- Adjustments to the dosage may be necessary based on individual patient factors and hepatic function.
Renal impairment:
- In patients with renal impairment, sodium phenylacetate and sodium benzoate should be used cautiously due to the potential reduction in the excretion of drug metabolites, such as phenylacetylglutamine and hippurate, as well as ammonia, which are primarily eliminated by the kidneys.
- Additionally, the use of these medications may predispose patients to fluid overload, further complicating renal function.
- Close monitoring of renal function and fluid status is essential, and adjustments to the dosage may be necessary based on individual patient factors and renal function.
Sodium phenylacetate and sodium benzoate: Drug Interaction
|
Probenecid |
May increase the serum concentration of Sodium Phenylacetate. Specifically, probenecid may inhibit the renal transport of the phenylacetylglutamine metabolite of sodium phenylacetate. |
|
Probenecid |
May increase the serum concentration of Sodium Benzoate. Specifically, probenecid may inhibit the renal transport of the hippuric acid metabolite of sodium benzoate. |
Monitoring parameters:
Monitoring Parameters for Hyperammonemia
- Neurologic Status: Watch for changes in alertness, behavior, or consciousness.
- Glasgow Coma Scale: Assess the level of consciousness regularly.
- Tachypnea: Monitor breathing rate for signs of respiratory distress.
- Imaging: Consider CT or MRI scans or fundoscopic examination for signs of cerebral edema or brain damage.
- Biochemical Markers: Regularly measure plasma ammonia, glutamine, and amino acids levels.
- Blood Chemistry: Monitor blood glucose, AST, ALT, and pH levels.
- Clinical Response: Evaluate the patient's overall response to treatment.
- Serum Electrolytes: Check potassium, chloride, and bicarbonate levels.
- Infusion Site: Ensure the infusion site is intact and free from signs of irritation or extravasation.
How to administer Ammonul (Sodium phenylacetate and sodium benzoate)?
Administration Guidelines for IV Sodium Phenylacetate and Sodium Benzoate
- Dilution: Ensure proper dilution before administration.
- Central Line Only: Administer only via a central line to prevent burning; peripheral administration may cause irritation.
- Extravasation Management: If extravasation is suspected, discontinue infusion and resume at a different site if necessary.
- Infusion Timing: Administer loading dose over 90 to 120 minutes; maintenance dose is given over 24 hours.
- Irritation Risk: Due to potential irritant and vesicant-like properties, ensure proper needle or catheter placement to avoid extravasation, which may lead to tissue necrosis.
Mechanism of action of Ammonul (Sodium phenylacetate and sodium benzoate):
- Sodium phenylacetate and sodium benzoate offer alternative pathways for eliminating ammonia by forming metabolites.
- Specifically, one mole of sodium phenylacetate removes two moles of nitrogen, while one mole of sodium benzoate removes one mole of nitrogen.
- This process helps reduce ammonia levels in the body, aiding in the treatment of conditions associated with hyperammonemia.
Metabolism:
- These compounds undergo hepatic and renal metabolism.
- 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 eliminated through urine, where the metabolites, phenylacetylglutamine and hippuric acid, are excreted.
- This process aids in the removal of excess ammonia from the body, helping to manage conditions associated with hyperammonemia.
Sodium phenylacetate and sodium benzoate Brand Names (International):
- Ammonul
Sodium phenylacetate and sodium benzoate Brand Names in Pakistan:
No Brands Available in Pakistan.
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:
- When treating hyperammonemia, start with a loading dose given slowly over 90 to 120 minutes, then switch to a continuous maintenance infusion over 24 hours.
- Begin treatment as soon as hyperammonemia is diagnosed, especially in neonates with coma, and continue until ammonia levels normalize or the patient can eat and take medications by mouth.
- The dosage depends on weight for young children and body size for older patients.
- Avoid repeating loading doses to prevent potential neurotoxic effects from prolonged high plasma levels of the medication.
- Antiemetics may be given during the infusion to help manage nausea and vomiting.
Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders:
- In the treatment of acute hyperammonemia due to urea cycle disorders, the recommended IV dose of sodium phenylacetate and sodium benzoate is 55 mL/m^2, which provides 5.5 grams/m^2 of each medication.
- This dosage should be co-administered with arginine.
- In cases of severe hyperammonemia or when the patient does not respond well to sodium phenylacetate/sodium benzoate therapy alone, hemodialysis may be considered as an adjunctive treatment.
Ammonul (Sodium phenylacetate/sodium benzoate) dose in children:
Note:
- Administer the sodium phenylacetate and sodium benzoate as a loading dose over 90 to 120 minutes, followed by an equivalent maintenance infusion over 24 hours.
- The dosage should be adjusted based on weight for infants and young children and body surface area for older children and adolescents.
- Start treatment immediately upon diagnosing hyperammonemia, and continue until ammonia levels normalize or the patient can take oral nutrition and medications.
- Antiemetics can be given during the infusion to manage nausea and vomiting.
Ammonul dose in the treatment of acute Hyperammonemia in patients with urea cycle disorders [UCD]):
In the treatment of acute hyperammonemia due to urea cycle disorders (UCD) with Ammonul (sodium phenylacetate and sodium benzoate), the dosage varies based on the weight of the patient.
- For infants and children weighing ≤20 kg, the recommended dosage is a loading dose of 2.5 mL/kg, which provides sodium phenylacetate 250 mg/kg and sodium benzoate 250 mg/kg, followed by a maintenance infusion of 2.5 mL/kg/24 hours, providing the same amounts of both medications per 24 hours.
- For children and adolescents weighing >20 kg, the loading dose is 55 mL/m^2, which provides sodium phenylacetate 5.5 g/m^2 and sodium benzoate 5.5 g/m^2, followed by a maintenance infusion of 55 mL/m^2/24 hours, providing the same amounts of both medications per 24 hours.
It's important to administer sodium phenylacetate and sodium benzoate concomitantly with arginine, with the arginine dose varying based on the type of UCD.
Pregnancy Risk Factor C
- The pregnancy risk factor C indicates that there haven't been adequate studies conducted on pregnant women, and animal reproduction studies with this combination of medications (sodium phenylacetate and sodium benzoate) haven't been carried out either.
- This classification suggests caution should be exercised when considering the use of these medications during pregnancy, and the potential benefits should be weighed against the potential risks.
Sodium phenylacetate and sodium benzoate use during breastfeeding:
- Since it's uncertain whether sodium phenylacetate and sodium benzoate are excreted in breast milk, caution is advised when administering these medications to nursing women.
- The manufacturer recommends exercising caution in such cases.
Ammonul Dose adjustment in renal disease:
- Although the manufacturer's labeling doesn't specify dosage adjustments, it's important to note that the drug metabolites and ammonia are excreted by the kidneys.
- Therefore, caution should be exercised when using sodium phenylacetate and sodium benzoate, especially in patients with impaired kidney function.
- Close monitoring is recommended to ensure proper excretion and to prevent potential adverse effects.
- Adjustments to the dosage may be necessary based on individual patient factors and renal function.
Ammonul Dose adjustment in liver disease:
- Since there are no dosage adjustments provided in the manufacturer's labeling for hepatic impairment, caution should be exercised when administering sodium phenylacetate and sodium benzoate to patients with liver dysfunction.
- Hepatic impairment can affect the metabolism and clearance of medications, potentially leading to increased drug levels and adverse effects.
- Close monitoring of liver function and clinical response is advised, and dosage adjustments may be necessary based on individual patient factors.
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):
- The absence of contraindications listed in the manufacturer's labeling indicates that there are no specific situations in which the use of sodium phenylacetate and sodium benzoate is strictly prohibited.
Warnings and Precautions
Acute hyperammonemia:
- Uncontrolled hyperammonemia can lead to severe consequences, including brain death.
- It's crucial to promptly employ all available therapies to lower ammonia levels, such as hemodialysis, caloric supplementation, and restricting dietary protein intake.
- Nonprotein calories, primarily in the form of glucose (8 to 10 mg/kg/minute), should be administered, supplemented with IV fat emulsion.
- Efforts should be made to ensure a daily caloric intake of over 80 calories per kilogram to support metabolic needs and aid in recovery.
Extravasation:
- When administering sodium phenylacetate and sodium benzoate, it's crucial to use a central line for infusion to prevent extravasation, as peripheral administration may cause burning due to its irritant properties.
- While it doesn't possess typical vesicant properties, it can still cause tissue irritation.
- If extravasation is suspected, discontinue the infusion immediately and consider resuming at a different infusion site, if necessary, to minimize the risk of local tissue damage.
Fluid overload:
- Due to its significant sodium content, sodium phenylacetate and sodium benzoate should be used cautiously, if at all, in patients who are at risk for fluid overload, such as those with heart failure or severe renal impairment, as well as those prone to sodium retention edema.
- If there are signs of clinically significant fluid overload, discontinuing the use of these medications is recommended.
- Close monitoring of fluid balance and clinical status is essential when administering sodium phenylacetate and sodium benzoate to patients with these risk factors.
Gastrointestinal effects:
- Nausea and vomiting are potential gastrointestinal side effects of sodium phenylacetate and sodium benzoate therapy.
- To mitigate these effects, premedication with antiemetics may be administered prior to infusion.
- This can help manage nausea and vomiting and improve patient tolerance to the treatment.
- Close monitoring for gastrointestinal symptoms is recommended during and after infusion, and appropriate supportive measures should be taken as needed.
Hypokalemia:
- Hypokalemia, a condition characterized by low potassium levels in the blood, is a potential side effect of sodium phenylacetate and sodium benzoate therapy.
- It's important to monitor plasma potassium levels closely during treatment and to initiate appropriate treatment if hypokalemia occurs.
Metabolic acidosis/ hyperventilation:
- The use of sodium phenylacetate and sodium benzoate may lead to hyperventilation and metabolic acidosis.
- These medications contain compounds that are structurally similar to salicylate.
- Consequently, adverse effects commonly associated with salicylate overdose, such as hyperventilation and metabolic acidosis, may occur with their use.
- It's crucial to monitor patients closely for signs of these complications during treatment and to take appropriate measures to manage them as needed.
Neurotoxicity:
- Neurotoxicity is a potential side effect of phenylacetate, manifesting as symptoms like fatigue, lightheadedness, and somnolence.
- These symptoms may occur at the beginning of treatment and typically resolve upon discontinuation of the medication.
- It's important to monitor patients closely for any signs of neurotoxicity during sodium phenylacetate and sodium benzoate therapy, and if such symptoms occur, discontinuing the treatment may be necessary to prevent further adverse effects.
Hepatic impairment:
- Given the potential impairment of the metabolism of sodium phenylacetate and sodium benzoate in patients with hepatic impairment, caution is advised when using these medications in such individuals.
- Monitoring liver function and clinical response closely is important in these cases.
- Adjustments to the dosage may be necessary based on individual patient factors and hepatic function.
Renal impairment:
- In patients with renal impairment, sodium phenylacetate and sodium benzoate should be used cautiously due to the potential reduction in the excretion of drug metabolites, such as phenylacetylglutamine and hippurate, as well as ammonia, which are primarily eliminated by the kidneys.
- Additionally, the use of these medications may predispose patients to fluid overload, further complicating renal function.
- Close monitoring of renal function and fluid status is essential, and adjustments to the dosage may be necessary based on individual patient factors and renal function.
Sodium phenylacetate and sodium benzoate: Drug Interaction
|
Probenecid |
May increase the serum concentration of Sodium Phenylacetate. Specifically, probenecid may inhibit the renal transport of the phenylacetylglutamine metabolite of sodium phenylacetate. |
|
Probenecid |
May increase the serum concentration of Sodium Benzoate. Specifically, probenecid may inhibit the renal transport of the hippuric acid metabolite of sodium benzoate. |
Monitoring parameters:
Monitoring Parameters for Hyperammonemia
- Neurologic Status: Watch for changes in alertness, behavior, or consciousness.
- Glasgow Coma Scale: Assess the level of consciousness regularly.
- Tachypnea: Monitor breathing rate for signs of respiratory distress.
- Imaging: Consider CT or MRI scans or fundoscopic examination for signs of cerebral edema or brain damage.
- Biochemical Markers: Regularly measure plasma ammonia, glutamine, and amino acids levels.
- Blood Chemistry: Monitor blood glucose, AST, ALT, and pH levels.
- Clinical Response: Evaluate the patient's overall response to treatment.
- Serum Electrolytes: Check potassium, chloride, and bicarbonate levels.
- Infusion Site: Ensure the infusion site is intact and free from signs of irritation or extravasation.
How to administer Ammonul (Sodium phenylacetate and sodium benzoate)?
Administration Guidelines for IV Sodium Phenylacetate and Sodium Benzoate
- Dilution: Ensure proper dilution before administration.
- Central Line Only: Administer only via a central line to prevent burning; peripheral administration may cause irritation.
- Extravasation Management: If extravasation is suspected, discontinue infusion and resume at a different site if necessary.
- Infusion Timing: Administer loading dose over 90 to 120 minutes; maintenance dose is given over 24 hours.
- Irritation Risk: Due to potential irritant and vesicant-like properties, ensure proper needle or catheter placement to avoid extravasation, which may lead to tissue necrosis.
Mechanism of action of Ammonul (Sodium phenylacetate and sodium benzoate):
- Sodium phenylacetate and sodium benzoate offer alternative pathways for eliminating ammonia by forming metabolites.
- Specifically, one mole of sodium phenylacetate removes two moles of nitrogen, while one mole of sodium benzoate removes one mole of nitrogen.
- This process helps reduce ammonia levels in the body, aiding in the treatment of conditions associated with hyperammonemia.
Metabolism:
- These compounds undergo hepatic and renal metabolism.
- 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 eliminated through urine, where the metabolites, phenylacetylglutamine and hippuric acid, are excreted.
- This process aids in the removal of excess ammonia from the body, helping to manage conditions associated with hyperammonemia.
Sodium phenylacetate and sodium benzoate Brand Names (International):
- Ammonul
Sodium phenylacetate and sodium benzoate Brand Names in Pakistan:
No Brands Available in Pakistan.
 Injection.webp)