AMMONUL
Clinical safety rating
cautionComprehensive clinical and safety monograph for AMMONUL (AMMONUL).
Ammonul (sodium phenylacetate and sodium benzoate) provides an alternative pathway for nitrogen excretion. Phenylacetate conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Benzoate conjugates with glycine to form hippurate, which is also excreted renally. This reduces ammonia levels in patients with urea cycle disorders.
| Metabolism | Sodium phenylacetate is metabolized via conjugation with glutamine (by glutamine N-phenylacetyltransferase) to form phenylacetylglutamine. Sodium benzoate is metabolized via conjugation with glycine (by benzoyl-CoA:glycine N-acyltransferase) to form hippurate. Both conjugates are rapidly excreted by the kidneys. |
| Excretion | Renal: >80% (primarily as phenylacetylglutamine). Biliary/fecal: <5%. |
| Half-life | Phenylacetate: 0.5-1 hour; phenylacetylglutamine: 1-2 hours. Clinical context: rapid clearance; requires continuous IV infusion for sustained effect. |
| Protein binding | Phenylacetate: 82% bound to albumin; phenylacetylglutamine: 51% bound. |
| Volume of Distribution | Phenylacetate: 0.3-0.5 L/kg; phenylacetylglutamine: 0.1-0.2 L/kg. Indicates distribution primarily in extracellular fluid. |
| Bioavailability | Oral: Not available; sodium phenylacetate/sodium benzoate is administered intravenously only. |
| Onset of Action | Intravenous: Within 2 hours for reduction in plasma ammonia levels. |
| Duration of Action | Ammonia-lowering effect lasts 4-6 hours after infusion ends; requires continuous or repeated dosing. |
| Molecular Weight | 208.19 |
For acute hyperammonemia: 2.5 g/m² IV over 90 minutes, followed by continuous IV infusion at 2.5 g/m² over 24 hours. For maintenance: 2.5 g/m² IV or oral every 6 hours.
| Dosage form | SOLUTION |
| Renal impairment | Contraindicated in severe renal insufficiency (CrCl <30 mL/min). For moderate impairment (CrCl 30-50 mL/min): reduce dose by 50%. For mild impairment (CrCl 50-80 mL/min): no adjustment needed. |
| Liver impairment | No specific guidelines based on Child-Pugh; use with caution in severe hepatic impairment. Monitor ammonia levels. |
| Pediatric use | Same weight-based area (2.5 g/m²) as adults. For neonates and infants, dosage calculated per body surface area. Administration route and frequency identical to adults. |
| Geriatric use | No specific dose adjustment; use caution due to age-related renal decline. Monitor renal function and ammonia levels. |
| 1st trimester | Limited human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; no known fetal harm. Monitor maternal and fetal status. |
| 3rd trimester | May be used for management of urea cycle disorders; avoid hyperammonemia which can harm fetus. |
Clinical note
Comprehensive clinical and safety monograph for AMMONUL (AMMONUL).
| Placental transfer | Sodium phenylacetate and sodium benzoate cross the placenta; extent unknown. |
| Breastfeeding | Sodium phenylacetate and sodium benzoate are excreted into breast milk in low amounts. Consider risk-benefit; monitor infant for potential adverse effects. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Pregnancy Category C. No adequate human studies; in animal studies, sodium phenylacetate/sodium benzoate caused fetal toxicity at maternally toxic doses. First trimester: potential risk unknown; second/third trimester: may cause maternal ammonia accumulation if subtherapeutic, but drug is essential for urea cycle disorders. Risk of untreated hyperammonemia outweighs potential teratogenic risk. |
| Fetal Monitoring | Monitor plasma ammonia levels, serum electrolytes (sodium, potassium, bicarbonate), blood pH, liver and renal function in mother. For fetus: growth scans and fetal monitoring during third trimester if maternal instability. |
| Fertility Effects | No known effect on human fertility; animal studies not reported. Urea cycle disorders may impact fertility indirectly via metabolic control. |
■ FDA Black Box Warning
Ammonul must be administered with arginine to prevent arginine deficiency and worsening hyperammonemia. Neurotoxicity (including seizures, cerebral edema, and death) may occur if not properly monitored. Extravasation can cause severe tissue necrosis; ensure proper IV access.
| Serious Effects |
Hypersensitivity to any component
| Precautions | Monitor plasma ammonia levels, electrolytes, and blood counts closely., Risk of hypernatremia (high sodium load); adjust fluid and sodium intake., Extravasation risk: administer through a central line if possible; treat extravasation immediately., May cause hyperventilation and metabolic acidosis., Use with caution in patients with hepatic or renal impairment., Contains sodium benzoate; possible hypersensitivity reactions. |
| Food/Dietary | Take with food or meals to reduce gastrointestinal distress. Avoid high-protein supplements or foods that may increase ammonia levels; dietary protein restriction should be managed by a dietitian. |
| Clinical Pearls | AMMONUL (sodium phenylbutyrate) is used as a nitrogen-binding agent in urea cycle disorders. Monitor plasma ammonia levels closely; target <60 μmol/L. Administer with food to reduce GI irritation. Not recommended in patients with severe hepatic impairment due to reduced conversion to phenylacetate. Contraindicated in pregnancy (category C). |
| Patient Advice | Take exactly as prescribed; do not skip doses. · May cause nausea, vomiting, or diarrhea; take with food. · Avoid use of valproic acid or corticosteroids unless directed. · Contact provider if symptoms of hyperammonemia occur (vomiting, lethargy, confusion). · Women of childbearing potential should use effective contraception. · Store at room temperature away from moisture. |
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