DOSAGE AND ADMINISTRATION
Administration must be through a central line. Administration through a peripheral line may cause burns.
General
AMMONUL® is administered intravenously as a loading dose infusion administered over 90 to 120 minutes, followed by an equivalent maintenance dose infusion administered over 24 hours. AMMONUL® may not be administered by any other route. Administration of analogous oral drugs, such as Buphenyl® (sodium phenylbutyrate), should be terminated prior to AMMONUL® infusion.
Hyperammonemic coma (regardless of cause) in the newborn infant should be aggressively treated while the specific diagnosis is pursued. All patients should be promptly hemodialyzed as the procedure of choice using the largest catheters consistent with the patient's size. A target blood flow of 150 mL/min/m2 may be attained using a 7F catheter. (Ammonia clearance [mL/min] is similar to the blood flow rate [mL/min] through the dialyzer). Clearance of ammonia is approximately ten times greater by hemodialysis than by peritoneal dialysis or hemofiltration. Exchange transfusion is ineffective in the management of hyperammonemia. Hemodialysis may be repeated until the plasma ammonia level is stable at normal or near normal levels.
AMMONUL® infusion should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. Non-protein calories should be supplied principally as glucose (8–10 mg/kg/min) with Intralipid added. Attempts should be made to maintain a caloric intake of greater than 80 cal/kg/d. During and after infusion of AMMONUL®, ongoing monitoring of neurological status, plasma ammonia levels, clinical laboratory values, and clinical responses are crucial to assess patient response to treatment. The need for other interventions to control hyperammonemia must be considered throughout the course of treatment. Patients with a large ammonia burden or who are not responsive to AMMONUL® administration require aggressive therapy including hemodialysis (see WARNINGS).
AMMONUL® must be diluted with sterile Dextrose Injection, 10% (D10W) before administration. The dilution and dosage of AMMONUL® are determined by weight for neonates, infants and young children, and by body surface area for larger patients, including older children, adolescents, and adults (Table 3). Maintenance infusions may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications.
AMMONUL® solutions are physically and chemically stable for up to 24 hours at room temperature and room lighting conditions. No compatibility information is presently available for AMMONUL® infusion solutions except for Arginine HCl Injection, 10%, which may be mixed in the same container as AMMONUL®. Other infusion solutions and drug products should not be administered together with AMMONUL® infusion solution. AMMONUL® solutions may be prepared in glass and PVC containers. AMMONUL® solutions should be inspected visually for particulate matter and discoloration before administration.
Table 3 Dosage and Administration | Patient Population | Components of Infusion Solution
AMMONUL® must be diluted with sterile dextrose injection 10% at ≥ 25 mL/Kg before administration. | Dosage Provided |
|---|
| AMMONUL® | Arginine HCl Injection, 10% | Sodium Phenylacetate | Sodium Benzoate | Arginine HCl |
|---|
| 0 to 20 kg: |
| CPS and OTC Deficiency |
| Dose | | | | | |
| Loading: over 90 to 120 minutes | 2.5 mL/kg | 2.0 mL/kg | 250 mg/kg | 250 mg/kg | 200 mg/kg |
| Maintenance: over 24 hours | | | | | |
| ASS and ASL Deficiency |
| Dose | | | | | |
| Loading: over 90 to 120 minutes | 2.5 mL/kg | 6.0 mL/kg | 250 mg/kg | 250 mg/kg | 600 mg/kg |
| Maintenance: over 24 hours | | | | | |
| > 20 kg: |
| CPS and OTC Deficiency |
| Dose | | | | | |
| Loading: over 90 to 120 minutes | 55 mL/m2 | 2.0 mL/kg | 5.5 g/m2 | 5.5 g/m2 | 200 mg/kg |
| Maintenance: over 24 hours | | | | | |
| ASS and ASL Deficiency |
| Dose | | | | | |
| Loading: over 90 to 120 minutes | 55 mL/m2 | 6.0 mL/kg | 5.5 g/m2 | 5.5 g/m2 | 600 mg/kg |
| Maintenance: over 24 hours | | | | | |
Arginine Administration
Intravenous arginine is an essential component of therapy for patients with carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or argininosuccinate lyase (ASL) deficiency. Because a hyperchloremic acidosis may ensue after high-dose arginine hydrochloride administration, plasma levels of chloride and bicarbonate should be monitored and appropriate amounts of bicarbonate administered.
Pending a specific diagnosis, intravenous arginine (6 mL/kg of Arginine HCl Injection, 10%, over 90 minutes followed by the same dose over 24 hours) should be given to hyperammonemic infants suspected of having a urea cycle disorder for two reasons: 1) infants with deficiencies in enzymes of the urea cycle (apart from arginase deficiency) are usually arginine-deficient; 2) hyperammonemia in infants with ASS or ASL deficiency usually respond favorably to arginine administration. If deficiencies of ASS or ASL are excluded as diagnostic possibilities, the intravenous dose of arginine HCl should be reduced to 2 mL/kg/d Arginine HCl Injection, 10%.
Converting To Oral Treatment
Once elevated ammonia levels have been reduced to the normal range, oral therapy, such as sodium phenylbutyrate, dietary management and protein restrictions should be started or reinitiated.
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