Diagnostic aid (pituitary function): Note: Dosing based on arginine hydrochloride product. IV: 30 g as a single dose.
Hyperammonemia, acute (urea cycle disorders) (off-label use): Note: Dosing based on arginine hydrochloride product and on specific enzyme deficiency. Therapy should continue until ammonia levels are in normal range. If a loading dose is used, it should not be repeated. Arginine dose may be adjusted downward if patient becomes hypotensive and/or when the exact enzyme deficiency is identified. Administer concomitantly with sodium benzoate and sodium phenylacetate along with dialysis (NORD 2013).
Weight-directed dosing:
Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL) deficiency: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (NORD 2013).
Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetylglutamate synthetase (NAGS) deficiency: IV: Loading dose: 200 mg/kg followed by a continuous IV infusion of 200 mg/kg/day (NORD 2013).
Unconfirmed/pending diagnosis: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (NORD 2013); if ASS and ASL are excluded as diagnostic possibilities, reduce dose to 200 mg/kg/day.
BSA-directed dosing:
Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL) deficiency: IV: Loading dose: 12 g/m2 followed by a continuous IV infusion of 12 g/m2/day (Ah Mew 2017).
Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC) deficiency: IV: Loading dose: 4 g/m2 followed by a continuous IV infusion of 4 g/m2/day (Ah Mew 2017).
Urea cycle disorders, chronic therapy (off-label use): Oral: Note: Dosing based on arginine free base powder product:
Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL) deficiency: 0.4 to 0.7 g/kg/day or 8.8 to 15.4 g/m2/day in 3 to 4 divided doses (Nagamani 2019; NORD 2013).
Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC) deficiency: 2.5 to 6 g/m2/day in 3 or 4 divided doses (maximum: 6 g/day) has been recommended however, citrulline may be preferred therapy (Häberle 2019; NORD 2013).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
(For additional information see "Arginine: Pediatric drug information")
Hyperammonemia, acute (urea cycle disorders): Limited data available: Infants, Children, and Adolescents:
Note: Administered concomitantly with sodium benzoate and sodium phenylacetate. Dosage based on specific enzyme deficiency; therapy should continue until ammonia levels are in normal range. If patient already receiving arginine therapy, consider either a reduction in the loading dose or possible elimination (Batshaw 2001); if a loading dose is used, it should not be repeated (NORD 2013). Note: Dosing based on arginine hydrochloride product.
Weight-directed dosing:
Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (Ah Mew 2017; Batshaw 2001; NORD 2013).
Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetylglutamate synthetase (NAGS) deficiency: IV: Loading dose: 200 mg/kg followed by a continuous IV infusion of 200 mg/kg/day (Ah Mew 2017; Batshaw 2001; NORD 2013).
Unconfirmed/pending diagnosis: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (NORD 2013). If ASS and ASL are excluded as diagnostic possibilities, reduce dose to 200 mg/kg/day.
BSA-directed dosing:
Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency: IV: Loading dose: 12 g/m2 followed by a continuous IV infusion of 12 g/m2/day (Ah Mew 2017; Batshaw 2001; Brusilow 1996).
Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC) disorder: IV: Loading dose: 4 g/m2 followed by a continuous IV infusion of 4 g/m2/day (Ah Mew 2017; Batshaw 2001; Brusilow 1996).
Metabolic alkalosis: Limited data available: Infants, Children, and Adolescents: IV:
Note: Arginine hydrochloride is an alternative treatment for uncompensated metabolic alkalosis after sodium chloride and potassium chloride supplementation have been optimized; it should not be used as initial therapy for chloride supplementation. Each 1 g of arginine hydrochloride provides 4.75 mEq chloride. Note: Dosing based on arginine hydrochloride product.
Arginine hydrochloride dose (mEq) = 0.5 x weight (kg) x [HCO3- - 24] where HCO3- = the patient's serum bicarbonate concentration in mEq/L (Martin 1982); give 1/2 to 2/3 of calculated dose and reevaluate.
To correct hypochloremia: Arginine hydrochloride dose (mEq) = 0.2 x weight (kg) x [103 - Cl-] where Cl- = the patient's serum chloride concentration in mEq/L (Martin 1982); give 1/2 to 2/3 of calculated dose and reevaluate.
Pituitary function test: Note: Dosing based on arginine hydrochloride product: Infants, Children, and Adolescents: IV: 0.5 g/kg over 30 minutes; maximum dose: 30 g dose.
Urea cycle disorders, chronic therapy: Limited data available: Infants, Children, and Adolescents: Note: Dose should be individualized based on patient response; doses may need to be increased by ~50% as part of a sick-day routine (Berry 2001): Note: Dosing based on arginine-free base powder product:
Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency (Batshaw 2001; Berry 2001; Brusilow 1996; NORD 2013):
Weight-directed dosing: Oral: 400 to 700 mg/kg/day in 3 to 4 divided doses.
BSA-directed dosing: Oral: 8.8 to 15.4 g/m2/day in 3 to 4 divided doses.
Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetylglutamate synthetase (NAGS) deficiency: Note: Citrulline may be preferred for some patients (Batshaw 2001; Brusilow 1996; NORD 2013):
Weight-directed dosing: Oral: 170 mg/kg/day in 3 to 4 divided doses.
BSA-directed dosing: Oral: 3.8 g/m2/day in 3 to 4 divided doses.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution; use may lead to life-threatening hyperkalemia.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution; use may lead to life-threatening hyperkalemia.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride [preservative free]:
R-Gene 10: 10% (300 mL) [latex free]
No
R-Gene 10 contains chloride 47.5 mEq per 100 mL
IV: Administer undiluted over 30 minutes. For doses <30 g (<300 mL), the manufacturer recommends transferring the dose to a separate container prior to administration. Prolongation of the infusion period may diminish the stimulus to the pituitary and nullify the test. In the treatment of hyperammonemia associated with urea cycle disorders (off-label use), administer loading dose over 90 to 120 minutes (Ah Mew 2017; NORD 2013); maintenance infusion should not exceed 150 mg/kg/hour (Ah Mew 2017).
Irritant with vesicant-like properties; ensure proper catheter placement prior to and during infusion; avoid extravasation. Some recommend infusion through central access only (Ah Mew 2017).
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote (if indicated); remove needle/cannula; elevate extremity. Apply dry cold compresses (Reynolds 2014).
Hyaluronidase: Intradermal: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections to border of extravasation area (Reynolds 2014).
Oral, powder: Arginine free base: Take with meals and space doses evenly throughout the day. Oral products available in the US are often marketed as dietary supplements. When using these products, patients should take care to ensure that they are receiving pharmaceutical grade supplements of L-arginine and verify the formulation (free base vs arginine HCl). The National Urea Cycle Disorders Foundation cautions against using oral dietary supplements of arginine HCl (National Urea Cycles Disorder Foundation).
IV: Arginine hydrochloride:
Pituitary function test: Administer undiluted over 30 minutes. For doses <30 g (<300 mL), the manufacturer recommends transferring the dose to a separate container prior to administration.
Hyperammonemia, acute (urea cycle disorders): May administer in combination with sodium benzoate and sodium phenylacetate injection; central line preferred. Administer loading dose over 90 to 120 minutes (Ah Mew 2017; UCD conference group 2001).
Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation. Some recommend infusion through central access only (Ah Mew 2017; UCD conference group 2001). If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote (see Management of Drug Extravasations for more details); remove needle/cannula; elevate extremity. Apply dry cold compresses (Reynolds 2014).
Oral, powder: Arginine-free base: Take with meals and space doses evenly throughout the day.
Diagnostic aid: As an intravenous (IV) stimulant to the pituitary for the release of human growth hormone (hGH) in patients in whom the measurement of pituitary reserve for hGH can be of diagnostic usefulness. Used as a diagnostic aid in such conditions as panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism, and problems of growth and stature.
Hyperammonemia (acute) associated with urea cycle disorders; Urea cycle disorders (chronic therapy)
The Food and Drug Administration (FDA) has identified several cases of fatal arginine overdose in children and has recommended that healthcare professionals always recheck dosing calculations prior to administration of arginine. Doses used in children should not exceed usual adult doses.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
1% to 10%:
Cardiovascular: Flushing (with rapid IV infusion), venous irritation
Central nervous system: Headache, numbness
Gastrointestinal: Nausea, vomiting
<1%, postmarketing and/or case reports: Anaphylaxis, burning sensation of skin (due to extravasation), cerebral edema, hematuria, hyperkalemia, hypersensitivity reaction, injection site reaction, lethargy, loss of consciousness, oral paresthesia, skin necrosis (due to extravasation)
Hypersensitivity to arginine or any component of the formulation
Concerns related to adverse effects:
• Extravasation: Irritant with vesicant-like properties. Due to the hypertonicity of the IV solution, administer via IV infusion only with a patent catheter placed within a patent vein. Extravasation has resulted in burn-like reactions and skin necrosis requiring surgical intervention. Excessive rates of infusion (eg, <30 minutes) may result in local irritation.
• Hypersensitivity reactions: Severe reactions, including anaphylaxis, have been reported; if hypersensitivity occurs, discontinue and institute supportive treatment measures.
• Infusion-related reactions: Excessive rates of infusion (eg, <30 minutes) may result in flushing, nausea, or vomiting.
Disease-related concerns:
• Electrolyte imbalance: Use with caution in patients with electrolyte imbalance due to chloride content of product.
• Renal impairment: Arginine metabolism results in excretion of nitrogen-containing products. Use with caution in patients with renal impairment; decreased excretion may result in an increased amino acid or nitrogen burden.
Special populations:
• Pediatric: Fatal overdose of arginine in pediatric patients has been reported. Exercise extreme caution when infusing arginine. Overdosage of arginine in children can also result in hyperchloremic metabolic acidosis or cerebral edema.
In neonates, infants, and children overdosage has resulted in hyperchloremic metabolic acidosis, cerebral edema, or possibly death; each 1 mEq chloride delivers 1 mEq hydrogen; monitor acid base balance closely, particularly in neonates. Arginine hydrochloride is metabolized to nitrogen-containing products for excretion; the temporary effect of a high nitrogen load on the kidneys should be evaluated. Accumulation of excess arginine may result in an overproduction of nitric oxide, leading to vasodilation and hypotension (Summar 2001).
Oral products available in the US are often marketed as dietary supplements. When using these products, patients should take care to ensure that they are receiving pharmaceutical grade supplements of L-arginine and verify the formulation (free base vs arginine HCl). The National Urea Cycle Disorders Foundation cautions against using oral dietary supplements of arginine HCL (National Urea Cycles Disorder Foundation).
None known.
There are no known significant interactions.
Teratogenic effects were not observed in animal studies; however, the manufacturer does not recommend use of arginine during pregnancy.
Amino acids are present in breast milk, the amount following arginine administration is not known.
Acid-base status (arterial or capillary blood gases), serum electrolytes (sodium, potassium, chloride, bicarbonate, phosphorous), BUN, glucose, plasma amino acids, ammonia, blood pressure (patients with hyperammonemia associated with urea cycle disorders [off-label use]). Monitor infusion site.
Stimulates pituitary release of growth hormone and prolactin through origins in the hypothalamus; patients with impaired pituitary function have lower or no increase in plasma concentrations of growth hormone after administration of arginine. In patients with urea cycle disorders, the formation of arginine is prohibited; therefore, exogenous administration of arginine is required.
Absorption: Oral: Well absorbed
Distribution: Vd: ~33 L/kg following a 30 g IV dose
Metabolism: Extensively metabolized in the liver and intestines (Cynober 2007)
Bioavailability: Oral: ~68%
Half-life, elimination: 42 ± 2 minutes following a 30 g IV dose; exhibits nonlinear, dose-dependent elimination (Tangphao 1999)
Time to peak, serum: Oral: ~2 hours; IV: 22 to 30 minutes (Bode-Boger 1998; Tangphao 1999)
Excretion: Urine (16% during the first 90 minutes; biphasic elimination) (Tangphao 1999)
Solution (R-Gene 10 Intravenous)
10% (per mL): $0.16
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.