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Arginine: Drug information

Arginine: Drug information
(For additional information see "Arginine: Patient drug information" and see "Arginine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • R-Gene 10
Pharmacologic Category
  • Diagnostic Agent
Dosing: Adult
Diagnostic aid

Diagnostic aid (pituitary function): Note: Dosing based on arginine hydrochloride product. IV: 30 g as a single dose.

Hyperammonemia, acute

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

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).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Pediatric

(For additional information see "Arginine: Pediatric drug information")

Hyperammonemia, acute

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

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

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

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.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution; use may lead to life-threatening hyperkalemia.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution; use may lead to life-threatening hyperkalemia.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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]

Generic Equivalent Available: US

No

Dosage Forms Considerations

R-Gene 10 contains chloride 47.5 mEq per 100 mL

Administration: Adult

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).

Administration: Pediatric

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.

Use: Labeled Indications

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.

Use: Off-Label: Adult

Hyperammonemia (acute) associated with urea cycle disorders; Urea cycle disorders (chronic therapy)

Medication Safety Issues
Administration issues:

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.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Diagnostic aid:

1% to 10%:

Cardiovascular: Flushing, venous irritation

Gastrointestinal: Nausea, vomiting

Nervous system: Headache, numbness

<1%:

Hematologic & oncologic: Decreased platelet count

Hypersensitivity: Hypersensitivity reaction

Hyperammonemia, acute:

>10%:

Hematologic & oncologic: Hematologic abnormality (11%; including anemia [4%], disorder of hemostatic components of blood [<3%], disorder of the lymphatic system, disseminated intravascular coagulation [3%], hemorrhage [<3%], pancytopenia [<3%], and thrombocytopenia [<3%])

Infection: Infection (12%; including sepsis [<3%], septic shock [<3%], and urinary tract infection [3%])

Nervous system: Central nervous system dysfunction (22%; including absent reflexes [<3%], ataxia [<3%], brain edema [5%], cerebral atrophy [<3%], cerebral hemorrhage [<3%], cerebral infarction [<3%], clonus [<3%], coma [3%], decreased mental acuity [6%], encephalopathy [<3%], impaired consciousness [<3%], increased intracranial pressure [<3%], paralysis [nerve: <3%], seizure [6%], and tremor [<3%])

Respiratory: Respiratory system disorder (15%; including acute respiratory distress syndrome [<3%], dyspnea [<3%], hypercapnia [<3%], hyperventilation [<3%], Kussmaul respiration [<3%], pulmonary edema [<3%], pulmonary hemorrhage [<3%], respiratory acidosis [<3%], respiratory alkalosis [<3%], respiratory distress [3%], respiratory failure [<3%], tachypnea [<3%], and variations in blood CO2 concentrations [<3%])

1% to 10%:

Cardiovascular: Cardiac disorder (9%; including acute cardiorespiratory failure [<3%], bradycardia [<3%], cardiogenic shock [<3%], cardiomyopathy [<3%], heart failure [<3%], myocardial rupture [atrial: <3%], and pericardial effusion [<3%]), chest pain (<3%), edema (<3%), hypertension (<3%), hypotension (4%), low cardiac output (<3%), vascular disease (6%; including flushing [<3%], thrombosis [<3%], and venous thrombosis [<3%])

Dermatologic: Dermatological disorder (6%; including alopecia [<3%], pruritus [<3%], skin blister [<3%], skin rash [<3%], and urticaria [<3%])

Endocrine & metabolic: Acidosis (3%), alkalosis (<3%), dehydration (<3%), fluid retention (<3%), hyperglycemia (7%), hypernatremia (<3%), hypocalcemia (3%), hypoglycemia (<3%), hypokalemia (7%), increased serum pH (<3%), metabolic acidosis (4%)

Gastrointestinal: Abdominal distention (<3%), cholestasis (<3%), diarrhea (3%), gastrointestinal hemorrhage (<3%), nausea (3%, vomiting (9%)

Hepatic: Hepatic artery stenosis (<3%), hepatic failure (<3%), hepatotoxicity (<3%), jaundice (<3%)

Local: Injection-site reaction (3%)

Nervous system: Asthenia (<3%), cerebral herniation (<3%), psychiatric disturbance (5%; including acute psychosis [<3%], aggressive behavior [<3%], agitation [3%], confusion [<3%], and hallucination [<3%]), subdural hematoma (<3%)

Neuromuscular & skeletal: Tetany (<3%)

Ophthalmic: Blindness (<3%)

Renal: Renal disease (4%; including anuria [<3%], renal failure syndrome [<3%], and urinary retention [<3%])

Miscellaneous: Fever (5%), multi-organ failure (<3%)

Postmarketing (any indication):

Endocrine & metabolic: Hyperkalemia (Bushinsky 1978)

Gastrointestinal: Esophagitis (Parra 2020), pancreatitis (Binet 2018)

Genitourinary: Hematuria (Glibbery 2020)

Hypersensitivity: Anaphylaxis, nonimmune anaphylaxis (Resnick 2002)

Contraindications

Hypersensitivity to arginine or any component of the formulation

Warnings/Precautions

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.

Warnings: Additional Pediatric Considerations

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).

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

Teratogenic effects were not observed in animal studies; however, the manufacturer does not recommend use of arginine during pregnancy.

Breastfeeding Considerations

Amino acids are present in breast milk, the amount following arginine administration is not known.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics

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)

Pricing: US

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.

Brand Names: International
  • Arginina (PL);
  • Rocmaline (FR)


For country code abbreviations (show table)
  1. Ah Mew N, Simpson KL, Gropman AL, Lanpher BC, Chapman KA, Summar ML. Urea cycle disorders overview. In: Adam MP, Ardinger HH, Pagon RA, et al editors. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2017. http://www.ncbi.nlm.nih.gov/books/NBK1217/. Published April 29, 2003. Updated June 22, 2017. [PubMed 20301396]
  2. Amin HJ, Zamora SA, McMillan DD, et al, "Arginine Supplementation Prevents Necrotizing Enterocolitis in the Premature Infant," J Pediatr, 2002, 140(4):425-31. [PubMed 12006956]
  3. Ammonul (sodium phenylacetate and sodium benzoate) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; December 2016.
  4. Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr. 2001;138(1 Suppl):S46-54. [PubMed 11148549]
  5. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr. 2001;138(1 Suppl):S56-60. [PubMed 11148550]
  6. Binet Q, Dufour I, Agneessens E, et al. The second case of a young man with L-arginine-induced acute pancreatitis. Clin J Gastroenterol. 2018;11(5):424-427. doi:10.1007/s12328-018-0862-4 [PubMed 29680982]
  7. Bode-Boger SM, Boger RH, Galland A, Tsikas D, Frolich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998;46(5):489-497. [PubMed 9833603]
  8. Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr. 1996;43:127-170. [PubMed 8794176]
  9. Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med. 1978;89(5 Pt 1):632-634. doi:10.7326/0003-4819-89-5-632 [PubMed 717931]
  10. Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr. 2007;137(6 Suppl 2):1646S-1649S. [PubMed 17513441]
  11. Enns GM, Berry SA, Berry GT, Rhead WJ, Brusilow SW, Hamosh A. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med. 2007;356(22):2282-2292. [PubMed 17538087]
  12. Glibbery M, Fleming A, Chanchlani R, et al. Myalgia and hematuria in association with clonidine and arginine administration for growth hormone stimulation tests. Case Rep Med. 2020;2020:4827072. doi:10.1155/2020/4827072 [PubMed 32547619]
  13. Häberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. J Inherit Metab Dis. 2019;42(6):1192-1230. doi:10.1002/jimd.12100 [PubMed 30982989]
  14. Leonard JV, Morris AA. Urea cycle disorders. Semin Neonatol. 2002;7(1):27-35. [PubMed 12069536]
  15. Martin WJ and Matzke GR, "Treating Severe Metabolic Alkalosis," Clin Pharm, 1982, 1(1):42-8. [PubMed 6764161]
  16. Nagamani SCS, Erez A, Lee B. Argininosuccinate lyase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2017. Published February 3, 2011. Updated March 2019. http://www.ncbi.nlm.nih.gov/books/NBK51784/ [PubMed 21290785]
  17. National Organization for Rare Disorders (NORD). The Physician's Guide to Urea Cycle Disorders. Danbury, CT: National Organization for Rare Disorders; 2013.
  18. National Urea Cycle Disorders Foundation. Available at http://www.nucdf.org/medical_information.htm.
  19. Parra PR, González-Cruz MÁ, Ferreiro-Marin A, Casaubón-Garcín PR. L-arginine-induced esophagitis, report of six cases. Bol Med Hosp Infant Mex. 2020;77(1):38-41. doi:10.24875/BMHIM.19000109 [PubMed 32115583]
  20. Resnick DJ, Softness B, Murphy AR, Aranoff GS, Levine LS. Case report of an anaphylactoid reaction to arginine. Ann Allergy Asthma Immunol. 2002;88(1):67-68. doi:10.1016/S1081-1206(10)63596-X [PubMed 11814282]
  21. Reynolds PM, MacLaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014;34(6):617-632. doi: 10.1002/phar.1396. [PubMed 24420913]
  22. R-Gene 10 (arginine) [prescribing information]. New York, NY: Pharmacia and Upjohn; August 2021.
  23. Schulman SP, Becker LC, Kass DA, L-Arginine Therapy in Acute Myocardial Infarction. The Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial, JAMA, 2006, 295(1):58-64. [PubMed 16391217]
  24. Shah P and Shah V, "Arginine Supplementation for Prevention of Necrotising Enterocolitis in Preterm Infants," Cochrane Database Syst Rev, 2007, (3):CD004339. [PubMed 17636753]
  25. Summar M, “Current Strategies for the Management of Neonatal Urea Cycle Disorders,” J Pediatr, 2001, 138(1 Suppl):S30-9. [PubMed 11148547]
  26. Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. 1999;47(3):261-266. [PubMed 10215749]
  27. Urea Cycle Disorders Conference Group. Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr. 2001;138(1 Suppl):S1-5. [PubMed 11148543]
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