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Arginine

Medically reviewed by Drugs.com. Last updated on May 29, 2023.

Pronunciation

(AR ji neen)

Index Terms

Dosage Forms

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]

Brand Names: U.S.

Pharmacologic Category

Pharmacology

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 2011)

Excretion

Urine (16% during the first 90 minutes; biphasic elimination) (Tangphao 1999)

Time to Peak

Serum: Oral: ~2 hours; IV: 22 to 30 minutes (Bode-Boger 1998; Tangphao 1999)

Half-Life Elimination

42 ± 2 minutes following a 30 g IV dose; exhibits nonlinear, dose-dependent elimination (Tangphao 1999)

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.

Off Label Uses

Hyperammonemia (acute) associated with urea cycle disorders

Data from an uncontrolled open-label study conducted over a 25 year period supports the use of intravenous arginine (in combination with sodium benzoate, sodium phenylacetate and adequate caloric provision) for the treatment of acute hyperammonemia associated with urea-cycle disorders resulting in increased survival [Enns 2007]. Clinical experience also suggests the utility of intravenous arginine for the management of this condition [Batshaw 2001].

Based on the National Organization for Rare Disorders, the use of arginine (in combination with sodium benzoate, sodium phenylacetate and adequate caloric provision) is effective and recommended for the management of patients with this condition.

Urea cycle disorders (chronic therapy)

Clinical experience suggests the utility of oral arginine for the long-term chronic management of this condition [Batshaw 2001], [Berry 2001], [Brusilow 1996].

Based on the National Organization for Rare Disorders, the use of arginine is effective and recommended for the management of patients with this condition.

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).

Contraindications

Hypersensitivity to arginine or any component of the formulation

Dosing: Adult

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 2012).

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 2012)

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 2012)

Unconfirmed/pending diagnosis: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (NORD 2012); 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 2012; NORD 2012)

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 2012; NORD 2012)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

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.

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 2012). 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 2012).

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 2012).

Unconfirmed/pending diagnosis: IV: Loading dose: 600 mg/kg followed by a continuous IV infusion of 600 mg/kg/day (NORD 2012). 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)

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 2012):

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 2012):

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

Administration

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 (NORD 2012; Ah Mew 2017); 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).

Storage

Store at 25°C (77°F). Do not use if frozen. Once the vial has been punctured, may store for up to 4 hours at 25°C (77°F) (including infusion time) or 24 hours at 2°C to 8°C.

Drug Interactions

There are no known significant interactions.

Arginine drug interactions (more detail)

Adverse Reactions

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)

Arginine side effects (more detail)

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.

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.

Pregnancy Considerations

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

Patient Education

What is this drug used for?

• It is used to check the pituitary gland's function.

• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe injection site pain, redness, burning, or irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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