(AR ji neen)
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.
Hypersensitivity to arginine or any component of the formulation
Diagnostic aid (pituitary function): Note: Dosing based on arginine hydrochloride product. IV: 30 g as a single dose
Refer to adult dosing.
Diagnostic aid (pituitary function): Note: Dosing based on arginine hydrochloride product.
Infants, Children, and Adolescents <60 kg: IV: 0.5 g/kg as a single dose; (maximum dose: 30 g/dose)
Children and Adolescents ≥60 kg: Refer to adult dosing
Hyperammonemia, acute (urea cycle disorders) (off-label use): 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). 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 (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 (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 (Batshaw 2001; Brusilow 1996).
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 (Batshaw 2001; Brusilow 1996).
Urea cycle disorders, chronic therapy (off-label use): 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). Dosing based on arginine free base powder product:
Weight-directed dosing:
Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency: Oral: 400 to 700 mg/kg/day in 3 to 4 divided doses (Batshaw 2001; Berry 2001; Brusilow 1996; NORD 2012)
Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetylglutamate synthetase (NAGS) deficiency:Note: Citrulline may be preferred for some patients: Oral: 170 mg/kg/day in 3 to 4 divided doses (Batshaw, 2001; Brusilow 1996; NORD 2012)
BSA-directed dosing:
Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency: Oral: 8.8 to 15.4 g/m2/day in 3 to 4 divided doses (Batshaw 2001; Berry 2001; Brusilow 1996; NORD 2012)
Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetylglutamate synthetase (NAGS) deficiency:Note: Citrulline may be preferred for some patients: Oral: 3.8 g/m2/day in 3 to 4 divided doses (Batshaw, 2001; Brusilow 1996; NORD 2012)
There are no dosage adjustments provided in the manufacturers labeling; use with caution.
There are no dosage adjustments provided in the manufacturers labeling; use with caution.
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.
May be an irritant; ensure proper catheter placement prior to and during infusion; avoid extravasation.
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).
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).
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)
There are no known significant interactions.
Acid-base status (arterial or capillary blood gases), serum electrolytes (sodium, potassium, chloride, bicarbonate, phosphorous), BUN, glucose, infusion site
Frequency not defined.
1% to 10%:
Cardiovascular: Flushing (with rapid IV infusion), venous irritation
Central nervous system: Headache, numbness
Gastrointestinal: Nausea, vomiting
<1% (Limited to important or life-threatening): 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)
Concerns related to adverse effects:
- Extravasation/Infusion-related reactions: Due to the hypertonicity of the 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, flushing, nausea, or vomiting.
- Hypersensitivity reactions: Severe reactions, including anaphylaxis, have been reported; if hypersensitivity occurs, discontinue and institute supportive treatment measures.
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.
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Teratogenic effects were not observed in animal studies; however, the manufacturer does not recommend use of arginine during pregnancy.
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.
Oral: Well absorbed
Vd: ~33 L/kg following a 30 g IV dose
Extensively metabolized in the liver and intestines (Cynober 2011)
Urine (16% during the first 90 minutes; biphasic elimination) (Tangphao 1999)
Serum: Oral: ~2 hours; IV: 22 to 30 minutes (Bode-Boger 1998; Tangphao 1999)
42 ‚ ± 2 minutes following a 30 g IV dose; exhibits nonlinear, dose-dependent elimination (Tangphao 1999)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, flushing, vomiting, or nausea. Have patient report immediately to prescriber severe injection site pain, redness, burning, or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.