An amino acid called arginine encourages the production of prolactin from the hypothalamus and growth hormone from the pituitary gland.

The following conditions are indicated for its use during treatment

• As a diagnostic aid:

  • It can be administered intravenously to patients whose pituitary reserve for human growth hormone can be measured to aid in diagnosis by stimulating the release of the hormone. 

  • As a diagnostic tool, it is also used to rule out diseases such gigantism, acromegaly, panhypopituitarism, chromophobe adenoma, pituitary dwarfism, postsurgical craniopharyngioma, hypophysectomy, and pituitary trauma.

• Off Label Use of Arginine in Adults:

  • Acute hyperammonemia linked with urea cycle disorders

  • Chronic therapy in Urea cycle disorders.

Arginine Dose in Adults

Dose in the treatment of Diagnostic aid to assess the pituitary function (Growth hormone stimulation test).

• 30 gms intravenously as a STAT dose

Dose in the treatment of acute Hyperammonemia (urea cycle disorders and off-label):

Note: Arginine hydrochloride product and a particular enzyme deficiency are the key factors that influence dosage.

• The course of therapy should be followed until the ammonia levels are normal.
• If a loading dose has been administered, it shouldn't be given again.
• If the patient develops hypotension and an enzyme deficit is found, the dose of arginine can be decreased.
• Administer dialysis together with sodium phenylacetate and sodium benzoate concurrently.

• Deficiency of Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL):
  • Loading dose:
    • It is administered intravenously in doses of 600 mg/kg, followed by daily continuous intravenous infusions of  600 mg/kg.
• Deficiency of Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or Nacetylglutamate synthetase (NAGS):
  • Loading dose:
    • It is administered intravenously in doses of 200 mg/kg, followed by a daily infusion of 200 mg/kg.
• Unconfirmed or pending diagnosis:
  • Loading dose:
    • Initial intravenous administration of 600 mg/kg, followed by a daily intravenous infusion of 600 mg/kg.
    • Reduce the dose to 200 mg/kg/day if the diagnostic possibilities of ASS and ASL are ruled out.

BSA-directed dosing:

• Deficiency of Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL):
  • Loading dose:
    • 12 g/m intravenously, followed by a daily infusion of 12 g/m2 of medication continuously.
• Deficiency of Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC):
  • Loading dose:
    • 4 g/m2 intravenous, followed by a daily infusion of 4 g/m2 continuously

Dose in the treatment of chronic therapy of Urea cycle disorders (off-label):

Note: Dosing based on arginine-free base powder product:

• Argininosuccinate synthetase (ASS, Citrullinemia) or Argininosuccinate lyase (ASL) deficiency:
  • It is given as 0.4 -0.7 g/kg/day or 8.8 to 15.4 g/m²/day orally in 3 to 4 divided doses.
• Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC) deficiency:
  • It can be given according to 2.5 to 6 g/m² /day in orally 3 or 4 divided doses (maximum dose is 6 gms/day) has been recommended, but, citrulline may be preferred therapy.

Arginine Dose in Childrens

Dose in the treatment of Pituitary function test:

Note: Doses in accordancce with arginine hydrochloride product:

• Infants, Children, and Adolescents:
  • 0.5 gm/kg is administered intravenously over 30 minutes to a maximum dose of 30 gms dose

Dose in the treatment of Metabolic alkalosis: 

• Infants, Children, and Adults:

Note: Arginine hydrochloride may be used as an alternative treatment for the treatment of uncompensated metabolic alkalosis after NaCl and KCl supplementation have been optimized.

• It shouldn't be used as the first step in a treatment plan for chloride supplementation.
• 4.75 mEq of chloride are present in 1 g of arginine hydrochloride

Note: Dose is set according to arginine hydrochloride product.

• Arginine hydrochloride dose in mEq equals 0.5 kg times [HCO3 - 24] of body weight.

• Where HCO3 is the patient's serum bicarbonate level in milliequivalents per litre.

• Correcting hypochloremia:
  • the patient's serum chloride content in mEq/L, where Cl is the dose of arginine hydrochloride in mEq, and weight in  kg times [103 - Cl].

Dose for treating acute Hyperammonemia with urea cycle disorders in patients: 

• Infants, Children, and Adults:

Note: It is given together with sodium phenylacetate and sodium benzoate. The dosage is determined on the particular enzyme deficiency.

• Until ammonia levels are within the normal range, treatment should be administered.
• The loading dose may be decreased or eliminated if the patient is currently receiving arginine treatment.
• A loading dose shouldn't be administered once it has been utilised.

Note: Arginine hydrochloride product-based dosing.

• Weight-directed doses:
  • Deficiency of Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia):
• The loading dose is administered intravenously at 600 mg/kg.
• Then an intravenous infusion lasting 600 mg/kg/day is started continuously.

Deficiency of Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or Nacetylglutamate synthetase (NAGS):

• An intravenous loading dosage of 200 mg/kg
• 200 mg/kg/day of an intravenous infusion were then administered continuously.
• Diagnosis Unconfirmed or pending:
  • An intravenous loading dosage of 600 mg/kg
  • A continuous intravenous infusion of 600 mg/kg/day is then administered.
  • The dose may be decreased to 200 mg/kg/day if ASS and ASL are ruled out as diagnostic options.
• BSA-directed dosing:
  • Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia) deficiency:
    • An intravenous loading dose of 12 g/m2 is administered.
    • Then a continuous intravenous infusion lasting 24 hours at 12 g/m2
  • Disorder of Carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC):
    • An intravenous loading dosage of 4 g/m2
    • Followed by a daily infusion of 4 g/m2 of an ongoing intravenous solution.

Dose in the treatment of chronic therapy of Urea cycle disorders: 

• Infants, Children, and Adults:

Note: Depending on the patient's reaction, the dose should be customised. As part of a sick-day pattern, doses could be increased by 50%

Deficiency of Argininosuccinic acid lyase (ASL) or argininosuccinic acid synthetase (ASS, citrullinemia):

• Weight-directed dosing:
  • It is given as 400 to 700 mg/kg/day orally in 3 to 4 divided doses
• BSA-directed dosing:
  • It is given as 8.8 to 15.4 g/m/day orally in 3 to 4 divided doses

Carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC) or N-acetyl glutamate synthetase (NAGS) deficiency:

• Weight-directed dosing is 170 mg/kg/day orally in 3 to 4 divided doses
• BSA-directed dosing is 3.8 g/m /day orally in 3 to 4 divided doses

Pregnancy Risk factor: B

• Animal studies have not shown any teratogenic effects.
• The manufacturer doesn't recommend arginine use during pregnancy.

Arginine use during breastfeeding:

• Although amino acids are part of breastmilk, their amount after arginine administration remains unknown.

Arginine Dose in Renal Disease:

The manufacturer has not recommended any dose adjustments in patients with renal disease, however, it should be used with caution.

Arginine Dose in Liver Disease:

Although the manufacturer has not advised any dose modifications in people with liver disease, it should nevertheless be used cautiously.

Less Common Side Effects of Arginine Include:

• Cardiovascular:
  • Venous irritation
  • Flushing (with rapid Intravenous infusion)
• Central nervous system:
  • Numbness
  • Headache
• Gastrointestinal:
  • Vomiting
  • Nausea

Contraindication to Arginine Include:

Allergies to arginine and any other ingredients in the formulation

Warnings and Precautions

• Extravasation:
  • It has vesicant-like properties and is an irritant.
  • Because of the hypertonicity in the Intravenous solution it is best to administer intravenous infusions only using a patent catheter that has been placed within a patent vein.
  • Extravasation can cause skin necrosis and burn-like reactions. This may require surgical intervention.
  • Local irritation may occur if you infuse too often (eg, more than 30 minutes).
• Hypersensitivity reactions
  • Reports of severe reactions, including anaphylaxis and other allergic reactions have been made.
  • If hypersensitivity develops, stop using the medication and seek out supportive treatment.
• Reactions that are related to infusion:
  • Flushing, nausea, and vomiting may occur if the infusion rate is too low (eg, for less than 30 minutes).
• Electrolyte imbalance:
  • Patients with an electrolyte imbalance should be cautious because of the high chloride content.
• Renal impairment
  • Excreting nitrogen-containing products is a result of arginine metabolism.
  • Patients with impaired renal function should be cautious about using it as decreased excretion could lead to an increase in the burden of nitrogen or amino acids.

Monitor:

• Acid-base status (arterial or capillary blood gases),
• Serum electrolytes (sodium, potassium, chloride, bicarbonate, phosphorous),
• BUN,
• Plasma glucose,
• Plasma amino acids,
• Ammonia,
• Blood pressure (patients with hyperammonemia due to a disorder of the urea cycle).
• Monitor infusion site.

How to administer Aginine?

Intravenous:

• It is given undiluted over a 30-minute period.
• The manufacturer advises transferring the medication to a different container before administration for doses less than 30 gms (300 mL).
• Due to the pituitary gland's reduced reaction, extending the infusion period may render the test invalid.
• Patients with urea cycle abnormalities should get a loading dosage over 90 to 120 minutes in order to address their hyperammonemia.
• The maintenance infusion's maximum dose per kilogramme per hour is 150 mg.
• It has vesicant-like irritation characteristics.
• To prevent extravasation, the catheter or intravenous line needs to be appropriately positioned both before and during the infusion.
• Some professionals advise use a central catheter for all infusions.

Management of extravasation of the Arginine:

Extravasation should be carefully aspirated after the infusion is stopped right away (leave the needle or cannula in place).

DO NOT FLUSH THE LINE.

• Start the hyaluronidase antidote medication. 
• Use a 25-gauge needle to inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL intradermal or subQ injections  into the region of extravasation at the leading edge. 
• The catheter that generated the infiltration may also be used to inject hyaluronidase.
• Take out the cannula or needle
• Use cold, dry compresses.
• Raising the extremity

Oral Arginine free base:

• Administer it with meals in equally divided doses.
• Oral formulations are often marketed as dietary supplements.
• The National Urea Cycle Disorders Foundation advises against taking arginine HCl as an oral dietary supplement.

Mechanism of action of Arginine:

• Prolactin and growth hormone are released from the hypothalamus and pituitary, respectively, as a result of stimulation.
• Patients with impaired pituitary function are unable to respond to the stimulatory effects of arginine.
• Patients with urea-cycle disorders are unable to form arginine.
• Therefore, exogenous administration is necessary.

Oral arginine can be taken wellabsorbedAndMetabolizedIt is found in the liver and intestines. It is abioavailabilityAfter 30 gms intravenous infusion, the half-life elimination was 42+/- 2 minutes. Time to get therepeak serum concentrationAfter oral administration, it takes approximately 2 hours. After intravenous injection, it takes 22-30 minutes. It isexcretedIn the urine.

Arginine international brands:

• Arginina
• Rocmaline

Arginine brands in Pakistan: