Safety Alert – Arginine (Updated 7/16/2009)

LWPES Members:

A recently released report from The Food and Drug Administration (FDA) highlights the potential for serious adverse events associated with arginine infusions ³.  These include death, as occurred in a three year-old boy who received an accidental overdose of arginine-HCL in a growth hormone stimulation test² From 1973-2008, a total of 50 cases of complications including 4 deaths from L-arginine overdose were reported. Of note, the overdoses occurred in children three years of age or less who received 3-10 times the indicated dose.  Adverse events  included systemic abnormalities such as metabolic acidosis and respiratory distress, as well as hypersensitivity reactions, injection site reactions after extravasation, cerebral edema, headache and intractable vomiting. At least one of the extravasation episodes required skin grafting.  Hematuria, which  is not listed as a side effect in the product labeling, was also noted in 6 cases.  

The recommended dose of arginine-HCL is 0.5 gms*/kg intravenously with a maximum dose of 30 gms* when used for growth hormone stimulation testing. When given appropriately , this test is known to be safe and with minimal side effects.  In view of its potential toxicity, it is critical that dispensing pharmacies and administering nurses be educated regarding the dangers of arginine overdose and  that standardized procedures to prevent such incidents be implemented.  As a major prescriber of arginine, pediatric endocrinologists also have a duty to report adverse effects to the FDA.  These data help physicians accurately assess and discuss the risks and benefits of arginine administration with patients and their families

For more information, please refer to the FDA Drug Safety Newsletter at

http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/default.htm

To voluntarily report a suspected adverse drug reaction go to: 

https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm       

¹www.cbsnews.com/stories/2008/.../main3921119.shtml

² Silverstein JH, Malasanos TH, Valladares, A.  Arginine overdose:  Death in a child:  case report.  Reactions Weekly. (1205):8, June 7, 2008.

³ http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/default.htm

* The Arginine Safety Alert dated 7/10/09 had originally listed the doses of Arginine as mg/kg when they should be grams/kg body weight, i.e. Arginine-HCl 0.5 gm/kg intravenously with a maximum dose of 30 gms.