FDA Drug Safety Podcasts – Colistimethate

On June 28, 2007 the FDA issued a public health advisory for colistimethate also known and marketed as Coly-Mycin M.  Colistimethate is used to treat infections caused by certain types of bacteria.  A patient died after a pharmacy mixed colistimethate into a liquid for inhalation via a nebulizer.  When colistimethate is mixed into a liquid form, the product begins to break down into other chemicals that can damage lung tissue.  The FDA advised that if colistimethate is mixed into liquid form it should be used promptly by the patient.  Colistimethate is FDA approved only for injection into a vein or muscle.1

Colistimethate is the sulfamethyl derivative of colistin and is inactive until it is hydrolyzed in the body to colistin.  In treating patients with cystic fibrosis, colistimethate is often mixed with sterile water and a buffer to form a solution just prior to inhalation via a nebulizer.  Colistimethate spontaneously hydrolyzes to the active form, colistin, after mixing with water, and one of the components of colistin, polymyxin E1, is toxic to lung tissue.  Pre-mixing colistimethate into solution and storing it for longer than 24 hours results in increased concentrations of colistin in solution, increasing the potential for lung toxicity.2

Colistimethate is indicated for Acinetobactor species, Bordetella species, Citrobacter species, Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella species, Shigella species, and Vibrio species.  Colistin works by binding to gram-negative bacterial cell membrane phospholipids, increasing the permeability of the cell membrane resulting in loss of metabolites essential to bacterial existence.  The normal dosage of colistimethate is 2.5 to 5 mg/kg IM or IV per day in two to four divided doses.  The dosage reported for nebulizer inhalation is 150mg via nebulization twice daily.2

References:

1. www.fda.gov/cder/drug/podcast/colistimethate_full.htm
2. clinical pharmacology online

Prepared by Jeremy Westfall, Pharm.D. Candidate