Actually, even single dose vials of depomedrol are not preservative free, although they are labeled that way. The FDA defines preservatives as agents to prevent bacterial/fungal growth and the list of approved preservatives for use in drugs in the US contains Benzalkonium chloride 0.02%, Benzethonium chloride 0.01%, Benzyl alcohol 0.75-5%, Chlorobutanol 0.25-0.5%, m-cresol 0.1-0.3%, Myristyl gamma-picolinium chloride 0.0195-0.169%, Paraben methyl 0.05-0.18%, Paraben propyl 0.01-0.1%, Phenol 0.2-0.5%,2-Phenoxyethanol0.50%, Phenyl mercuric nitrate 0.001%, and Thimerosal 0.003-0.01%. Depomedrol single dose contains Myristyl gamma-picolinium chloride, so even though the doses are low, contains a preservative.
Older formulations of depomedrol had a different formulation, and the case reports of arachnoiditis in the 70s, esp in Oz, may have been due to other preservatives or due to bacterial contamination, or due to contaminants in the PEG (some of the older forms of PEG had significant toxin impurities). In modern times, the incidence is much less with epidural administration, but it is not clear whether this is due to improved product or improved delivery accuracy. As for myristyl gamma picolinium chloride, there are no specific neurotoxcity studies I could find with the exception of rabbit retinal damage that occurs at twice or more the concentration of the chemical found in depomedrol. Most damage occurred only at 8 times the concentration in depomedrol. However, contact dermatitis and suppression of cartilage and synovial membrane glycosaminoglycan synthesis have also been demonstrated from this chemical. When given intraperitoneally and SC in rats in high concentrations, the drug is moderately toxic, but again these concentrations are orders of magnitude above that administered into the human epidural space.
