Multidose vials, parenteral preservation

A parenteral product in a multidose vial must contain a preservative to protect the contents of the vial against contamination during repeated withdrawal of dose aliquots. 

Another important component of most vaccine formulations is a suitable preservative. The three most commonly used preservatives in available vaccines are phenol, 2-phenoxyethanol, and ethyl mercurithiosalicylate (thimerosal). Thimerosal, in particular, is used in multidose vials as an antimicrobial preservative. Concerns about the presence of mercury in thimerosal (25 pg/dose) has led to FDA stopping the use of this preservative in all vaccines by an amendment to the FDA Modernization Act of 1997. By 2001, thimerosal was removed from most childhood vaccines as a precautionary measure. The sources of all of the preservatives for vaccines are the same suppliers that supply preservatives for the parenteral dosage forms (J. T. Baker, Aldrich, Spectrum, etc. from U.S.A.). Table 2 lists some of the preservative concentrations in common vaccines. 

Benzyl alcohol is a preservative that may be present in multidose vials of bacteriostatic sodium chloride and bacteriostatic water for injection and pharmaceuticals available in multidose vials for parenteral use. An association between the presence of benzyl alcohol in solutions used for flushing intravascular catheters and to reconstitute medications and a gasping syndrome and deaths in neonates was first reported in the early 1980s.The neonates also displayed clinical findings such as an elevated anion gap, metabolic acidosis, CNS depression, seizures, respiratory failure, renal and hepatic failures, cardiovascular collapse, and death. Those at highest risk were premature infants who weighted less... 

A. Parenteral. Labetalol hydrochloride (Normodyne, Trandate), 5 mg/mL, 20-mL ampules, 40- and 60-mL multidose vials (with EDTA and parabens as preservative). 

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