University of Florida College of Medicine, Gainesville, FL
Correspondence to: Paul B. Langevin, MD, Department of Anesthesiology, PO Box 100254, Gainesville, FL 36210-0254; e-mail: firstname.lastname@example.org
To the Editor:
In 1986, the Food and Drug Administration (FDA) issued a warning
stating that drugs that contain sulfites were hazardous and should be
withdrawn whenever alternative formulations were
available.1 Since this warning, there has been an effort
within the pharmaceutical industry to avoid the addition of sulfites to
virtually all compounds when possible. Indeed, only two drugs commonly
used by anesthesiologists still contain sulfite: curare and the generic
form of propofol, which was recently approved by the FDA despite its
decade-old admonition to avoid this agent.1
The incidence of sulfite allergy is estimated at > 1 in 1,000
patients.2The manifestations of sulfite allergy range
from a mild dermatitis, to bronchospasm, to outright
anaphylaxis.3The exact toxicity of the additive is
unknown in humans, although chronic exposure can result in renal
failure.4The median lethal dose (LD50) of
sodium metabisulfite in rats is < 125 mg/kg.5
Given that generic propofol contains 0.25 mg/mL sodium metabisulfite
(see package insert for generic propofol [Gensia; Irvine,
CA]), infusion at a rate of only 50 μg/kg/min will result in sulfite
administration approaching toxic levels (ie, near the
LD50 for rats) in about 24 h. More important, children
frequently exhibit toxicity to many compounds at lower concentrations
than adults, but typically they require higher doses of propofol to
achieve the desired effect. Therefore, the addition of sulfites to this
drug is particularly worrisome for the potential effects in the
Clinicians are likely to simply substitute the generic propofol for
Diprivan (Zeneca Pharmaceuticals; Wilmington, DE) because the FDA gave
the generic drug AB status, which for many physicians implies an
equally safe preparation. Indeed, there is no evidence to indicate that
generic propofol is harmful or likely to cause an adverse event.
Unfortunately, there is also no evidence to the contrary. Well-designed
laboratory and clinical studies are needed to determine its harmful
effects. Unfortunately, the clinical studies may require large
numbers of patients, which makes laboratory data even more critical
when a drug is being used prior clinical to testing. Until such data
become available, clinicians may wish to use generic propofol only in
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