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Precipitation of Diazepam From Intravenous Preparations

William J. Jusko, PhD; Mark Gretch; Robert Gassett, MS
JAMA. 1973;225(2):176. doi:10.1001/jama.1973.03220290054019.
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To the Editor.—  The recent article by Langdon et al in The Journal (223:184, 1973) described the 3.5% incidence of thrombophlebitis that occurs when diazepam (Valium) is given intravenously. Precipitation of the relatively water-insoluble diazepam may account for this problem.Studies of the precipitation of diazepam were prompted by our observation that this product was frequently administered by injection through the tubing of an intravenous infusion set, rather than directly into the patient. This is contrary to the warning of the manufacturer who stated in the package insert that: "When used intravenously the solution should be injected slowly, directly into the vein, taking at least one minute for each 5 mg (1 ml) given. Do not add to I.V. fluids." The limited aqueous solubility of diazepam necessitates its formulation into a solution containing propylene glycol (40%) and alcohol (10%), buffered with benzoate sodium and benzoic acid (5%), and preserved with benzyl


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