The (Phosphate) Salt and Pepper of Common EM Medications
Drug delivery has always been a fascinating subject for me. Some of us may take for granted the countless hours dedicated toward the research, design, and development of new drugs and delivery systems in order to optimize the ability for a drug is able to reach its site of action; essentially, to make sure that the drug that we think will work will actually “do its thing.”
What is this adverse effect that I am alluding to? Believe it or not, it is perineal pruritus.While several case reports and controlled studies have been published regarding this adverse effect, unfortunately, the mechanism is not clearly understood. However, it is thought to be due to the phosphate group on these compounds, and commonly occurs as the drug is given as a rapid intravenous (IV) push. This same adverse effect was also demonstrated with rapid IV infusion of the agent fospropofol (which, as a side note, interestingly enough, has been discontinued from the US market since June 2012). The effect and any pain associated with perineal pruritus subsides as hydrolysis of the prodrug to the parent compound occurs, and there are generally no long-term consequences of the effect for the patient (other than the lasting memory of experiencing such an unpleasant reaction).
The potential of this adverse effect associated with these phosphate salts can be minimized in one of two ways. Both fosphenytoin and dexamethasone sodium phosphate can be administered as an intramuscular injection as an alternative route of administration. If IV access is obtained and necessary, dexamethasone can be mixed in 50 mL of diluent and given as an IV piggyback over five to ten minutes. In the case of fosphenytoin, we know that the rate of administration should not exceed 150 mg/min, and so this rate should be taken into account when administering the drug to a patient via the IV route.
Although much effort is exercised to ensure adequate delivery of a drug through the body, regardless of how well-intentioned efforts may be, the potential consequences can certainly be unanticipated and may go unrecognized as being associated with the drug delivery system of the compound. As the saying goes, “With great power…comes great responsibility.”
Huttunen KM, Raunio H, Rautio J. Prodrugs: from serendipity to rational design. Pharmacol Rev 2011; 63:750-771.
Perron G, Dolbec P, Germain J, et al. Perineal pruritus after IV dexamethasone administration. Can J Anaesth 2003; 50:749-750.
Singh M, Sharma CS, Rautela RS, et al. Intravenous dexamethasone causes perineal pain and pruritis. J Anesthe Clin Res 2011; S1:001.
Eldon MA, Loewan GR, Voightman RE, et al. Pharmacokinetics and tolerance of fosphenytoin and phenytoin administration intravenously to healthy subjects. Can J Neuro Sci 1993; 20:S810.
Pruitt RE, Cohen LB, Gibiansky E, et al. A randomized, open-label, multicenter, dose-ranging study of sedation with Aquavan injection (GPI 15715) during colonoscopy. Gastrointest Endosc 2005; 61:AB111.
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