Fosphenytoin | clinical impact review evidence specifically comparing fosphenytoin with phenytoin in patients with SE so any extrapolation of results conducted in other patient groups must therefore be treated with caution. Since fosphenytoin and phenytoin are bioequivalent and therefore of equivalent efficacy, it is unlikely that there will be any difference in patient outcome costs in terms of the proportion achieving seizure reduction. Therefore, differences in drug-related patient outcome costs of SE treatment are likely to include the failure of the patient to respond to the treatment, the period spent in the ED (time to discharge), and the management of drug-related adverse events. As fosphenytoin can be administered more rapidly, and it is at least as well tolerated as phenytoin, cost differences with these latter outcomes may, in theory, favour fosphenytoin. Four pharmacoeconomic analyses comparing intravenous fosphenytoin with intravenous phenytoin in the ED setting have been conducted in the USA (Table 7). The study by Marchetti et al. suggested a cost saving of $US386.89 with fosphenytoin relative to phenytoin (Marchetti et al. 1996). However, this study used clinical results from a multicenter trial conducted in one state and financial data from a different institution in California, which would probably differ with both other states and other countries. In addition, calculation of the cost of emergency room treatment relied upon average fixed and variable costs, whereas only variable or marginal care costs are recommended for this type of analysis (Weinstein et al. 1996). However, more pertinent to this review, patients with SE were actually excluded from the analysis. In the analysis performed by Rudis et al. (2004), the most cost- effective loading method in most settings was phenytoin administered orally. The time taken to achieve therapeutic blood levels with this route of administration precludes its use as a treatment for SE. A more relevant comparison in this study showed that the incremental cost-effectiveness ratio (i.e. the difference in costs divided by the difference in health outcomes) was $US387.27/h of ED time saved for intravenous fosphenytoin versus intravenous phenytoin (Table 7) (Rudis et al. 2004). In this study, drug administration was carried out at a General Clinical Research Center under conditions which do not accurately represent acute treatment. In addition, SE patients were excluded (Swadron et al. 2004). A study using cost-minimization analysis (i.e. the costs of two methods producing the same outcome) by Touchette and Rhoney (2000) showed that phenytoin was the preferred option in 97.3% of occasions: expected total treatment costs $US5.39 vs 110.14 with fosphenytoin (Table 7). However, one-way sensitivity analysis demonstrated that the frequency and cost of treating an episode of purple glove syndrome could possibly affect the decision. A two-way sensitivity analysis was conducted with the cost and frequency of purple glove syndrome as variables. For fosphenytoin to be the preferred option the rate of purple glove syndrome with phenytoin had to exceed 1% and/or the cost of managing this adverse event had to exceed $US10 000/episode (Touchette & Rhoney 2000). The base case analysis was derived from a study that used reduced rates of administration of phenytoin and fosphenytoin, which biased the magnitude of the difference in adverse events seen with the intravenous administration rates of the two drugs (Coplin et al. 2002). The rate of purple glove syndrome with phenytoin treatment in this study is therefore likely to be lower than expected. O’Brien et al. reported an incidence of purple glove syndrome with phenytoin of up to 5.9% (O’Brien et al. 1998). Thus it may be that fosphenytoin could be more cost- effective when a higher incidence of adverse events, such as purple glove syndrome, with phenytoin is taken into account. Table 7 | Summary of economic studies involving intravenous fosphenytoin Level of evidence Analysis and outcome Cost-minimization analysis from an RCT Total treatment cost for base case of $US5.39 for PT vs. $US110.14 for FOS. PT was the preferred option for 97.3% of patients Comparators Study population FOS (iv) vs PT (iv) Base case from a randomized trial (n=77 PT; n=202 FOS) Study reference Touchette & Rhoney 2000; Coplin et al. 2002 Rudis et al. 2004; Swadron et al. 2004 Marchetti et al. 1996 © 2005 Core Medical Publishing Limited 2 2 2 2 72 AE, adverse effect; ED, emergency department; FOS, fosphenytoin; iv, intravenous; PT, phenytoin; RCT, randomized clinical trial. Cost-effectiveness based on rates of AE and time to safe discharge from FOS (iv) vs PT (iv) ED from an RCT Treatment cost per patient was $US2.83, 21.16, and 175.19 for oral PT, iv PT, and iv FOS, respectively Cost-effectiveness ratios were $US3.90/h of ED time saved for oral PT vs iv PT and $US387.27/h of ED time saved for iv FOS vs iv PT Outcomes and costs from an RCT. (n=16 oral PT; n=14 iv PT; n=15 iv FOS) Drug acquisition cost and estimated cost to manage AEs within the ED Total ED drug-related AE costs per patient were $US536.86 for PT compared with $US66.68 for FOS. Subtracting drug acquisition costs results in a net saving of $US386.89 with FOS Cost estimation and cost-effectiveness For loading doses average cost-effectiveness ratio of iv PT alone ($US225) was higher than iv FOS ($US130) Incremental cost-effectiveness ratio was $US97 to replace PT loading doses with FOS FOS (iv) vs PT (iv) Not SE patients, n=39 FOS; n=13 PT FOS (iv) vs PT (iv) Study based on questionnaire given to Armstrong et nurses to determine incidence and al. 1999 outcomes with AEs with PT and FOS