Cost-effectiveness analysis of intravenous levetiracetam versus intravenous phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury

ClinicoEconomics and Outcomes Research Dovepress open access to scientific and medical research o R i g i n al re s earc h ClinicoEconomics and Outcomes Research downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Cost-effectiveness analysis of intravenous levetiracetam versus intravenous phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury Rashid Kazerooni 1 Mark Bounthavong 1,2 1 Pharmacoeconomics/Formulary Management, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; 2UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA This article was published in the following Dove Press journal: ClinicoEconomics and Outcomes Research 5 March 2010 Number of times this article has been viewed Objective: There has been growing interest in newer anti-epileptic drugs (AEDs) for seizure prophylaxis in the intensive care setting because of safety and monitoring issues associated with conventional AEDs like phenytoin. This analysis assessed the cost-effectiveness of levetiracetam versus phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury (TBI). Methods: A cost-effectiveness analysis was conducted from the US hospital perspective using a decision analysis model. Probabilities of the model were taken from three studies comparing levetiracetam and phenytoin in post neurosurgery or TBI patients. The outcome measure was successful seizure prophylaxis regimen (SSPR) within 7 days, which was defined as patients who did not seize or require discontinuation of the AED due to adverse drug reactions (ADRs). One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test robustness of the base-case results. Results: The total direct costs for seizure prophylaxis were $8,784.63 and $8,743.78 for levetiracetam and phenytoin, respectively. The cost-effectiveness ratio of levetiracetam was $10,044.91 per SSPR compared to $11,525.63 per SSPR with phenytoin. The effectiveness probability (patients with no seizures and no ADR requiring change in therapy) was higher in the levetiracetam group (87.5%) versus the phenytoin group (75.9%). The incremental cost effectiveness ratio for levetiracetam versus phenytoin was $360.82 per additional SSPR gained. Conclusions: Levetiracetam has the potential to be more cost-effective than phenytoin for early onset seizure prophylaxis after neurosurgery if the payer’s willingness-to-pay is greater than $360.82 per additional SSPR gained. Keywords: phenytoin, levetiracetam, seizure prophylaxis, cost-effectiveness, traumatic brain injury (TBI), and neurosurgery Introduction Correspondence: Mark Bounthavong Pharmacoeconomics Clinical Specialist, Veterans Affairs San Diego Healthcare System, Assistant Clinical Professor, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, 3350 La Jolla Village Drive (119), San Diego, CA 92161, USA Tel +1 858-552-8585 ext. 3158 Fax +1 858-642-1499 Email submit your manuscript | www.dovepress.com Dovepress Powered by TCPDF (www.tcpdf.org) Patient who undergo neurosurgery are at increased risk of early postoperative seizure events.1,2 An estimated 20% to 50% of patients have at least one postoperative seizure, depending on the type of surgery.3,4 Early postoperative seizures, which are seizures that occur within 1 week of surgery, occur in 15% to 20% of neurosurgery patients.3–5 Patients who sustain traumatic brain injury (TBI) are also at increased risk, with about 6% to 10% of patients suffering early onset seizures.6,7 Incidence can be as high as 30% in certain groups, such as those with more severe head trauma, subdural hematomas, or penetrating head injuries.6–8 Seizure prophylaxis with antiepileptics ClinicoEconomics and Outcomes Research 2010:2 15–23 15 © 2010 Kazerooni and Bounthavong, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress ClinicoEconomics and Outcomes Research downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Kazerooni and Bounthavong has shown promise in reducing early onset seizures in both patient groups.2,9–11 However, there is no commonly accepted treatment algorithm to provide guidance as to which antiepileptic drug (AED) should be preferred which has led to a variety of clinical practices.12 Phenytoin is the most common AED used after neurosurgery and TBI for seizure prophylaxis.9–11,13 In a metaanalysis that pooled early onset seizure events from five post neurosurgery trials, phenytoin was associated with decreased seizure risk in the first week by 44% (relative risk, RR: 0.56, 95% confidence interval [CI]: 0.38–0.84) compared to control.13 Additionally, a review that pooled the two class I (randomized placebo controlled) studies investigating phenytoin prophylaxis after TBI showed a 63% reduction in seizures (RR: 0.37, 95% CI: 0.18–0.74).9 Despite evidence that supports phenytoin use in early seizure prophylaxis, there are a number of issues that limit its use. Phenytoin requires constant laboratory monitoring which is a burden to the patient as well as time consuming for hospital staff.14 Moreover, due to phenytoin’s zero-order (Michaelis-Menten) pharmacokinetics which result in a non-linear relationship between dose and subsequent serum levels, a small change in dose can result in a disproportionate increase in serum concentration.15 Furthermore, rare and potentially fatal skin reactions have been reported with phenytoin, such as Stevens Johnson syndrome and purple glove syndrome.16 Finally, phenytoin can act as a substrate or inducer of several of the cytochrome P450 enzyme which can potentially lead to drug interactions that may consequently require dose adjustments or discontinuation of medications.14 Due to these known problems with phenytoin for early seizure prophylaxis after neurosurgery, there has been an interest in using alternative AEDs for this indication. Other medications that have been evaluated for early onset seizure prophylaxis include carbamazepine, valproate, phenobarbital, and levetiracetam.9,17 Shaw et al evaluated cabamazepine (CBZ) against a no treatment historical cohort after neurosurgery and reported a 39% reduction in seizure events (RR: 0.61, 95% CI: 0.29–1.29).4 Early onset seizure incidence was 11% in the CBZ group (n = 106) and 19% in the no treatment historical cohort (n = 59).4 Glötzner et al in a prospective placebo-control study, assessed CBZ after TBI and reported a 63% reduction in early seizure events (RR: 0.37, 95% CI: 0.18–0.78).18 Seizure incidence was 10.7% in the CBZ group (n = 75) and 28.9% (n = 76) in the placebo group.18 Holland et al, in a randomized double-blind study, evaluated valproate for seizure prophylaxis after craniotomy and reported a no (...truncated)