Neurology -- Correspondence for Milligan et al., 71 (9) 665-669

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Correspondence published:

Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery: Nitin K. Sethi (21 November 2008)

Reply from the authors: Tracey A. Milligan, Shelley Hurwitz and Edward B. Bromfield (21 November 2008)

Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery 21 November 2008

Nitin K. Sethi,
New York-Presbyterian Hospital Weill Cornell Medical Center
525 East 68th Street New York, NY 10065
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Re: Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery

sethinitinmd{at}hotmail.com Nitin K. Sethi

I read with interest the article by Milligan et al. comparing the efficacy and tolerability of levetiracetam to phenytoin after supratentorial neurosurgery. [1] The authors provide valuable information regarding the efficacy of levetiracetam in preventing peri-operative seizures.
Phenytoin is rarely, if ever, dosed according to body weight. In general, patients are given a gram and then put on maintenance (300mg/day). Initially, this results in sub-therapeutic serum levels making patients prone to peri-operative seizures.
One potential advantage of phenytoin over levetiracetam is that serum levels are standardized and can be readily checked. Rapid dose adjustments are possible in the setting of a break-through seizure while on phenytoin. In most centers, this is not possible with levetiracetam which leads to physicians “blindly” increasing the maintenance dose.
This problem should be considered before levetiracetam replaces phenytoin as the drug of choice for seizure prophylaxis after supratentorial neurosurgery.
References
1. Milligan TA, Hurwitz S, Bromfield EB. Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Neurology 2008;71:665-669.
Disclosure: The authors report no disclosures.

Reply from the authors 21 November 2008

Tracey A. Milligan,
Brigham and Women's Hospital, Harvard Medical School
75 Francis St, Boston, MA 02115,
Shelley Hurwitz and Edward B. Bromfield
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Re: Reply from the authors

tmilligan{at}partners.org Tracey A. Milligan, et al.

We thank Dr. Sethi for his comments. We agree that phenytoin is rarely dosed according to body weight with respect to perioperative prophylaxis and that this practice may result in sub-therapeutic phenytoin levels. Furthermore, phenytoin may not be given a fair chance to show its full potential in seizure prophylaxis.
However, the incidence of seizures was lower (4%) than the incidence of adverse drug reactions (ADRs) (18%) in the patients receiving phenytoin. In addition, most of our patients had levels within the usual therapeutic range although at the lower end. Targeting higher levels is unlikely to mitigate this problem and may lead to an increase in ADRs.
The potential difficulty in obtaining levetiractetam levels is not a clear drawback to its use as prophylaxis in the perioperative period. In this study, we most commonly used a dose of 500 mg levetiractetam twice daily. This dose has been effective in preventing seizures in other clinical situations and most studies have not shown a clear dose-response relationship across individuals.
In addition, levetiracetam is pharmacokinetically more predictable than phenytoin so that there is a reduced need to monitor levels. If a breakthrough seizure does occur while the patient is receiving levetiractetam, the decision to increase the dose is usually made without obtaining a level. This occurs in various clinical situations.
We do not think this is a decision made “blindly,” but rather one made with consideration of the patient, drug, dosage, and other clinical factors.
Disclosures: This study was funded by a UCB young investigator's award. T.A.M. and E.B.B. have received honoraria and/or consulting fees totaling less than $10,000 from UCB.