Summary of evidence and Expert Committee recommendations
An application was submitted for the addition of parenteral lorazepam 2 mg/ml; 4 mg/ml, for the intravenous treatment of prolonged convulsive seizures and status epilepticus in children and adults.
The Committee noted that the evidence presented in the application to support the superior effectiveness and safety of lorazepam compared to a range of other drug treatments for status epilepticus in adults and children
came from two Cochrane Reviews (1, 2) and five randomized comparative trials of parenteral lorazepam (3-7). Overall, the evidence showed that lorazepam was at least as effective as diazepam and had fewer
adverse effects when used for the management of status epilepticus.
The Committee recommended the inclusion of parenteral lorazepam with a square box to replace diazepam on the Model List based on its comparative effectiveness and safety with respect to other medicines for the management
of prolonged convulsive seizures and status epilepticus in adults and children. The rectal formulation of diazepam was maintained because it is a commercially available preparation and offers an option for treatment of
severe seizures in patients when intravenous access is not available.
1. Appleton R et al. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews, 2008, Issue 3. Art. No.: CD001905. DOI: 10.1002/14651858.CD001905.pub2.
2. Prasad K et al. Anticonvulsant therapy for status epilepticus. Cochrane Database of Systematic Reviews, 2005, Issue 4. Art. No.: CD003723. DOI: 10.1002/14651858. CD003723.
3. Treiman DM et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. New England Journal of Medicine, 1998,339:792–798.
4. Alldredge BK et al. A comparison of lorazepam, diazepam and placebo for the treatment of out-of-hospital status epilepticus. New England Journal of Medicine, 2001, 345:631–637.
5. Leppik IE et al. Double-blind study of lorazepam and diazepam in status epilepticus. Journal of the American Medical Association, 1983, 249:1452–1454.
6. McCormick EM et al. A prospective comparison of midazolam and lorazepam in the initial treatment of status epilepticus in the pediatric patient. Epilepsia, 1999, 40(suppl. 7):160.
7. Andermann F et al. A dose-response study of intravenous lorazepam in the treatment of status epilepticus. Epilepsia, 1994, 35(suppl. 8):10.