Tolerability complements efficacy
“Most treatments with high Success Rates also had more negative Summary
Complaint Scores except for LEV [Keppra] that had both high efficacy
and very low adverse effect rates”
(Cramer JA, Ben-Menachem E, French J. Epilepsy Research 2001; 47: 17-25. 24 col 1)
Incidence of Most Common Adverse Events in Phase
III Trials
Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy.
An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.
Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy.
Piazzini A et al., Epilepsy Res. 2006 Mar;68(3):181-8. Epub 2005 Dec 5.
A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials.
Cramer JA et al., Epilepsy Behav. 2003 Apr;4(2):124-32.
(Cramer JA, Ben-Menachem E, French J. Epilepsy Research 2001; 47: 17-25. 24 col 1)
Well tolerated
- 4 placebo-controlled studies
(3 efficacy1,2,3, 1 safety4)
- 1023 patients aged 14 -70 years
- add-on treatment for partial seizures
- 12 - 14 weeks evaluation periods
- 1000 - 3000 mg/day1,2,3, up to 4000 mg in the safety study 4
Incidence of Most Common Adverse Events in Phase
III Trials
All with concomitant AEDS.
* Most were common colds and upper respiratory tract infections.
Adapted from Shorvon and van Rijckevorsel, J Neurol
Neurosurg Psychiatry 2002;72:426-428
Erratum: Shorvon and van Rijckevorsel, J Neurol Neurosurg
Psychiatry 2002;73:102
Events leading to withdrawal or dose reduction
Adverse events > 1 %
Adapted from Harden, Epilepsia 2001;42(suppl.4):36-39
1 Shorvon et al., Epilepsia 2000;41(9):1179-1186
2 Cereghino et al., Neurology 2000;55:236-242
3 Ben-Menachem et al., Epilepsia 2000;41(10):1276-1283
4 Betts et al., Seizure 2000;9:80-87
5 Privitera et al., Eur. J. Neurol. 2002;9(suppl 2):177-178
2 Cereghino et al., Neurology 2000;55:236-242
3 Ben-Menachem et al., Epilepsia 2000;41(10):1276-1283
4 Betts et al., Seizure 2000;9:80-87
5 Privitera et al., Eur. J. Neurol. 2002;9(suppl 2):177-178
Low level of discontinuation
- In controlled clinical trials and during further open-label trials, 1422 patients were exposed to Keppra for a total of 2421 patient-years, with individual duration of exposure to Keppra of up to 8.1 years
- 15.8% of these patients had their therapy discontinued due to adverse events
- Most common adverse events leading to withdrawal from long-term treatment
(>1%) (n=1422) were somnolence 2%, convulsions 3.4%.
(Adapted from Krakow K, Walker M, Otoul C, et al. Neurology 2001;56:1772-1774. 1773 col 1)
No impairment of cognitive function
QOLIE-31 questionnaire revealed changes from baseline in cognitive function
- self evaluation of cognitive function showing canges in scores (n=246)
- Significantly higher self-evaluation of cognitive function vs placebo
Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy.
- Keppra was
well tolerated.
- The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam.
An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.
- Keppra was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.
Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy.
Piazzini A et al., Epilepsy Res. 2006 Mar;68(3):181-8. Epub 2005 Dec 5.
A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials.
Cramer JA et al., Epilepsy Behav. 2003 Apr;4(2):124-32.
