CLINICAL APPLICATION OF NEW GENERATION DRUG COMBINATIONS IN REFRACTORY EPILEPSY
Abstract number :
2.243
Submission category :
Year :
2003
Submission ID :
636
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Piotr P. Czapinski, Ewa M. Czapinska Epilepsy and Migraine Treatment Centre, Epilepsy and Migraine Treatment Centre, Cracow, Poland
Approximately 20-30% of patients treated for epilepsy require polytherapy due to unsuccessful monotherapy. Combinations of new generation anti-epileptic drugs are justified in resistance to classic drugs, combinations of classic and new generation drugs or when drug interactions have to be avoided. To-date, clinical information on combination of new generation agents are scarce and most commonly describe the addition of another drug to a first, ineffective agent.
In a 6-month follow-up, 197 two-drug combinations were assessed, using the pool of 5 new generation drugs: tiagabine (TGB), lamotrigine (LTG), vigabatrin (VGB), gabapentin (GBP) and topiramate (TPM). The exclusion criteria were refractory epilepsy with partial seizures, at least two seizures/month and therapeutic failure in treatment with either of two drugs forming a combination. At the time of a second drug addition, the patients were on the first drug monotherapy. The second agent was given at the minimal effective dose (MED.), i.e. TGB=30 mg, LTG=200 mg, VGB=2,000 mg, GBP=1,800 mg and TPM=200 mg. The measure of combination effectiveness was the percentage of responders (at least 50% seizure reduction), percentage of seizure-free patients and dose of drugs used in combination. Safety was measured by the percentage of patients excluded from the study due to unacceptable adverse effects.
The most effective combinations were GBP+LTG, TPM+GBP, VGB+LTG, VGB+TPM and TGB+GBP. The safest combinations were GBP+LTG, TGB+LTG, VGB+GBP, TGB+GPB and VGB+LTG. The following combinations were found to be of little safety: TGB+TPM, VGB+TPM and TGB+VGB. The most effective combinations required lower doses of individual drugs, which were slightly in excess of MED.
The most effective combinations include agents that best approximate the ideal from the pharmacokinetic viewpoint. The effect of these combinations requires low or medium doses. Combinations of drugs affecting the gabaergic system are of low safety and often are the cause of treatment termination, even when highly effective. [table1]