The new anticonvulsant drugs. Implications for avoidance of adverse effects.
Several new antiepileptic drugs offer a worthwhile alternative when standard antiepileptic drugs have failed. Suggestions have been made to improve the risk-benefit ratio of the new antiepileptic agents. More specifically, vigabatrin, which is a very useful and well tolerated new antiepileptic drug for refractory partial epilepsy, should be started at a low dosage of 0.5 g/day with increments of 0.5 g/day every week. Daily dosages exceeding 3 g/day should be restricted to patients with improvement. If necessary, the daily dosage of vigabatrin should be withdrawn slowly, i.e. by not more than 1 g/week. Lamotrigine is also a beneficial new drug for refractory partial and generalized seizures. However, the drug is associated with rash. In patients also receiving valproic acid (sodium valproate) [which inhibits the metabolism of lamotrigine], the incidence of rash can be reduced by slow titration of 25mg every other day for the first week and 25mg per day for the second week. Rare hypersensitivity reactions, e.g. Stevens-Johnson syndrome, remain a problem. The risk-benefit ratio of felbamate has recently been compromised by fatal aplastic anaemia and fatal liver disease in a number of patients. In general, patients should be withdrawn from felbamate, if possible, until further clarification of its definitive risk-benefit ratio. Finally, gabapentin is a very safe add-on medication. Its remarkably low potential to cause adverse effects makes it a welcome addition for the treatment of refractory partial epilepsy.
Schmidt
D
D
Epilepsy Research Group, Berlin, Germany.
Krämer
G
G
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control; D000741:Anemia, Aplastic / Q000139:chemically induced / Q000517:prevention & control; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D004342:Drug Hypersensitivity / Q000517:prevention & control; D004827:Epilepsy / Q000188:drug therapy; D000078328:Felbamate; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008107:Liver Diseases / Q000517:prevention & control; D001523:Mental Disorders / Q000139:chemically induced / Q000517:prevention & control; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D000077213:Lamotrigine; D000078328:Felbamate