Etoposide clearance appears to be increased by phenobarbital,phenytoin,and probably carbamazepine, and this may result inreduced efficacy.
Clinical evidence,mechanism, importance and management
The clearance of etoposide was found to be highly variable in children given etoposide 320 to 500 mg/m(See reference number 2) over 6 hrs on alternate days for a total of 3 doses. However,it was 77 % higher in 7 children taking antiepileptics (phenobarbital, phenytoin or both) than in 22 others not taking antiepileptics (See reference number 1). In a retrospective survey,long-term antiepileptic use (phenytoin, phenobarbital, carbamazepine, or a combination) was associated with worse event-free survival, and greater haematological and/or CNS relapse in children receiving chemotherapy for B-lineage acute lymphoblastic leukaemia. The authors considered that increased clearance of etoposide induced by antiepileptics was a likely factor in these findings (See reference number 2). Be alert for possible need to give larger doses of etoposide if these antiepileptics are used. More study is needed.
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