Phenytoin increases the clearance of
busulfan and reduces its AUC by about 20%. Subtherapeutic levels of
phenytoin may occur in the presence of
busulfan.
The changes in
busulfan clearance are relatively small, but nevertheless it has been suggested that
phenytoin should be avoided in patients taking
busulfan. Note that the US manufacturer of
parenteral busulfan gives a dose assuming that
phenytoin will also be given, and notes that if other antiepileptics are used instead, the
busulfan plasma levels may be increased and monitoring is recommended. If both drugs are given monitor closely to ensure that
busulfan remains effective, and that
phenytoin levels remain therapeutic.