Busulfex Drug Interactions

No specific clinical trial was carried out to assess drug-drug interaction between intravenous busulfan and itraconazole or metronidazole. From published studies in adults, administration of itraconazole to patients receiving high-dose busulfan may result in reduced busulfan clearance. Also, there are published case reports of increased plasma levels of busulfan after administration of metronidazole. Patients who are concurrently treated with busulfan and itraconazole or metronidazole should be closely monitored for signs of busulfan toxicity.
No interaction was observed when busulfan was combined with fluconazole (antifungal agent). Published studies in adults described that ketobemidone (analgesic) might be associated with high levels of plasma busulfan. Therefore special care is recommended when combining these two compounds. In adults, for the BuCy2 regimen it has been reported that the time interval between the last oral busulfan administration and the first cyclophosphamide administration may influence the development of toxicities. A reduced incidence of Hepatic Veno Occlusive Disease (HVOD) and other regimen related toxicity have been observed in patients when the lag time between the last dose of oral busulfan and the first dose of cyclophosphamide is > 24 hours. There is no common metabolism pathway between busulfan and fludarabine.
In adults, for the FB regimen, published studies did not report any mutual drug-drug interaction between intravenous busulfan and fludarabine.
Paracetamol is described to decrease glutathione levels in blood and tissues, and may therefore decrease busulfan clearance when used in combination (see Precautions).
Either phenytoin or benzodiazepines were administered for seizure prophylaxis in patients participating to the clinical trials conducted with intravenous busulfan (see Dosage & Administration and Precautions). The concomitant systemic administration of phenytoin to patients receiving high-dose of oral busulfan has been reported to increase busulfan clearance, due to induction of glutathion-S-transferase whereas no interaction has been reported when benzodiazepines such as diazepam, clonazepam or lorazepam have been used to prevent seizures with high-dose busulfan.
No evidence of an induction effect of phenytoin has been seen on Busulfex data. A phase II clinical trial was performed to evaluate the influence of seizure prophylaxis treatment on intravenous busulfan pharmacokinetics. In this study, 24 adult patients received clonazepam (0.025-0.03 mg/kg/day as IV continuous infusions) as anticonvulsant therapy and the PK data of these patients were compared to historical data collected in patients treated with phenytoin. The analysis of data through a population pharmacokinetic method indicated no difference on intravenous busulfan clearance between phenytoin and clonazepam based therapy and therefore similar busulfan plasma exposures were achieved whatever the type of seizure prophylaxis.
No interaction was observed when busulfan was combined with 5 HT3 antiemetics such as ondansetron or granisetron.
Increases in busulfan exposure have been observed at concomitant administration of busulfan and deferasirox. The mechanism behind the interaction is not fully elucidated. It is recommended to regularly monitor busulfan plasma concentrations and, if necessary, adjust the busulfan dose in patients who are or have recently been treated with deferasirox.