Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

No interaction of treosulfan was observed in high-dose chemotherapy.
Detailed in vitro studies did not completely exclude potential interactions between high plasma concentrations of treosulfan and CYP3A4, CYP2C19, or P-glycoprotein (P-gp) substrates.
Physiologically-based pharmacokinetic modelling predicted a weak
(AUC ratio ≥ 1.25 and < 2) to moderate (AUC ratio ≥ 2 and < 5) interaction for CYP3A4, a weak interaction for CYP2C19, and a negligible (AUC ratio < 1.25) interaction for P-gp.
Therefore, medicinal products with a narrow therapeutic index (e.g. digoxin) that are substrates for CYP3A4 or CYP2C19 should not be given during treatment with treosulfan.

Considering overall timing of treatments and the respective pharmacokinetic properties of concomitantly used medicinal products (e.g. half-life), the interaction potential can be reduced to “no interaction” (AUC ratio < 1.25), if all concomitantly used medicinal products are dosed 2 hours before or 8 hours after the 2-hour intravenous infusion of treosulfan.

The effect of treosulfan on the pharmacokinetics of fludarabine is not known.