Drug Interaction Report

GENERALLY AVOID: Oral bioavailability and systemic exposure of cladribine may be increased by potent inhibitors of breast cancer resistance protein (BCRP) while intracellular distribution and renal elimination of cladribine may be altered by potent inhibitors of equilibrative nucleoside transporter 1 (ENT1) and concentrative nucleoside transporter 3 (CNT3). The mechanism involves inhibition of ENT1, CNT3, and/or BCRP as cladribine is a substrate of each of these transporter systems. The clinical relevance remains unknown.

MANAGEMENT: Coadministration of potent ENT1, CNT3, or BCRP transporter inhibitors should be avoided during the 4 to 5-day oral cladribine treatment cycles. If coadministration is required, consider concomitant alternatives that exhibit no or minimal inhibition of ENT1, CNT3, or BCRP. If this is not possible, dose reduction to the minimum mandatory dose, separation in the timing of administration, and careful patient monitoring is recommended.

ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions. Cladribine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility. The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.