Drug Interactions between cyclosporine and Thioplex

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration of thiotepa with tacrolimus or cyclosporine may potentiate the risk of severe immunosuppression or lymphoproliferation. Serious and fatal infections, as well as myelosuppression, including neutropenia, thrombocytopenia, and anemia have been reported with the use of thiotepa. Additionally, lymphoproliferative disorders are a known risk during treatment with tacrolimus and cyclosporine. Concomitant use may potentiate these risks, although clinical studies are not currently available. Cyclosporine is also a CYP450 3A4 inhibitor which may increase plasma concentrations of thiotepa and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by CYP450 3A4 and 2B6 isoenzymes. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP450 3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure.

MANAGEMENT: Patients receiving thiotepa concomitantly with tacrolimus or cyclosporine should be monitored closely for the development of signs and symptoms of infection or lymphoproliferation. Additionally, if cyclosporine is coadministered with thiotepa, patients should be monitored for decreased efficacy of thiotepa and increased thiotepa-related adverse effects such as myelosuppression, cutaneous toxicity, and neurotoxicity. The manufacturers' recommendations and institutional protocols for dosage, treatment regimens, monitoring, and management of toxicities should be consulted.