Drug Interactions between Duzallo and thiotepa

MONITOR: Coadministration of allopurinol with cytotoxic agents in patients with neoplastic disease, other than leukemia, may increase the risk of myelosuppressive side effects. Allopurinol therapy alone has been associated with myelosuppressive adverse reactions (e.g., anemia, leukopenia and/or thrombocytopenia). Theoretically, combination with cytotoxic agents may increase this risk, however, data are conflicting. In a well-controlled study of patients on allopurinol who received cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine (mustine HCl), increases in toxic reactions of the cytotoxic agents were not observed.

MANAGEMENT: Caution as well as closer clinical and laboratory monitoring for the development of myelosuppression are advised when allopurinol is used concomitantly with cytotoxic agents.

MONITOR: Coadministration with CYP450 3A4 and/or 2B6 inducers may decrease plasma concentrations of thiotepa and increase concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by these isoenzymes. In a study involving a 42-year-old male with relapsing germ-cell cancer, the pharmacokinetics of thiotepa and its active metabolite (TEPA) were assessed during two high-dose chemotherapy courses (cyclophosphamide 1500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin), with phenytoin initiated five days before the second course for seizure management. In the second course, TEPA exposure increased by 115% and thiotepa exposure decreased by 29%, resulting in a thiotepa dose reduction of nearly 40% on day 3 due to the increased risk of toxicity from higher TEPA exposure. Clinical data for thiotepa use in combination with other less potent CYP450 3A4 inducers or with CYP450 2B6 inducers are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects is advised when thiotepa is used concurrently with CYP450 3A4 and/or 2B6 inducers. Patients should be more closely monitored for thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity. A dosage reduction of thiotepa may be necessary. Pretreatment and subsequent blood counts may be used to guide dose adjustments in accordance with product labeling.