Drug Interaction Report

GENERALLY AVOID: Coadministration of clofarabine with other nephrotoxic agents may increase the risk of renal impairment due to additive effects on the kidney. Moreover, renal impairment secondary to the use of these agents may reduce the clearance of clofarabine, which is primarily eliminated by renal excretion. This may increase the risk of other adverse effects such as nausea, vomiting, stomatitis, hypertension, hypotension, myelosuppression, hemorrhage, and hepatotoxicity. In clinical trials for clofarabine, grade 3 or 4 elevations in creatinine occurred in 8% of patients, and acute renal failure was reported in 3% at grade 3 and 2% at grade 4. Hematuria was observed in 13% of patients overall. Patients with infection, sepsis, or tumor lysis syndrome may be at increased risk of renal toxicity during treatment with clofarabine.

MANAGEMENT: Drugs that are potentially nephrotoxic (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; aminosalicylates; antiviral/antiretroviral agents such as acyclovir, adefovir, cidofovir, foscarnet, ganciclovir, and tenofovir; antineoplastics such as aldesleukin, carboplatin, cisplatin, ifosfamide, streptozocin, and high intravenous dosages of methotrexate; chelating agents such as deferasirox, deferoxamine, edetate disodium, and edetate calcium disodium; immunosuppressants such as cyclosporine, everolimus, sirolimus, and tacrolimus; intravenous bisphosphonates; intravenous pentamidine; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents; gallium nitrate; lithium; penicillamine) should be avoided during the 5 days of clofarabine administration if possible. Renal function should be evaluated prior to and during therapy, and administration discontinued immediately if substantial increases (e.g., grade 3 or higher) in creatinine are noted. Clofarabine therapy should be reinstated when the patient is stable and renal function has returned to baseline, generally with a 25% dose reduction.