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Hypocalcemia and Azotemia Associated with Zoledronic Acid and Interferon Alfa

Senior Fellow, Division of Hematology/Oncology, Loyola University Stritch School of Medicine, May-wood, IL

Abdul M Choudhury, MD

Assistant Professor, Division of Hematology/Oncology, Loyola University Stritch School of Medicine; Hines Veteran Affairs Medical Center, Hines, IL

Reprints: Tawee Tanvetyanon MD, Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153-3304, fax 708/327-3326, ttanve{at}lumc.edu

OBJECTIVE: To describe severe hypocalcemia and acute renal failure associated with zoledronic acid and interferon alfa in a patient with metastatic carcinoid tumors.

CASE SUMMARY: A 39-year-old white man with metastatic carcinoid tumor tolerated treatment with subcutaneous long-acting octreotide monthly and interferon alfa 6 million units 3 times weekly for 6 months. Due to multiple bony metastases, zoledronic acid was prescribed as a monthly 4-mg intravenous infusion over 30 minutes to prevent skeletal-related events. Although the first infusion went well, the patient developed severe hypocalcemia and acute renal failure after the second zoledronic infusion.

DISCUSSION: Bisphosphonates may infrequently cause symptomatic hypocalcemia, especially among patients who have vitamin D deficiency or hypoparathyroidism or receive treatment with an aminoglycoside. Our literature review suggests that zoledronic acid and interferon alfa may exert additive effects on the inhibition of osteoclasts, thus potentially precipitating hypocalcemia. Renal dysfunction may not be a direct consequence of interferon alfa. However, altered mental function due to hypocalcemia may lead to dehydration and further exacerbate renal dysfunction, a known adverse effect of zoledronic acid. Since therapeutic indications of both interferon alfa and zoledronic acid continue to expand, clinicians should be aware of these serious adverse reactions and potential interaction. Supportive treatment with hydration, calcium supplement, and oral calcitriol resulted in resolution of hypocalcemia, but only partial improvement of azotemia.

CONCLUSIONS: In our patient with metastatic carcinoid tumor, treatment with zoledronic acid and interferon alfa was associated with symptomatic hypocalcemia and acute renal failure.

Key Words: azotemia, hypocalcemia, interferon alfa, zoledronate, zoledronic acid

Published Online, January 23, 2004. www.theannals.com, DOI 10.1345/aph.1D357

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