Severe Hypocalcemia Due To Denosumab In Metastatic Prostate Cancer

1277 words - 5 pages

Hypocalcemia is a rare and dangerous side effect of the drug Denosumab. We present a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug. A total of 80 gm of intravenous and 370 gm of oral calcium were administered in vain and a maximum ionized calcium level attained was 0.71mmol/ during the first 16 days of hospital stay. Due to worsening renal failure from tumor spread our patient needed dialysis to achieve normal calcium levels. Checking calcium and Vitamin D levels prior to administration of Denosumab is very vital in preventing this adverse outcome. By presenting this case we emphasize on the importance of checking Vitamin D levels prior to administration of the drug and also make other clinicians aware of a potential severe life threatening electrolyte imbalance.

Denosumab is a fully human monoclonal antibody, administered subcutaneously, that inhibits osteoclast mediated bone resorption in bone metastases from solid tumors and multiple myeloma. See Fig A below for details.

A 45-year-old gentleman with a 3-year history of metastatic (bone, liver & lymph nodes) prostate cancer and Hypertension presented to the hospital with worsening leg swelling and hematuria. He had been treated with androgen deprivation therapy in the past, along with 3 doses of zoledronic acid for bone metastases. The bone pains were not controlled with the above regimen and hence he was switched to Denosumab. Vitals at admission were within normal limits except Blood pressure of 160/90 mmHg. Pertinent findings on physical examination were the presence of bilateral lower extremity edema and negative Chvostek and Trousseaus’s signs. Review of symptoms was positive for hematuria and leg swelling. The Electrocardiogram was consistent with a prolonged QT interval. Laboratory studies revealed a sodium of 135 mEq/L, Potassium of 4.9 mEq/L, Chloride of 105 mEq/L, Bicarbonate of 23 mEq/L, Blood urea Nitrogen of 22 mg/dl, Creatinine of 1.34 mg/dL, Glucose of 133 mg/dL and a Calcium of 4.5 mg/dl, with Ionised calcium at admission being 0.58mmol/L. Patient received a dose of Denosumab thirteen days prior to presentation as an outpatient. Prior to Denosumab administration, serum calcium was 8.4 mg/dl with an albumin of 2.9 g/dl. His vitamin D levels had not been checked prior to administration of Denosumab. After admission his vitamin D 25-OH level was low at 12.1 ng/ml, vitamin D 1,25 dihydroxy level was high at 95.4 pg/ml. His initial PTH levels were high at 440.7pg/ml.

He was started on ergocalciferol, calcitriol and high doses of intravenous and oral calcium supplementation. Over the next 16 days he received 80 gm of intravenous calcium gluconate, 370 gm of oral calcium but the highest ionized calcium level achieved was 0.71 mmol/L. The graphs below show the calcium levels and ionized calcium levels during the hospital while getting oral and intravenous calcium supplementation.

He continued to have...

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