Renal Toxicity

In the bone metastases trials, renal deterioration was defined as an increase of 0.5 mg/dL for patients with normal baseline creatinine (<1.4 mg/dL) or an increase of 1.0 mg/dL for patients with an abnormal baseline creatinine (≥1.4 mg/dL). The following are data on the incidence of renal deterioration in patients receiving Zometa 4 mg over 15 minutes in these trials (see Table 9).

The risk of deterioration in renal function appeared to be related to time on study, whether patients were receiving Zometa (4 mg over 15 minutes), placebo, or pamidronate.

In the trials and in postmarketing experience, renal deterioration, progression to renal failure and dialysis have occurred in patients with normal and abnormal baseline renal function, including patients treated with 4 mg infused over a 15-minute period. There have been instances of this occurring after the initial Zometa dose.

Table 3: Percentage of Patients with Adverse Events ≥10% Reported in Hypercalcemia of Malignancy Clinical Trials by Body System  Zometa  Pamidronate 
 4 mg  90 mg 
 n (%)  n (%) 
Patients Studied     
Total No. of Patients Studied 86 (100) 103 (100)
Total No. of Patients with any AE 81 (94) 95 (92)
Body as a Whole     
Fever 38 (44) 34 (33)
Progression of Cancer 14 (16) 21 (20)
Cardiovascular     
Hypotension 9 (11) 2 (2)
Digestive     
Nausea 25 (29) 28 (27)
Constipation 23 (27) 13 (13)
Diarrhea 15 (17) 17 (17)
Abdominal Pain 14 (16) 13 (13)
Vomiting 12 (14) 17 (17)
Anorexia 8 (9) 14 (14)
Hemic and Lymphatic System     
Anemia 19 (22) 18 (18)
Infections     
Moniliasis 10 (12) 4 (4)
Laboratory Abnormalities     
Hypophosphatemia 11 (13) 2 (2)
Hypokalemia 10 (12) 16 (16)
Hypomagnesemia 9 (11) 5 (5)
Musculoskeletal     
Skeletal Pain 10 (12) 10 (10)
Nervous     
Insomnia 13 (15) 10 (10)
Anxiety 12 (14) 8 (8)
Confusion 11 (13) 13 (13)
Agitation 11 (13) 8 (8)
Respiratory     
Dyspnea 19 (22) 20 (19)
Coughing 10 (12) 12 (12)
Urogenital     
Urinary Tract Infection 12 (14) 15 (15)
Table 4: Grade 3 Laboratory Abnormalities for Serum Creatinine, Serum Calcium, Serum Phosphorus, and Serum Magnesium in Two Clinical Trials in Patients with HCM  Grade 3 
Laboratory Parameter  Zometa  Pamidronate 
 4 mg  90 mg 
 n/N  (%)  n/N  (%) 
Serum Creatinine1  2/86 (2%) 3/100 (3%)
Hypocalcemia2  1/86 (1%) 2/100 (2%)
Hypophosphatemia3  36/70 (51%) 27/81 (33%)
Hypomagnesemia4  0/71 — 0/84 —
Table 5: Grade 4 Laboratory Abnormalities for Serum Creatinine, Serum Calcium, Serum Phosphorus, and Serum Magnesium in Two Clinical Trials in Patients with HCM  Grade 4 
Laboratory Parameter  Zometa  Pamidronate 
 4 mg  90 mg 
 n/N  (%)  n/N  (%) 
Serum Creatini