a of malignancy (HCM) who received either Zometa 4mg given as a 5-minute intravenous infusion (n=86) or pamidronate 90mg given as a 2-hour intravenous infusion (n=103). The population was aged 33-84 years, 60%male and 81%Caucasian, with breast, lung, head and neck, and renal cancer as the most common forms of malignancy. NOTE: pamidronate 90mg was given as a 2-hour intravenous infusion. The relative safety of pamidronate 90mg given as a 2-hour intravenous infusion compared to the same dose given as a 24-hour intravenous infusion has not been adequately studied in controlled clinical trials.
Renal Toxicity
Administration of Zometa 4mg given as a 5-minute intravenous infusion has been shown to result in an increased risk of renal toxicity, as measured by increases in serum creatinine, which can progress to renal failure. The incidence of renal toxicity and renal failure has been shown to be reduced when Zometa 4mg is given as a 15-minute intravenous infusion. Zometa should be administered by intravenous infusion over no less than 15minutes [see Warnings And Precautions(5) and Dosage And Administration(2)].
The most frequently observed adverse events were fever, nausea, constipation, anemia, and dyspnea (seeTable4).
Table4 provides adverse events that were reported by 10% or more of the 189patients treated with Zometa 4mg or Pamidronate 90mg from the two HCM trials. Adverse events are listed regardless of presumed causality to study drug.
Table 4: Percentage of Patients with Adverse Events ≥10% Reported in Hypercalcemia of Malignancy Clinical Trials by Body System Zometa Pamidronate
4mg 90mg
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)
The following adverse events from the two controlled multicenter HCM trials (n=189) were reported by a greater percentage of patients treated with Zometa 4mg than with pamidronate 90mg and occurred with a frequency of greater than or equal to 5% but less than 10%. Adverse events are listed regardless of presumed causality to study drug: Asthenia, chest pain, leg edema, mucositis, dysphagia, granulocytopenia, thrombocytopenia, pancytopenia, nonspecific infection, hypocalcemia, dehydration, arthralgias, headache and somnolence.
Rare cases of rash, pruritus, and ch
