In the breast cancer and myeloma trial, efficacy was determined by a noninferiority analysis comparing Zometa to pamidronate 90mg for the proportion of patients with a SRE. This analysis required an estimation of pamidronate efficacy. Historical data from 1,128patients in three pamidronate placebo-controlled trials demonstrated that pamidronate decreased the proportion of patients with a SRE by13.1% (95%CI=7.3%, 18.9%). Results of the comparison of treatment with Zometa compared to pamidronate are given in Table14.

Table 14: Zometa Compared to Pamidronate in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer  I. Analysis of Proportion of Patients with a SRE1 II. Analysis of Time to the First SRE
Study Study Arm &
Patient Number Proportion Difference2
& 95% CI P-value Median
(Days) Hazard Ratio3
& 95% CI P-value
Multiple Myeloma
& Breast Cancer Zometa 4mg
(n=561)
Pamidronate
(n=555) 44%
46% -2%
(-7.9%, 3.7%) 0.46 373
363 0.92
(0.77, 1.09) 0.32
1SRE=Skeletal-Related Event
2Difference for the proportion of patients with a SRE of Zometa 4mg versus pamidronate 90mg.
3Hazard ratio for the first occurrence of a SRE of Zometa 4mg versus pamidronate 90mg.

16HOW SUPPLIED/STORAGE AND HANDLING
4 mg/100 mL single-use ready-to-use bottle

Carton of 1 bottle……………………………………………………………………………...NDC0078-0590-61

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

4 mg/5 mL single-use vial of concentrate

Carton of 1 vial……………………………………………………………………………..NDC0078-0387-25

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

17PATIENT COUNSELING INFORMATION
Patients should be instructed to tell their doctor if they have kidney problems before being given Zometa.

Patients should be informed of the importance of getting their blood tests (serum creatinine) during the course of their Zometa therapy.

Zometa should not be given if the patient is pregnant or plans to become pregnant, or if she is breast-feeding.

Patients should be advised to have a dental examination prior to treatment with Zometa and should avoid invasive dental procedures during treatment.

Patients should be informed of the importance of good dental hygiene and routine dental care.

Patients with multiple myeloma and bone metastasis of solid tumors should be advised to take an oral calcium supplement of 500mg and a multiple vitamin containing 400IU of VitaminD daily.

Patients should be aware of the most common side effects including: anemia, nausea, vomiting, c