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sNDA 21-386, Zometa Safety Review

sNDA 21-386, Zometa Safety Review. Nancy S. Scher, M.D. Oncology Drug Products CDER, FDA. Protocol Amendments Affecting Safety. Changes in infusion (June 1999) infusion time increased from 5 to 15 minutes infusion volume increased from 50 to 100 ml Dose reduced for 8 mg arm (June 2000)

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sNDA 21-386, Zometa Safety Review

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  1. sNDA 21-386, ZometaSafety Review Nancy S. Scher, M.D. Oncology Drug Products CDER, FDA

  2. Protocol Amendments Affecting Safety • Changes in infusion (June 1999) • infusion time increased from 5 to 15 minutes • infusion volume increased from 50 to 100 ml • Dose reduced for 8 mg arm (June 2000) • subsequent doses were 4 mg (8/4 mg group) • Creatinine monitoring required (June 2000) • Assess prior to each dose • Hold Zometa for renal deterioration • Resume if creatinine within 10% of baseline

  3. Renal Deterioration by Baseline Creatinine15-Minute Infusion, Study 010, Breast and Myeloma

  4. Summary of SafetyStudy 010 (Zometa 4 vs. Aredia) • Incidence of adverse events similar • More patients with >25% decrease in Hb • Higher incidence of Zometa renal function deterioration before 15-minute amendment • Incidence of renal function deterioration similar post amendment • Time to first renal deterioration similar

  5. Renal Deterioration by Baseline Creatinine15-Minute Infusion, Study 039, Prostate

  6. Renal Deterioration by Baseline Creatinine15 Minute Infusion, Study 011, Solid Tumors

  7. Summary of SafetyStudies 039 and 011 • More bisphosphonate-associated AEs for Zometa than placebo • fever, arthralgias, electrolyte abnormalities • Anemia more common for Zometa • Increased incidence of renal function deterioration for Zometa • related to duration of therapy

  8. Safety Conclusions • Administration and dosage • 4 mg i.v. over 15 minutes • Q 3-4 weeks • Acceptable safety profile • more toxic than placebo (039 and 011) • similar to Aredia 90 mg i.v. over 2 hours (010) • Caution: Renal issues • trials excluded creatinine > 3 mg/dL • renal excretion • monitor serum creatinine all patients

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