Lanthanum carbonate: safety data after 10 years

Area of Science:

• Nephrology and Pharmacology
• Mineral Metabolism and Drug Safety

Background:

• Persistent concerns exist regarding lanthanum carbonate's potential for aluminum-like accumulation and toxicity, despite 10 years of post-marketing surveillance.
• Understanding the distinct pharmacokinetic profiles of lanthanum and aluminum is crucial for assessing lanthanum carbonate's safety.

Purpose of the Study:

• To provide a comprehensive overview of lanthanum carbonate's safety profile.
• To present interim findings from a 5-year observational database study (SPD405-404) evaluating lanthanum carbonate safety in end-stage renal disease (ESRD) patients.

Main Methods:

• Review of pharmacokinetic data comparing lanthanum and aluminum absorption and elimination pathways.
• Analysis of randomized prospective studies with paired bone biopsies to assess lanthanum accumulation and toxicity.
• Interim analysis of the 5-year observational study (SPD405-404) using Kaplan-Meier survival estimates and fracture rate data from the US Renal Data System.

Main Results:

• Lanthanum is minimally absorbed and hepatobiliary eliminated, unlike aluminum which is renally eliminated.
• Bone biopsies showed no lanthanum accumulation or toxicity; no clinically relevant changes in liver enzymes or bilirubin were observed with up to 6 years of treatment.
• Interim 5-year survival rates: 51.6 months for lanthanum carbonate, 48.9 months for other phosphate binders, and 40.3 months for historical controls. Bone fracture rates were comparable across groups (5.9-6.7%).

Conclusions:

• Lanthanum carbonate demonstrates a favorable safety profile with no evidence of aluminum-like toxicity or accumulation.
• Extensive worldwide patient exposure (over 850,000 person-years) supports the safety of lanthanum carbonate in ESRD patients.
• Lanthanum carbonate is not associated with adverse safety outcomes, including concerning effects on bone, liver, or survival rates.