Endocrinologic and Metabolic Advisory Committee
Food and Drug Administration: Center for Drug Evaluation and Research
Bethesda Holiday Inn, 8120 Wisconsin Avenue, Bethesda MD
1. The sponsor proposes an indication, based upon an expectation of cardiovascular benefit, for the use of pravastatin 10 mg in individuals with TC 200-240 mg/dL and LDL-C > 130 mg/dL, regardless of HDL-C level, and without CHD or diabetes. Current guidelines for the treatment of hypercholesterolemia do not target such individuals for drug treatment. Based on the data submitted in the NDA, has the sponsor adequately demonstrated a clinical benefit of pravastatin 10 mg in the target population?
2. Statins have been associated with myopathy, including rare cases of rhabdomyolysis, as well as with elevations in hepatic transaminases (although the association between use of these drugs and serious hepatic disease is less clear). Intercurrent illness, undefined individual susceptibility factors, and interactions with other drugs and/or foods may increase the risk for rhabdomyolysis with statins. Taking into account these and other safety issues, has the sponsor presented adequate data to support the safety of pravastatin 10 mg in the target population?
a. If no, what additional data are needed to demonstrate safety?
3. Taking into consideration the balance of risk and benefit, has the sponsor presented data that are adequate to support the use of pravastatin 10 mg in the low-risk population with TC 200-240 mg/dL, LDL-C > 130 mg/dL, regardless of HDL-C level, without CHD or diabetes?
4. Assuming an indication for the use of pravastatin 10 mg in the proposed target population can be justified based upon an expectation of clinical benefit, has the sponsor adequately demonstrated that consumers can achieve such a clinical benefit in an OTC setting? In responding to this question, please consider the following:
5. Assuming that pravastatin 10 mg is deemed adequately safe when used for the proposed indication in the target population, has the sponsor presented adequate evidence that consumers will be able to use pravastatin 10 mg safely in an OTC setting? In responding to this question, please consider the following:
6. Assuming that the answer to Question 3 is yes (i.e., the sponsor has provided sufficient information to support the safety and effectiveness of pravastatin 10 mg for the proposed indication in the target population), has the sponsor provided sufficient evidence that pravastatin 10 mg can be used safely and effectively in an OTC setting?