Questions for Consideration of the Joint Meeting

Nonprescription Drugs Advisory Committee &

Endocrinologic and Metabolic Advisory Committee

 

July 14, 2000

 

 

Food and Drug Administration: Center for Drug Evaluation and Research

Bethesda Holiday Inn, 8120 Wisconsin Avenue, Bethesda MD

 

Pravachol NDA 21-198, Bristol Myers Squibb

 

 

Efficacy and Safety in the Proposed Target Population

 

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?

  1. If yes, what is the nature and magnitude of the benefit?
  2. If no, what additional data are needed to demonstrate a clinical benefit 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?

  1. If no, what additional data are needed to support such an indication?

 

OTC Considerations

 

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:

  1. The ability of consumers to appropriately self-select (and de-select) based upon cholesterol levels and other risk factors.
  2. The ability of consumers to evaluate response to treatment and to monitor cholesterol levels (including understanding of how to undertake a fast and the frequency of re-testing).
  3. The ability of consumers to adhere to chronic therapy with pravastatin 10 mg.
  4. The need for the physician or other healthcare professional in the effective treatment and follow up of dyslipidemia.
  5. The capacity of the proposed label to direct consumers in the effective use of pravastatin 10 mg OTC.

 

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:

  1. The ability of the consumer to identify adverse reactions to pravastatin and to act appropriately.
  2. The ability of the consumer to monitor hepatic safety including the need for monitoring of hepatic transaminases and the ability of the consumer to perform such monitoring if needed.
  3. The need for and ability of the consumer to identify and avoid interacting drugs and other substances.
  4. The likelihood of use of pravastatin 10 mg at higher than recommended doses (1 tablet per day).
  5. The ability of women who are pregnant or likely to become so to appropriately avoid use of pravastatin 10 mg.
  6. The need for the physician or other healthcare professional in the safe treatment and follow up of dyslipidemia.
  7. The capacity of the proposed label to direct consumers in the safe use of pravastatin 10 mg OTC.

 

Approvability

 

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?

  1. If yes, are any additional studies needed post-approval? What are the key messages that need to be conveyed to the consumer in the product label (carton and package insert) to provide for the safe and effective use of pravastatin 10 mg OTC?
  2. If no, what additional studies are necessary to support approval for OTC marketing?