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?