The Serious Public Health Dangers of Prescription-to-OTC Switch of Lovastatin (HRG Publication #1719)
January 14, 2005 Testimony of Sidney M. Wolfe, M.D. Before FDA Endocrinologic/Metabolic and Non-Prescription Drugs Advisory Committees
In testimony before the FDA in June, 2000 concerning general switching principles for any drug, I discussed several prerequisites for the safe and effective switching of drugs from prescription to OTC status. They included:
If any one of these criteria is not met, the decision to switch a drug to OTC is wrong from an overall public health perspective. If none of the conditions are met, the switch is likely to be an even greater public health disaster, having an overall negative effect on health. For the switch of any statin, in this case lovastatin, none of the conditions are met and it is virtually certain that more harm than benefit would accrue to such an ill-advised regulatory decision. Despite Merck and its highly-paid academic partners’ efforts to paint this switch as something positive, the analysis by FDA, with which I concur, seriously undermines any such conclusion.
1. Ease/possibility of accurate self-diagnosis. Since the proposed use is primary prevention in people without symptoms, the correct assessment relies entirely on lab tests and the assessment of other risk factors. The data from Merck’s studies of label comprehension and, separately, the actual use of lovastatin---despite the misleadingly positive spin by Merck---yield unacceptable results as far as the ability of very many patients to accurately assess all of the factors necessary to qualify as a candidate for OTC use of lovastatin.
2. Benefit/risk ratio, its continued evaluation and adverse drug reactions or interactions and the ease of detecting them. The continued evaluation of benefit and risk depends in part on the follow-up cholesterol levels to see if the drug is working and many patients did not have follow-up cholesterol levels. Among the adverse drug reactions that may be difficult to detect, in the absence of physician involvement in a prescription for this drug, and thereby intervene are asymptomatic elevations in liver enzymes after taking lovastatin and asymptomatic liver disease before using the drug. The onset of myositis (muscle inflammation), a possible predecessor to life-threatening rhabdomyolyis, may not alert the patient who is not necessarily under the supervision of a physician that reduction of dose or cessation of therapy may be necessary. A recent large case-control study from Italy has found a significant excess of peripheral nerve damage in patients using statins which the authors cautiously describe as hypothesis-generating that will have to be followed up with further investigation. The possible connection between this kind of problem and statin use may not be perceived by patients. (Lipid lowering drug prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated data bases. J Epidemiol Community Health 2004;58:1047-1051)
Summary: Since, as is the case for a substantial percentage of those choosing to use the OTC version of this drug, their risk for CHD is so low that there is no evidence they will benefit from the drug, they are being subjected to the various risks of adverse reactions without any possibility of benefit. Thus the risks clearly outweigh the benefits for this group. These appalling results showing massive, incorrect self-selection for using this drug alone should prevent approval. In addition, it is clear that the availability of easy-to-get OTC statins will deter many from safer, less expensive preventive measures. Prevention of cardiovascular disease must be a multi-pronged strategy to reduce risk. The use of heavily advertised statins, out of the context of medical consultation, may impair the development of an integrated long-term strategy for preventing strokes or heart attacks. Diet and exercise, critically important components, may be thought to be less important if the primary strategy seems to be a statin drug.
The safety problems, although somewhat rare for statins other than Crestor, are especially hard to detect and monitor without physician involvement and, as mentioned above, must be viewed as unacceptable for the large proportion of people who can not possibly benefit from the drugs. Even for those who might theoretically benefit, the small fraction who self-selected properly, there is a serious question as to whether the 20 milligram dose confers any clinical benefit. In the FDA statistician’s summary, there is a quote from Merck stating that because ½ the patients were titrated to the 40 mg dose [twice the OTC dose of 20 mg]…. In fact the applicant [Merck] stated that because of the titration, “direct estimation of the benefit of 20 mg … is not possible” (page D-61 of the NDA). As was the case in 2000, your advisory committees and the FDA should promptly reject this application.